Genus Litophyton: A Hidden Treasure Trove of Structurally Unique and Diversely Bioactive Secondary Metabolites

Marine soft corals are prolific sources of various natural products that have served as a wealthy reservoir of diverse chemical scaffolds with potential as new drug leads. The genus Litophyton contains almost 100 species but only a small proportion of them has been chemically investigated, which calls for more attentions from global researchers. In the current work, 175 secondary metabolites have been discussed, drawing from published data spanning almost five decades, up to July 2023. The studied species of the genus Litophyton resided in various tropical and temperate regions and encompassed a broad range of biologically active natural products including terpenes, steroids, nitrogen-containing metabolites, lipids, and other metabolites. A wide spectrum of pharmacological effects of these compounds had been evaluated, such as cytotoxic, antiviral, antibacterial, antifungal, anti-malarial, antifeedant, anti-inflammatory, molluscicidal, PTP1B inhibitory, insect growth inhibitory, and neuroprotective activities. This review aims to offer an up-to-date survey of the literature and provide a comprehensive understanding of the chemical structures, taxonomical distributions, and biological activities of the reported metabolites from the title genus whenever available.


Introduction
More than two-thirds of the Earth's surface is covered by oceans, which harbor a vast array of creatures, including plants, animals, and microbes.Since the ancient times, marine organisms have been used as sources of foods [1], cosmetic ingredients [2], and drugs [3], which are hotspots for global researchers nowadays [4].Continuous studies focused on the secondary metabolites derived from marine environments, resulting in a rapid expansion of marine natural products [5].These substances displayed a wide spectrum of potential pharmacological effects, including antivirus [6], anti-osteoclastogenesis [7], antimicrobial [8], and antitumor [9].To date, almost 20 drugs from marine sources are in clinical use [10].
The marine soft coral genus Litophyton belongs to the family Nephtheidae, order Alcyonacea, subclass Octocorallia.It might be worth pointing out the taxonomic relationship between the genera Nephthea and Litophyton, both of which are in the same family Nephtheidae.In 2016, the genus Nephthea was synonymized with the genus Litophyton due to their identical characteristics in terms of mitochondrial DNA molecular information and morphology (including features such as bone needle, tentacle shape, polyp, and stem) [11,12].Currently, the genus Litophyton consists of nearly 100 species, according to the Word Register of Marine Species (WoRMS) [13].They are widely distributed throughout tropical and temperate waters, such as the South China Sea [14], Red Sea [11], as well as other waters of the Indo-Pacific Ocean [15][16][17].
The alcyonarian Litophyton viridis was observed to provide chemical protection for the fish Abudefduf leucogaster [18].In addition to the ecological role, the extracts of several soft corals of the genus Litophyton have been biologically screened and showed a variety of potent bioactivities, such as antioxidant [19], genotoxic [20], cytotoxic [19,21,22], HIV-1 enzyme inhibitory [21], antibacterial [22], anti-inflammatory [23], antifungal [24], and wound healing [25] activities.Chemical investigations on Litophyton soft corals were carried out by researchers worldwide and revealed that soft corals of the genus Litophyton are prolific producers of bioactive secondary metabolites.However, there was no specific review of compounds isolated from soft corals of the original Litophyton genus.However, a summary of the chemical constituents and biological properties of the synonymized Nephthea genus was reported [26,27], which covered the work published from 1974 to 2010.On the basis of an extensive literature search using SciFinder, this work specifically summarized for the first time all the secondary metabolites isolated from species currently classified within the genus Litophyton, covering a period of near five decades (between 1975 and July 2023) for the original Litophyton species and since 2011 for the synonymized Nephthea species.

Classification of Secondary Metabolites from the Genus Litophyton
Since the early reports of novel cembrane diterpenes from the soft corals Nephthea sp.[28] and L. viridis [29] in the beginning of 1970s, many research groups around the world have carried out chemical investigation of the genus Litophyton, resulting in fruitful achievements.For instance, two uncommon bis-sesquiterpenes, dikelsoenyl ether and linardosinene H, were encountered during the research of two alcyonarians, Nephthea erecta [30] and Litophyton nigrum [31], respectively.Up to July 2023, a total of 175 secondary metabolites have been isolated and characterized in Litophyton corals during almost 50 years of research (Table S1).These chemical compounds can be structurally classified as sesquiterpenes, sesquiterpene dimers, diterpenes, norditerpenes, tetraterpenes, meroterpenes, steroids, ceramides, pyrimidines, peptides, prostaglandins, γ-lactones, fatty acids, glycerol ethers, and selenides.In the following subsections, these compounds were further grouped under different categories based on their structural features.Among them, the ceramides, pyrimidines, and peptides were placed under one category, 'nitrogen-containing metabolites'.The pack of 'lipids' comprise prostaglandins, γ-lactones, fatty acids, and glycerol ethers.Other metabolites include selenides.Herein, the chemical structures, taxonomical distributions, and biological activities of the reported metabolites from the title genus whenever available are described.

Sesquiterpenes
This was a large cluster of terpenes obtained from the genus Litophyton with an account of 38 compounds in this review.These compounds possessed a variety of carbon frameworks, which could be further classified into 14 categories: bicyclogermacrane, secgermacrane, guaiane, pseudoguaiane, himachalene, eudesmane, seco-eudesmane, tri-noreudesmane, eremophilane, nardosinane, nornardosinane, neolemnane, seconeolemnane, and kelsoane (Figure 1).This diversity of skeletons makes sesquiterpenes the most interesting type of natural products from this genus.The different sesquiterpenes were distributed in four species, Litophyton arboreum, L. nigrum, Litophyton setoensis, Nephthea erecta, and an unclearly identified Nephthea sp., which inhabited different marine environments including the Red Sea, South China Sea, and the waters around Indonesia and Taiwan (Table S1).

Bicyclogermacrane Sesquiterpenes
Chemical investigation of the soft coral L. arboreum, which was collected near Bali, Indonesia, yielded the sesquiterpene (−)-bicyclogermacrene (1) [32] (Figure 2).This compound exhibited low antiproliferative activities against the cell lines L-929 and K-562 with GI50 values of 186 and 200 µM, respectively, and low cytotoxic effect against the HeLa cell line with CC50 of 182 µM.

Sec-Germacrane Sesquiterpenes
Very recently, Ahmed et al. [33] carried out chemical investigation of the Red Sea specimen L. arboreum, which was collected at Neweba, Egypt.The acyclic sesquiterpene (2E,6E)-3-isopropyl-6-methyl-10-oxoundeca-2,6-dienal (2) was found from this sample, which possessed a sec-germacrane nucleus (Figure 3).Anti-malarial bioassays disclosed the isolate 2 was active against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC50 values of 3.7 and 2.2 mg/mL, respectively.In addition, the metabolite 2 was non-toxic to the Vero cell line at the concentration of 4.76 mg/mL.These findings demonstrated that sesquiterpene 2 could be developed as an antimalarial lead compound that is highly safe in the range of tested concentrations.

Bicyclogermacrane Sesquiterpenes
Chemical investigation of the soft coral L. arboreum, which was collected near Bali, Indonesia, yielded the sesquiterpene (−)-bicyclogermacrene (1) [32] (Figure 2).This compound exhibited low antiproliferative activities against the cell lines L-929 and K-562 with GI 50 values of 186 and 200 µM, respectively, and low cytotoxic effect against the HeLa cell line with CC 50 of 182 µM.

Bicyclogermacrane Sesquiterpenes
Chemical investigation of the soft coral L. arboreum, which was collected near Bali, Indonesia, yielded the sesquiterpene (−)-bicyclogermacrene (1) [32] (Figure 2).This compound exhibited low antiproliferative activities against the cell lines L-929 and K-562 with GI50 values of 186 and 200 µM, respectively, and low cytotoxic effect against the HeLa cell line with CC50 of 182 µM.

Sec-Germacrane Sesquiterpenes
Very recently, Ahmed et al. [33] carried out chemical investigation of the Red Sea specimen L. arboreum, which was collected at Neweba, Egypt.The acyclic sesquiterpene (2E,6E)-3-isopropyl-6-methyl-10-oxoundeca-2,6-dienal (2) was found from this sample, which possessed a sec-germacrane nucleus (Figure 3).Anti-malarial bioassays disclosed the isolate 2 was active against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC50 values of 3.7 and 2.2 mg/mL, respectively.In addition, the metabolite 2 was non-toxic to the Vero cell line at the concentration of 4.76 mg/mL.These findings demonstrated that sesquiterpene 2 could be developed as an antimalarial lead compound that is highly safe in the range of tested concentrations.

Sec-Germacrane Sesquiterpenes
Very recently, Ahmed et al. [33] carried out chemical investigation of the Red Sea specimen L. arboreum, which was collected at Neweba, Egypt.The acyclic sesquiterpene (2E,6E)-3-isopropyl-6-methyl-10-oxoundeca-2,6-dienal (2) was found from this sample, which possessed a sec-germacrane nucleus (Figure 3).Anti-malarial bioassays disclosed the isolate 2 was active against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC 50 values of 3.7 and 2.2 mg/mL, respectively.In addition, the metabolite 2 was non-toxic to the Vero cell line at the concentration of 4.76 mg/mL.These findings demonstrated that sesquiterpene 2 could be developed as an anti-malarial lead compound that is highly safe in the range of tested concentrations.

Bicyclogermacrane Sesquiterpenes
Chemical investigation of the soft coral L. arboreum, which was collected near Bali, Indonesia, yielded the sesquiterpene (−)-bicyclogermacrene (1) [32] (Figure 2).This compound exhibited low antiproliferative activities against the cell lines L-929 and K-562 with GI50 values of 186 and 200 µM, respectively, and low cytotoxic effect against the HeLa cell line with CC50 of 182 µM.

Sec-Germacrane Sesquiterpenes
Very recently, Ahmed et al. [33] carried out chemical investigation of the Red Sea specimen L. arboreum, which was collected at Neweba, Egypt.The acyclic sesquiterpene (2E,6E)-3-isopropyl-6-methyl-10-oxoundeca-2,6-dienal (2) was found from this sample, which possessed a sec-germacrane nucleus (Figure 3).Anti-malarial bioassays disclosed the isolate 2 was active against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC50 values of 3.7 and 2.2 mg/mL, respectively.In addition, the metabolite 2 was non-toxic to the Vero cell line at the concentration of 4.76 mg/mL.These findings demonstrated that sesquiterpene 2 could be developed as an antimalarial lead compound that is highly safe in the range of tested concentrations.

Guaiane Sesquiterpenes
Interestingly, the guaiane sesquiterpenes were frequently encountered in the Red Sea soft coral L. arboreum.

Pseudoguaiane Sesquiterpenes
A new pseudoguaiane-type sesquiterpene named litopharbol (11) (Figure 5) was isolated from the methanolic extract of the Saudi Arabian Red Sea soft coral L. arboreum by Hawas's group [36].Its structure was determined through the elucidation of NMR data.Compound 11 exhibited a wide spectrum of antibacterial activities against Gram-negative bacteria E. coli ATCC 10536 and P. aeruginosa NTCC 6750, as well as Gram-positive bacteria B. cereus ATCC 9634, B. subtilis ATCC6633, and S. aureus ATCC5141 with MIC values ranging from 1.8 to 9.6 µg/mL.Among these bacteria, 11 showed significant activity against B. cereus ATCC 9634 with an MIC of 1.8 µg/mL.In addition, this sesquiterpene exhibited weak antifungal activities against C. albicans and A. niger with MIC values of 12.5 and 12.9 µg/mL, respectively.Moreover, it displayed cytotoxic effects against cell lines MCF-7, HCT-116, and HepG2 with IC50 values of 9.42, 26.21, and 38.92 µM, respectively.In Hawas's continual study, litopharbdiol (12) was identified, which shared the same carbon framework with 11 [20] (Figure 5).However, no bioassay for this compound was reported in the article.Hawas's group reported the presence of alismol (3) in a Red Sea specimen of L. arboreum collected off the coast of Jeddah, Saudi Arabia, together with another guaiane sesquiterpene alismorientol B (6) [36] (Figure 4).These two secondary metabolites were subjected to antimicrobial and cytotoxic bioassays.As a result, metabolites 3 and 6 showed weak to strong antibacterial activities against Escherichia coli ATCC 10536, Pseudomonas aeruginosa NTCC 6750, Bacillus cereus ATCC 9634, Bacillus subtilis ATCC6633, and Staphylococcus aureus ATCC5141 with MIC values ranging from 10.4 to 1.3 µg/mL.Here, compound 6 had significant activity against B. cereus ATCC 9634 with MIC of 1.3 µg/mL.Compounds 3 and 6 exhibited weak to moderate antifungal activities against Candida albicans and Aspergillus niger with MIC values ranging from 10.1 to 6.0 µg/mL.Moreover, they displayed cytotoxic effects against the cell lines MCF-7, HCT-116, and HepG2, with IC 50 ranging from 4.32 to 44.52 µM.Here, compound 6 showed the most potent cytotoxic effect against MCF-7 cells with IC 50 of 4.32 µM.Additionally, Hawas's group evaluated the methanolic extract of the above-mentioned soft coral for its in vivo genotoxicity and antigenotoxicity against the mutagenicity induced by the anticancer drug cyclophosphamide [20].The extract was found to be safe and nongenotoxic at 100 mg/kg b. wt.Moreover, the mice group of cyclophosphamide pretreated with the extract (100 mg/kg b. wt.) showed significant reduction in the percentage of chromosomal aberrations induced in bone marrow and mouse spermatocytes.

Pseudoguaiane Sesquiterpenes
A new pseudoguaiane-type sesquiterpene named litopharbol (11) (Figure 5) was isolated from the methanolic extract of the Saudi Arabian Red Sea soft coral L. arboreum by Hawas's group [36].Its structure was determined through the elucidation of NMR data.Compound 11 exhibited a wide spectrum of antibacterial activities against Gramnegative bacteria E. coli ATCC 10536 and P. aeruginosa NTCC 6750, as well as Gram-positive bacteria B. cereus ATCC 9634, B. subtilis ATCC6633, and S. aureus ATCC5141 with MIC values ranging from 1.8 to 9.6 µg/mL.Among these bacteria, 11 showed significant activity against B. cereus ATCC 9634 with an MIC of 1.8 µg/mL.In addition, this sesquiterpene exhibited weak antifungal activities against C. albicans and A. niger with MIC values of 12.5 and 12.9 µg/mL, respectively.Moreover, it displayed cytotoxic effects against cell lines MCF-7, HCT-116, and HepG2 with IC 50 values of 9.42, 26.21, and 38.92 µM, respectively.In Hawas's continual study, litopharbdiol (12) was identified, which shared the same carbon framework with 11 [20] (Figure 5).However, no bioassay for this compound was reported in the article.

Pseudoguaiane Sesquiterpenes
A new pseudoguaiane-type sesquiterpene named litopharbol (11) (Figure 5) was isolated from the methanolic extract of the Saudi Arabian Red Sea soft coral L. arboreum by Hawas's group [36].Its structure was determined through the elucidation of NMR data.Compound 11 exhibited a wide spectrum of antibacterial activities against Gram-negative bacteria E. coli ATCC 10536 and P. aeruginosa NTCC 6750, as well as Gram-positive bacteria B. cereus ATCC 9634, B. subtilis ATCC6633, and S. aureus ATCC5141 with MIC values ranging from 1.8 to 9.6 µg/mL.Among these bacteria, 11 showed significant activity against B. cereus ATCC 9634 with an MIC of 1.8 µg/mL.In addition, this sesquiterpene exhibited weak antifungal activities against C. albicans and A. niger with MIC values of 12.5 and 12.9 µg/mL, respectively.Moreover, it displayed cytotoxic effects against cell lines MCF-7, HCT-116, and HepG2 with IC50 values of 9.42, 26.21, and 38.92 µM, respectively.In Hawas's continual study, litopharbdiol (12) was identified, which shared the same carbon framework with 11 [20] (Figure 5).However, no bioassay for this compound was reported in the article.

Himachalene Sesquiterpenes
Purification of the CH2Cl2/MeOH extract of Saudi Arabian Red Sea alcyonarian L. arboreum yielded a new himachalene-type sesquiterpene 3α,6α-epidioxyhimachal-1-ene (13) (Figure 6), which showed antiproliferative effects toward three different cancer cell lines MCF-7, HCT116, and HepG-2 [39].(It might be worth pointing out that no specific data of the bioassay results were provided in this article.)

Tri-Nor-Eudesmane Sesquiterpenes
The methanolic extract of the Saudi Arabia Red Sea L. arboreum collection harbored two tri-nor-eudesmane sesquiterpenes teuhetenone A (16) and calamusin I (17) [36] (Figure 9).Interestingly, these two nor-sesquiterpenes 16 and 17 displayed a wide spectrum of bioactivities.In the antibacterial bioassays, they showed moderate to strong activities against E. coli ATCC 10536, P. aeruginosa NTCC 6750, B. cereus ATCC 9634, B. subtilis ATCC6633, and S. aureus ATCC5141 with MIC values ranging from 10.9 to 1.2 µg/mL.Here, 16 exhibited the most potent activity against E. coli ATCC 10536 with an MIC of 1.9 µg/mL, and 17 displayed the most potent activity against P. aeruginosa NTCC 6750 with an MIC of 1.2 µg/mL.In the antifungal biotests, they exhibited weak to moderate activities against C. albicans and A. niger with MIC values ranging from 7.4 to 3.2 µg/mL.In the cytotoxic experiments, they displayed cytotoxic effects against cell lines MCF-7 and HepG2 with IC50 ranging from 6.43 to 39.23 µM.In addition, the methanolic extract of the Egyptian Red Sea L. arboreum sample yielded another tri-nor-eudesmane sesquiterpene 7oxo-tri-nor-eudesm-5-en-4β-ol (18) [37] (Figure 9).However, this nor-sesquiterpene 18 did

Tri-Nor-Eudesmane Sesquiterpenes
The methanolic extract of the Saudi Arabia Red Sea L. arboreum collection harbored two tri-nor-eudesmane sesquiterpenes teuhetenone A (16) and calamusin I (17) [36] (Figure 9).Interestingly, these two nor-sesquiterpenes 16 and 17 displayed a wide spectrum of bioactivities.In the antibacterial bioassays, they showed moderate to strong activities against E. coli ATCC 10536, P. aeruginosa NTCC 6750, B. cereus ATCC 9634, B. subtilis ATCC6633, and S. aureus ATCC5141 with MIC values ranging from 10.9 to 1.2 µg/mL.Here, 16 exhibited the most potent activity against E. coli ATCC 10536 with an MIC of 1.9 µg/mL, and 17 displayed the most potent activity against P. aeruginosa NTCC 6750 with an MIC of 1.2 µg/mL.In the antifungal biotests, they exhibited weak to moderate activities against C. albicans and A. niger with MIC values ranging from 7.4 to 3.2 µg/mL.In the cytotoxic experiments, they displayed cytotoxic effects against cell lines MCF-7 and HepG2 with IC50 ranging from 6.43 to 39.23 µM.In addition, the methanolic extract of the Egyptian Red Sea L. arboreum sample yielded another tri-nor-eudesmane sesquiterpene 7oxo-tri-nor-eudesm-5-en-4β-ol (18) [37] (Figure 9).However, this nor-sesquiterpene 18 did

Nardosinane Sesquiterpenes
Interestingly, the South China Sea soft coral L. nigrum is a rich source of nardosinane sesquiterpenes.
The chemical investigation of the Xisha collection by Yang et al. afforded two new terpenes linardosinenes B (20) and C (21) [14] (Figure 11).These two compounds were evaluated for cytotoxities against different cell lines.Sesquiterpene 20 exhibited cytotoxic effect against the THP-1 cell line with IC50 of 59.49 µM, while compound 21 displayed cytotoxicities against the cell lines SNU-398 and HT-29 with IC50 of 24.3 and 44.7 µM, respectively.In their continual study on the Xisha sample, four additional new secondary metabolites linardosinenes D-G (22-25) (Figure 11) were obtained [40].All metabolites exhibited weak inhibitory effect against bromodomain-containing protein 4 (BRD4), a promising therapeutic target in various human diseases, at a concentration of 10 µM with inhibitory rates ranging from 15.8% to 18.1%.

Nardosinane Sesquiterpenes
Interestingly, the South China Sea soft coral L. nigrum is a rich source of nardosinane sesquiterpenes.
The chemical investigation of the Xisha collection by Yang et al. afforded two new terpenes linardosinenes B (20) and C (21) [14] (Figure 11).These two compounds were evaluated for cytotoxities against different cell lines.Sesquiterpene 20 exhibited cytotoxic effect against the THP-1 cell line with IC 50 of 59.49 µM, while compound 21 displayed cytotoxicities against the cell lines SNU-398 and HT-29 with IC 50 of 24.3 and 44.7 µM, respectively.In their continual study on the Xisha sample, four additional new secondary metabolites linardosinenes D-G (22-25) (Figure 11) were obtained [40].All metabolites exhibited weak inhibitory effect against bromodomain-containing protein 4 (BRD4), a promising therapeutic target in various human diseases, at a concentration of 10 µM with inhibitory rates ranging from 15.8% to 18.1%.

Nornardosinane Sesquiterpenes
Chemical study of Xisha alcyonarian L. nigrum afforded an uncommon nornardosinane sesquiterpene linardosinene A (30) [14] (Figure 12).The absolute configuration of 30 was determined by a modified Mosher's method and TDDFT ECD approach.This isolate was evaluated for cytotoxicity against the THP-1 cell line and inhibitory activities against the PTP1B, BRD4, HDAC1, and HDAC6 protein kinases.However, it was inactive against the above-mentioned cell line and protein kinases.

Nornardosinane Sesquiterpenes
Chemical study of Xisha alcyonarian L. nigrum afforded an uncommon nornardosinane sesquiterpene linardosinene A (30) [14] (Figure 12).The absolute configuration of 30 was determined by a modified Mosher's method and TDDFT ECD approach.This isolate was evaluated for cytotoxicity against the THP-1 cell line and inhibitory activities against the PTP1B, BRD4, HDAC1, and HDAC6 protein kinases.However, it was inactive against the above-mentioned cell line and protein kinases.

Neolemnane Sesquiterpenes
A study on the chemical constituents of the Chinese soft coral L. nigrum yielded three new sesquiterpenes lineolemnenes A-C (31-33), which possessed the neolemnane carbon framework, together with the related known compound 4-acetoxy-2,8-neolemnadien-5one (34) [14] (Figure 13).It might be worth pointing out that the absolute configuration of 34 was unambiguously determined to be 1S,4S,12S by X-ray diffraction analysis for the first time.The cytotoxicities of substances 31 and 32 against SNU-398, HT-29, Capan-1, and A549 were evaluated.This revealed that 31 and 32 only exhibited cytotoxic activity against SNU-398 with IC50 values of 44.4 and 27.6 µM, respectively, and none of them showed potent inhibitory activities against the PTP1B, BRD4, HDAC1, and HDAC6 protein kinases.Compound 34 was also found in the Indonesian soft coral L. setoensis,

Neolemnane Sesquiterpenes
A study on the chemical constituents of the Chinese soft coral L. nigrum yielded three new sesquiterpenes lineolemnenes A-C (31-33), which possessed the neolemnane carbon framework, together with the related known compound 4-acetoxy-2,8-neolemnadien-5-one (34) [14] (Figure 13).It might be worth pointing out that the absolute configuration of 34 was unambiguously determined to be 1S,4S,12S by X-ray diffraction analysis for the first time.The cytotoxicities of substances 31 and 32 against SNU-398, HT-29, Capan-1, and A549 were evaluated.This revealed that 31 and 32 only exhibited cytotoxic activity against SNU-398 with IC 50 values of 44.4 and 27.6 µM, respectively, and none of them showed potent inhibitory activities against the PTP1B, BRD4, HDAC1, and HDAC6 protein kinases.Compound 34 was also found in the Indonesian soft coral L. setoensis, together with another sesquiterpene paralemnolin E (35) [16] (Figure 13).They were subjected to cytotoxic bioassays against several solid tumor and leukemia cell lines HT-29, Capan-1, A549, and SNU-398.The results revealed both two compounds had weak cytotoxic activities against the test cell lines (all IC 50 > 20 µM).Parathyrsoidin E (36) (Figure 13) was reported in the soft coral Nephthea sp., which was collected from the Egyptian coasts of the Red Sea at Sharm El-Sheikh [41].In silica study indicated this compound was a potential SARS-CoV-2 main protease inhibitor.together with another sesquiterpene paralemnolin E (35) [16] (Figure 13).They were subjected to cytotoxic bioassays against several solid tumor and leukemia cell lines HT-29, Capan-1, A549, and SNU-398.The results revealed both two compounds had weak cytotoxic activities against the test cell lines (all IC50 >20 µM).Parathyrsoidin E (36) (Figure 13) was reported in the soft coral Nephthea sp., which was collected from the Egyptian coasts of the Red Sea at Sharm El-Sheikh [41].In silica study indicated this compound was a potential SARS-CoV-2 main protease inhibitor.

Seconeolemnane Sesquiterpenes
A new sesquiterpene lineolemnene D (37) (Figure 14) was isolated and characterized from the Xisha soft coral L. nigrum [14].Structurally, this compound possessed an unusual seconeolemnane skeleton.The absolute configuration of 37 was determined to be 1S,4R,12S by TDDFT ECD approach.Bioassays including cytotoxicity against the THP-1

Seconeolemnane Sesquiterpenes
A new sesquiterpene lineolemnene D (37) (Figure 14) was isolated and characterized from the Xisha soft coral L. nigrum [14].Structurally, this compound possessed an unusual seconeolemnane skeleton.The absolute configuration of 37 was determined to be 1S,4R,12S by TDDFT ECD approach.Bioassays including cytotoxicity against the THP-1 cell line and inhibitory activities against the PTP1B, BRD4, HDAC1, and HDAC6 protein kinases were performed for this isolate.However, it was judged as inactive in these biotests.

Seconeolemnane Sesquiterpenes
A new sesquiterpene lineolemnene D (37) (Figure 14) was isolated and characterized from the Xisha soft coral L. nigrum [14].Structurally, this compound possessed an unusual seconeolemnane skeleton.The absolute configuration of 37 was determined to be 1S,4R,12S by TDDFT ECD approach.Bioassays including cytotoxicity against the THP-1 cell line and inhibitory activities against the PTP1B, BRD4, HDAC1, and HDAC6 protein kinases were performed for this isolate.However, it was judged as inactive in these biotests.

Kelsoane Sesquiterpenes
Interestingly, a new kelsoane-type sesquiterpene, namely kelsoenethiol (38) (Figure 15), was obtained from the Formosan soft coral N. erecta [30].Its structure was elucidated with the assistance of quantum chemical calculations.The cytotoxicities of 38 against A-459, P-388, and HT-29 cancer cell lines were evaluated in vitro.The results revealed compound 38 exhibited cytotoxic activities against P-388 and HT-29 cells with ED50s of 1.3 and 1.8 µg/mL, respectively.

Seconeolemnane Sesquiterpenes
A new sesquiterpene lineolemnene D (37) (Figure 14) was isolated and characterized from the Xisha soft coral L. nigrum [14].Structurally, this compound possessed an unusual seconeolemnane skeleton.The absolute configuration of 37 was determined to be 1S,4R,12S by TDDFT ECD approach.Bioassays including cytotoxicity against the THP-1 cell line and inhibitory activities against the PTP1B, BRD4, HDAC1, and HDAC6 protein kinases were performed for this isolate.However, it was judged as inactive in these biotests.

Bis-Sesquiterpenes
This group of terpenes were extremely uncommon secondary metabolites identified from the genus Litophyton with only two members (Table S1).They were described as two subgroups according to their respective monomers: bis-kelsoane dimer and eremophilanenardosinane dimer (Figure 16).All of them were the most unique type of natural products from this genus, since they were only obtained from the octocorals N. erecta and L. nigrum (Table S1).

Bis-Sesquiterpenes
This group of terpenes were extremely uncommon secondary metabolites identified from the genus Litophyton with only two members (Table S1).They were described as two subgroups according to their respective monomers: bis-kelsoane dimer and eremophilanenardosinane dimer (Figure 16).All of them were the most unique type of natural products from this genus, since they were only obtained from the octocorals N. erecta and L. nigrum (Table S1).

Bis-Kelsoane Dimers
Interestingly, a new kelsoane-type bis-sesquiterpene, namely dikelsoenyl ether (39) (Figure 17), was obtained from the Formosan soft coral N. erecta [30].Its structure was elucidated with the assistance of quantum chemical calculations.The cytotoxicties of 38 against A-459, P-388, and HT-29 cancer cell lines were evaluated in vitro.However, it was judged as inactive.

Bis-Kelsoane Dimers
Interestingly, a new kelsoane-type bis-sesquiterpene, namely dikelsoenyl ether (39) (Figure 17), was obtained from the Formosan soft coral N. erecta [30].Its structure was elucidated with the assistance of quantum chemical calculations.The cytotoxicties of 38 against A-459, P-388, and HT-29 cancer cell lines were evaluated in vitro.However, it was judged as inactive.

Bis-Kelsoane Dimers
Interestingly, a new kelsoane-type bis-sesquiterpene, namely dikelsoenyl ether (39) (Figure 17), was obtained from the Formosan soft coral N. erecta [30].Its structure was elucidated with the assistance of quantum chemical calculations.The cytotoxicties of 38 against A-459, P-388, and HT-29 cancer cell lines were evaluated in vitro.However, it was judged as inactive.

Diterpenes
Diterpenes were the largest cluster of terpenes consisting of 46 compounds.Structurally, this category of secondary metabolites could be divided into six subgroups: cembranes, eunicellanes, serrulatanes, 5,9-cyclized serrulatanes, chabrolanes, and  (Figure 17), was obtained from the Formosan soft coral N. erecta [30].Its structure was elucidated with the assistance of quantum chemical calculations.The cytotoxicties of 38 against A-459, P-388, and HT-29 cancer cell lines were evaluated in vitro.However, it was judged as inactive.

Cembrane Diterpenes
In 1975, Tursch et al. reported the isolation and structure elucidation of a new compound 2-hydroxynephtenol (41) and its known analogue nephtenol (42) (Figure 20) from the alcyonarian L. viridis, collected off Serwaru (Leti Island, Maluku Province, Indonesia) [29].Based on the chemical transformation, the absolute configuration of 42 was determined as 1R.These two terpenoids were also obtained from the Bornean octocoral Nephthea sp.[42].Biological evaluation revealed they did not exhibit repellent activity against the maize weevil Sitophilus zeamais at 250 µg/cm 2 .

Eunicellane Diterpenes
In 1987, Ochi et al. reported eunicellane diterpenes from the Litophyton animals for the first time.They were litophynins A (60) and B (61) (Figure 21) from the soft coral Litophyton sp., which was collected from a shallow area of Sukumo Bay in Kochi Prefecture, Japan [48].Their structures were fully characterized by extensive 2D NMR studies and molecular mechanics calculations.Structurally, 81 was the butyric ester derivative of 60.
In the artificial diet feeding bioassay, they exhibited insect growth inhibitory against the silkworm, Bombyx mori L., with ED50 values of 12 and 2.7 ppm, respectively.

Eunicellane Diterpenes
In 1987, Ochi et al. reported eunicellane diterpenes from the Litophyton animals for the first time.They were litophynins A (60) and B (61) (Figure 21) from the soft coral Litophyton sp., which was collected from a shallow area of Sukumo Bay in Kochi Prefecture, Japan [48].Their structures were fully characterized by extensive 2D NMR studies and molecular mechanics calculations.Structurally, 81 was the butyric ester derivative of 60.
In the artificial diet feeding bioassay, they exhibited insect growth inhibitory against the silkworm, Bombyx mori L., with ED 50 values of 12 and 2.7 ppm, respectively.
The differences among their structures were mainly at the segment C-6, C-7 and C-16, which usually formed a double bond ∆ 6 (endo), or ∆ 7 (16) (exo) accompanied with a hydroxy or a ketone at C-6.The hydroxylation or acetylation at C-12/C-13 was also observed.The absolute configuration of litophynin C (62) was determined by analysis of CD spectrum of its p-bromobenzoate, based on the exciton chirality method of allylic alcohol benzoate [49].Similarly, the absolute configuration of litophynin D (63) was determined by an application of the dibenzoate chirality rule [50].

5,9-Cyclized Serrulatane Diterpenes
Interestingly, five new diterpenes, litosetoenins A-E (80-84) (Figure 23), were iso lated from a Balinese alcyonarian L. setoensis [16].Their structures were elucidated by ex tensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance ap proach, and chemical transformations.All of them possessed a rearranged serrulatane type backbone with an unusual tricyclo[3.0.4]decane core.Moreover, 82-84 displayed in triguing tetracyclic backbones bearing either an additional tetrahydropyran or tetrahy drofuran ring, which were unprecedented and unique.All the isolates were subjected t Interestingly, these diterpenes exhibited various bioactivities.Litophynins C (62) and G (66) displayed insect growth inhibitory activity against the second instar larvae of the silkworm B. mori L. (ED 50 25 [49] and 42 [51] ppm, respectively).Litophynin D (63) exhibited significant brine shrimp lethality (LD 50 0.9 ppm) [50].Litophynins I (68) and J (69) possess significant molluscicidal and repellent activities against the muricid gastropod Drupella fragum [52].At 30 ppm concentration, diterpenes 68 and 69 exhibited 100% mortality to the snail within 24 h.They were also repellent to the gastropod when impregnated on filterpaper by 45 µg/cm 2 .These compounds, in combination with a wide variety of compounds stored in skin glands of Litophyton sp., appeared to be the foundation of a chemical defense adaptation to survive in predator-rich environments.
Litophynin C (62) (Figure 21) was also reported in the soft coral Nephthea sp., which was collected from the Egyptian coasts of the Red Sea at Sharm El-Sheikh [41].In silica study indicated this compound was a potential SARS-CoV-2 main protease inhibitor.
Miyamoto et al. investigated the chemical constituents of the mucus secreted by the soft coral Litopbyton sp., which was collected from the rocky coast of Nango-cho, Miyazaki Prefecture, Japan [53].In this study, two new eunicellin-type diterpenoids, litophynols A (70) and B (71), and three known diterpenoids litophynins E (64), H (67), and I monoacetate (72) (Figure 21) were identified.The absolute configurations of litophynols A (70) and B (71) were determined by application of the CD exciton chirality method, while the absolute configuration of litophynin E (64) was assigned by the Mosher's method.Additionally, the absolute configurations of litophynin E (64) and litophynol B (71) were further confirmed by the application of the octant rule to their ozonolysis products, respectively.Interestingly, it was found that these five eunicellin-based diterpenoids were also present in the animal bodies of Litopbyton sp. but in low yields compared with the mucus.The performed bioassays revealed these five isolates were positive in a hemolytic reaction test, and crude diterpenoid fractions exhibited ichthyotoxicity (IC 100 20 ppm).This suggests that this soft coral holds eunicellin-type diterpenoids in its mucus for the purpose of defense against predators.

5,9-Cyclized Serrulatane Diterpenes
Interestingly, five new diterpenes, litosetoenins A-E (80-84) (Figure 23), were isolated from a Balinese alcyonarian L. setoensis [16].Their structures were elucidated by extensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance approach, and chemical transformations.All of them possessed a rearranged serrulatanetype backbone with an unusual tricyclo[3.0.4]decane core.Moreover, 82-84 displayed intriguing tetracyclic backbones bearing either an additional tetrahydropyran or tetrahydrofuran ring, which were unprecedented and unique.All the isolates were subjected to the cytotoxic bioassays against cell lines HT-29, Capan-1, A549, and SNU-398.As a result, all the metabolites showed weak cytotoxic activities against these cell lines with IC50 values >20 µM.

5,9-Cyclized Serrulatane Diterpenes
Interestingly, five new diterpenes, litosetoenins A-E (80-84) (Figure 23), were isolated from a Balinese alcyonarian L. setoensis [16].Their structures were elucidated by extensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance approach, and chemical transformations.All of them possessed a rearranged serrulatane-type backbone with an unusual tricyclo[3.0.4]decane core.Moreover, 82-84 displayed intriguing tetracyclic backbones bearing either an additional tetrahydropyran or tetrahydrofuran ring, which were unprecedented and unique.All the isolates were subjected to the cytotoxic bioassays against cell lines HT-29, Capan-1, A549, and SNU-398.As a result, all the metabolites showed weak cytotoxic activities against these cell lines with IC 50 values > 20 µM.

Chabrolane Diterpenes
Cytotoxicity-guided fractionation of the ethyl acetate extract of the soft coral N. chablrolii led to the isolation of a novel diterpene, chabrolin A (85) [54] (Figure 24).This secondary metabolite possessed an unprecedented terpenoid skeleton, which was tentatively named chabrolane.Compound 85 displayed cytotoxicity against P-388, with ED 50 value of 3.18 µg/mL.However, 85 was not cytotoxic to A549 and HT-29 cell lines.Diterpene 85 was also examined for the antiviral activity against HCMV, but it was inactive.

Chabrolane Diterpenes
Cytotoxicity-guided fractionation of the ethyl acetate extract of the soft coral N. chablrolii led to the isolation of a novel diterpene, chabrolin A (85) [54] (Figure 24).This secondary metabolite possessed an unprecedented terpenoid skeleton, which was tentatively named chabrolane.Compound 85 displayed cytotoxicity against P-388, with ED50 value of 3.18 µg/mL.However, 85 was not cytotoxic to A549 and HT-29 cell lines.Diterpene 85 was also examined for the antiviral activity against HCMV, but it was inactive.

Prenylbicyclogermacrane Diterpenes
The prenylbicyclogermacrane-type diterpene, pacificin H (86) (Figure 25), was found in the soft coral Nephthea sp., which were collected from the Egyptian coasts of the Red Sea at Sharm El-Sheikh [41].In silica study indicated this compound was a potential SARS-CoV-2 main protease inhibitor.

Norditerpenes
A new norditerpene, chabrolene (87) (Figure 26), was isolated from Nephthea sp.collected from Mantanani Island, Sabah, Malaysia [42].It might be worth pointing out that natural C17 compound with a 14-membered cyclic tetraene is extremely rare.This was the

Chabrolane Diterpenes
Cytotoxicity-guided fractionation of the ethyl acetate extract of the soft coral N. chablrolii led to the isolation of a novel diterpene, chabrolin A (85) [54] (Figure 24).This secondary metabolite possessed an unprecedented terpenoid skeleton, which was tentatively named chabrolane.Compound 85 displayed cytotoxicity against P-388, with ED50 value of 3.18 µg/mL.However, 85 was not cytotoxic to A549 and HT-29 cell lines.Diterpene 85 was also examined for the antiviral activity against HCMV, but it was inactive.

Prenylbicyclogermacrane Diterpenes
The prenylbicyclogermacrane-type diterpene, pacificin H (86) (Figure 25), was found in the soft coral Nephthea sp., which were collected from the Egyptian coasts of the Red Sea at Sharm El-Sheikh [41].In silica study indicated this compound was a potential SARS-CoV-2 main protease inhibitor.

Norditerpenes
A new norditerpene, chabrolene (87) (Figure 26), was isolated from Nephthea sp.collected from Mantanani Island, Sabah, Malaysia [42].It might be worth pointing out that natural C17 compound with a 14-membered cyclic tetraene is extremely rare.This was the

Prenylbicyclogermacrane Diterpenes
The prenylbicyclogermacrane-type diterpene, pacificin H (86) (Figure 25), was found in the soft coral Nephthea sp., which were collected from the Egyptian coasts of the Red Sea at Sharm El-Sheikh [41].In silica study indicated this compound was a potential SARS-CoV-2 main protease inhibitor.

Chabrolane Diterpenes
Cytotoxicity-guided fractionation of the ethyl acetate extract of the soft coral N. chablrolii led to the isolation of a novel diterpene, chabrolin A (85) [54] (Figure 24).This secondary metabolite possessed an unprecedented terpenoid skeleton, which was tentatively named chabrolane.Compound 85 displayed cytotoxicity against P-388, with ED50 value of 3.18 µg/mL.However, 85 was not cytotoxic to A549 and HT-29 cell lines.Diterpene 85 was also examined for the antiviral activity against HCMV, but it was inactive.

Prenylbicyclogermacrane Diterpenes
The prenylbicyclogermacrane-type diterpene, pacificin H (86) (Figure 25), was found in the soft coral Nephthea sp., which were collected from the Egyptian coasts of the Red Sea at Sharm El-Sheikh [41].In silica study indicated this compound was a potential SARS-CoV-2 main protease inhibitor.

Norditerpenes
A new norditerpene, chabrolene (87) (Figure 26), was isolated from Nephthea sp.collected from Mantanani Island, Sabah, Malaysia [42].It might be worth pointing out that natural C17 compound with a 14-membered cyclic tetraene is extremely rare.This was the

Norditerpenes
A new norditerpene, chabrolene (87) (Figure 26), was isolated from Nephthea sp.collected from Mantanani Island, Sabah, Malaysia [42].It might be worth pointing out that natural C 17 compound with a 14-membered cyclic tetraene is extremely rare.This was the second report of a C 17 norditerpene with a 14-membered ring from marine organisms.Compound 87 exhibited repellent activity against the maize weevil S. zeamais at 25 µg/cm 2 .

Tetraterpenes
As revealed in literature, there was only one member of tetraterpene found in the genus Litophyton.That was all-trans-peridinin (88) (Figure 27), obtained from the Red Sea

Tetraterpenes
As revealed in literature, there was only one member of tetraterpene found in the genus Litophyton.That was all-trans-peridinin (88) (Figure 27), obtained from the Red Sea soft coral L. arboreum [43].Terpene 88 showed moderate antiproliferative activities against cell lines HUVEC and K-562 (GI 50 48.4and 53.8 µM, respectively), and moderate cytotoxicity against the HeLa cell line (IC 50 51.9µM).

Tetraterpenes
As revealed in literature, there was only one member of tetraterpene found in the genus Litophyton.That was all-trans-peridinin (88) (Figure 27), obtained from the Red Sea soft coral L. arboreum [43].Terpene 88 showed moderate antiproliferative activities against cell lines HUVEC and K-562 (GI50 48.4 and 53.8 µM, respectively), and moderate cytotoxicity against the HeLa cell line (IC50 51.9 µM).

4α-Methylated Steroids
Examination of less polar fractions of the extract of the Indonesian soft coral L. viridis, which was collected in the Lesser Sunda Islands, led to the isolation of a novel polyoxygenated sterol 4α-methyl-3β,8β-dihydroxy-5α-ergost-24(28)-en-23-one (94) [56] (Figure 29).The structure and relative configuration of 94 were established unambiguously by X-ray diffraction analysis on its p-bromobenzoate derivative.This steroid was also obtained from Bornean octocoral Nephthea sp.[42].Biological evaluation revealed compound 94 did not exhibit repellent activity against the maize weevil S. zeamais at 250 µg/cm 2 .

Končić et al. conducted the first chemical investigation on the metabolic profile of
the Red Sea alcyonarian L. mollis, resulting in the isolation of ten 4α-methylated steroids 95-104 [57] (Figure 29).These steroids differed not only in the substitution of hydroxyl groups at the steroidal nucleus but also in diverse oxidation of side chains.The absolute configuration of C-24 in compounds 96, 99, and 103 was assigned as R based on the chemical shift difference between C-26 and C-27 carbon atoms, which was a powerful rule to determine the absolute configuration of steroidal side chains [58][59][60].The cytotoxic activities of metabolites 95-103 were evaluated against cell lines K562 and A549 [57].As a result, compounds 95 and 99-102 displayed potent cytotoxicity against K562 cells with IC 50 values ranging from 5.6 to 8.9 µM.Meanwhile, these compounds showed low toxicity against healthy PBMCs, thus denoting interesting differential toxicity.Additionally, the tested steroids exhibited moderate levels of toxicity against A549 cells with IC 50 values around 20 µM, further underlining their antileukemic activity.
The Red Sea soft coral L. arboreum was frequently encountered by marine natural product chemists.Shaker et al. found that the Egyptian specimen L. arboreum harbored 4α,24-dimethyl-cholest-22Z-en-3β-ol (106) (Figure 29), the complete assignments of 13 C NMR data of which was reported for the first time [62].Interestingly, the presence of nebrosteroid M (98) in another Egyptian sample of L. arboreum had been reported by Mahmoud et al., which was collected in front of the National Institute of Oceanography and Fisheries at Hurghada province [37].It was also found that sterol 98 showed cytotoxic effect against A549 cell line (IC 50 36.9µmol/mL).Moreover, this compound exhibited moderate cytotoxicity against MCF-7 (IC 50 55.3 µmol/mL), but no activity against HepG2 (IC 50 > 100 µmol/mL).
Ahmed et al. also made an Egyptian collection of L. arboreum from Neweba.Chemical investigation of this sample led to isolation of previously reported 4α-methylated steroids 98, 99, and 103 [33] (Figure 29).Anti-malarial activities against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of P. falciparum, together with the cytotoxic effect against the Vero cell line, were evaluated for these three isolates.However, they were judged as inactive at the concentration of 4.76 mg/mL in the above-mentioned bioassays.
Co-existence of three known secondary metabolites 109, 111, and 114 in the Egyptian Red Sea collection L. arboretum from Hurghada was reported by Shaker et al. [62].Recently, a study on another Egyptian Red Sea alcyonarian L. arboreum collected at the same coast by Mahmoud et al. disclosed the existence of sterol 114, too [37].In this study, metabolite 114 exhibited noticeable cytotoxicity against A549 cell line (IC 50 28.5 µmol/mL) and weak cytotoxic activities against both cell lines MCF-7 and HepG2 (IC 50 70.0and 77.6 µmol/mL, respectively).
A novel seco-steroid 13,14-seco-22-norergosta-4,24(28)-dien-19-hydroperoxide-3-one (117) (Figure 30) together with the known one 110 were found in the chemical investigation of Saudi Arabian Red Sea specimen L. arboreum by Ghandourah et al., which was collected from the North of Jeddah coast [39].They showed antiproliferative effects toward three different cancer cell lines, MCF-7, HCT116, and HepG-2.(It might be worth pointing out no specific data were provided in this article.)In addition, Hawas et al. reported the presence of sterols 109 and 114 in another Saudi Arabian Red Sea sample L. arboreum [20].
It might be worth pointing out that the Formosan soft corals of the title genus were abundant sources of ergostane-type and related degraded steroids.
In order to search for novel bioactive substances from Formosan soft coral N. chabrolii, two new 19-oxygenated steroids, nebrosteroids O and P (120 and 121) (Figure 30), were isolated [67].Their cytotoxicities against A549, HT-29, and P-388 cell lines were evaluated, and the results showed they exhibited different levels cytotoxic activities with ED 50 values ranging from 1.2 to 9.5 µg/mL.They were also examined for their antiviral activity towards human cytomegalovirus (HCMV) using a human embryonic lung (HEL) cell line.However, all of them were found to be inactive (ED 50 > 100 µg/mL).Further chemical profiling of this specimen led to a new 19-oxygenated steroid, nebrosteroid Q (95) and two new cytotoxic 19-norergosterols, nebrosteroids R and S (123 and 124) [68] (Figure 30).Interestingly, these three sterols also displayed cytotoxic activities against A549, HT-29, and P-388 cell lines, but none of them was found to have anti-HCMV activity.
A new 10-demethylated steroid, nephtheasteroid A (129), a new 19-oxygenated steroid, nephtheasteroid B (130), as well as five known steroids 114 and 131-134 (Figure 30) were isolated from the organic extract of a Formosan soft coral N. erecta [73].The cytotoxicity of these isolates against the proliferation of a limited panel of cancer cell lines, including K562, Molt-4, Sup-T1, and U937, was evaluated.As a result, compounds 131-133 exhibited cytotoxicity against all or part of the above cell lines with IC 50 values ranging from 6.5 to 19.9 µM.Further study indicated sterol 133 inhibited human small cell lung cancer growth via apoptosis induction [74].
cytotoxicities against A549 and Hepg2 cell lines.Further study on this species yielded six more cholesta-1,4-dien-3-one derivatives; 139-144 were found [76] (Figure 31).The absolute configuration at C-22 of 139 was determined to be R by Mosher's method.All isolated compounds exhibited cytotoxic activity against HeLa cells with IC50 values ranging from 7.51 to 18.72 µg/mL.Interestingly, the existence of a novel unusual pentacyclic hemiacetal sterol nephthoacetal (145) (Figure 31) in the soft coral Nephthea sp. was disclosed [77].Compound 145 not only strongly inhibited the settlement of Bugula neritina larvae with an EC50 value of 2.5 µg/mL, but also exhibited low toxicity towards this species of larvae with LC50 > 25.0 µg/mL.Moreover, this sterol showed moderate cytotoxicity against HeLa cells with an EC50 value of 12.3 µg/mL.Recently, dendronesterone C (146) (Figure 31) was obtained from the soft coral Nephthea sp., which were collected from the Egyptian coasts of the Red Sea at Sharm El-Sheikh [41].In silica study indicated this compound was a potential SARS-CoV-2 main protease inhibitor.

Nitrogen-Containing Metabolites
Nitrogen-containing metabolites were a small cluster of secondary metabolites from the genus Litophyton.This cluster consisted of 11 compounds, which could be divided into three subgroups: ceramides, pyrimidines, and peptides.These secondary metabolites

Nitrogen-Containing Metabolites
Nitrogen-containing metabolites were a small cluster of secondary metabolites from the genus Litophyton.This cluster consisted of 11 compounds, which could be divided into three subgroups: ceramides, pyrimidines, and peptides.These secondary metabolites were isolated from the species L. arboretum and Nephthea sp., which live in different regions of Red Sea and South China Sea (Table S1).

Nitrogen-Containing Metabolites
Nitrogen-containing metabolites were a small cluster of secondary metabolites from the genus Litophyton.This cluster consisted of 11 compounds, which could be divided into three subgroups: ceramides, pyrimidines, and peptides.These secondary metabolites were isolated from the species L. arboretum and Nephthea sp., which live in different regions of Red Sea and South China Sea (Table S1).

Pyrimidines
Study on the chemical constituents of Saudi Arabian soft coral L. arboreum led to the isolation and identification of thymine (155) and thymidine (156) [36] (Figure 34).Investigation on the compositions of Egyptian collection L. arboreum revealed the co-isolation of thymine (155), uracil (157), and uridine (158) [79] (Figure 34).Metabolites 155, 157, and 158 were in vitro estimated for their cytotoxic activities against three human cancer cell lines, A549, MCF-7, and HepG2, and antileishmanial potential against Leishmania major.However, none of them was active in these bioassays.

Pyrimidines
Study on the chemical constituents of Saudi Arabian soft coral L. arboreum led to the isolation and identification of thymine (155) and thymidine (156) [36] (Figure 34).Investigation on the compositions of Egyptian collection L. arboreum revealed the co-isolation of thymine (155), uracil (157), and uridine (158) [79] (Figure 34).Metabolites 155, 157, and 158 were in vitro estimated for their cytotoxic activities against three human cancer cell lines, A549, MCF-7, and HepG2, and antileishmanial potential against Leishmania major.However, none of them was active in these bioassays.

Lipids
This cluster consisted of one prostaglandin, four γ-lactones, four fatty acids, and two glycerol ethers.These secondary metabolites distributed in L. arboretum and unclearly identified Litophyton sp. which were collected in the Red Sea and the waters around Japan (Table S1).

Prostaglandins
The sole prostaglandin from the genus Litophyton, PGB2 methyl ester (164) (Figure 36), was characterized in the research of Red Sea alcyonarian L. arboreum, which lived in the gulf of Aqaba, Eilat, Israel [81].

Lipids
This cluster consisted of one prostaglandin, four γ-lactones, four fatty acids, and two glycerol ethers.These secondary metabolites distributed in L. arboretum and unclearly identified Litophyton sp. which were collected in the Red Sea and the waters around Japan (Table S1).

Prostaglandins
The sole prostaglandin from the genus Litophyton, PGB 2 methyl ester (164) (Figure 36), was characterized in the research of Red Sea alcyonarian L. arboreum, which lived in the gulf of Aqaba, Eilat, Israel [81].

γ-Lactones
Two new branched-chain lipids containing a γ-lactone ring, which was named litophytolides A (165) and B (166) (Figure 37), were isolated from a Japanese soft coral Litophyton sp.[82].The difference in their structures was the replacement of the butyryl group in 165 by the acetyl group in 166.
Chemical study of Israeli Red Sea alcyonarian L. arboreum led to the discovery of two novel γ-lactones with unsaturated chains 167 and 168 [81] (Figure 37).The absolute configuration of C-5 was assigned as S for 167 and 168 by applying the Mosher's method.In the toxicity bioassay, these two secondary metabolites were toxic to brine shrimp Artemia salina (CC50 15.3 and 21.4 µg/mL, respectively).Antibacterial evaluations indicated the two γ-lactones were active only against Gram-positive bacteria S. aureus and B. subtilis with diameters of inhibition zones ranging from 5.6 to 18.6 mm, but they were inactive against Gram-negative bacterium E. coli and yeast Saccharomyces cerevisiae.

γ-Lactones
Two new branched-chain lipids containing a γ-lactone ring, which was named litophytolides A (165) and B (166) (Figure 37), were isolated from a Japanese soft coral Litophyton sp.[82].The difference in their structures was the replacement of the butyryl group in 165 by the acetyl group in 166.

γ-Lactones
Two new branched-chain lipids containing a γ-lactone ring, which was named litophytolides A (165) and B (166) (Figure 37), were isolated from a Japanese soft coral Litophyton sp.[82].The difference in their structures was the replacement of the butyryl group in 165 by the acetyl group in 166.
Chemical study of Israeli Red Sea alcyonarian L. arboreum led to the discovery of two novel γ-lactones with unsaturated chains 167 and 168 [81] (Figure 37).The absolute configuration of C-5 was assigned as S for 167 and 168 by applying the Mosher's method.In the toxicity bioassay, these two secondary metabolites were toxic to brine shrimp Artemia salina (CC50 15.3 and 21.4 µg/mL, respectively).Antibacterial evaluations indicated the two γ-lactones were active only against Gram-positive bacteria S. aureus and B. subtilis with diameters of inhibition zones ranging from 5.6 to 18.6 mm, but they were inactive against Gram-negative bacterium E. coli and yeast Saccharomyces cerevisiae.

Fatty Acids
During a search for the chemical constituents of a Japanese soft coral Litophyton sp., methyl (5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-icosapentaenoate (169) was encountered, together with the above-described γ-lactones litophytolides A (165) and B (166) [82] (Figure 38).The co-occurrence of litophytolides 165 and 166 and unsaturated fatty acid 169 in the same animal led to the proposed biogenesis of branched-chain lipids with a γ-lactone ring that involved the condensation of unsaturated fatty acids with pyruvate.GC-MS analysis of the fraction of a Israeli alcyonarian L. arboreum revealed the presence of arachidonic Chemical study of Israeli Red Sea alcyonarian L. arboreum led to the discovery of two novel γ-lactones with unsaturated chains 167 and 168 [81] (Figure 37).The absolute configuration of C-5 was assigned as S for 167 and 168 by applying the Mosher's method.In the toxicity bioassay, these two secondary metabolites were toxic to brine shrimp Artemia salina (CC 50 15.3 and 21.4 µg/mL, respectively).Antibacterial evaluations indicated the two γ-lactones were active only against Gram-positive bacteria S. aureus and B. subtilis with diameters of inhibition zones ranging from 5.6 to 18.6 mm, but they were inactive against Gram-negative bacterium E. coli and yeast Saccharomyces cerevisiae.

Glycerol Ethers
Investigation of the chemical compositions of Red Sea soft coral L. arboreum, which inhabited the coast of Sharm El-Sheikh, Egypt, resulted in the isolation and characterization of chimyl alcohol (173) [34] (Figure 39).This alcohol not only showed cytotoxic effects against the cell lines HeLa and Vero (IC 50 23.35and 60 µM, respectively), but also exhibited inhibitory activity against HIV-1 protease (IC 50 26.6 µM).The presence of 173 in the Saudi Arabian Red Sea sample L. arboreum was reported [36].

Glycerol Ethers
Investigation of the chemical compositions of Red Sea soft coral L. arboreum, which inhabited the coast of Sharm El-Sheikh, Egypt, resulted in the isolation and characterization of chimyl alcohol (173) [34] (Figure 39).This alcohol not only showed cytotoxic effects against the cell lines HeLa and Vero (IC50 23.35 and 60 µM, respectively), but also exhibited inhibitory activity against HIV-1 protease (IC50 26.6 µM).The presence of 173 in the Saudi Arabian Red Sea sample L. arboreum was reported [36].
Chemical study of Red Sea specimen L. arboreum, which was collected at Hurghada, Egypt, disclosed the co-existence of chimyl alcohol (173) and batyl alcohol (174) [37] (Figure 39).Cytotoxicity bioassays were also performed for these two glycerol ethers, but none of them was active against the tested cell lines A549, MCF-7, and HepG2 (all IC50 > 100 µmol/mL).

Other Metabolites
Interestingly, diphenyl selenide (175) (Figure 40) was identified as a secondary metabolite of a soft coral Nephthea sp., which resided in South China Sea [80].

Discussion
The current work presents an up-to-date documentation of the reported studies on the genus Litophyton with a special focus on their diverse chemical classes of secondary metabolites and their bioactivities.The investigated soft corals of this genus inhabited various marine environments from tropical to temperate regions, especially in the South China Sea, Red Sea, and the waters around Taiwan, Indonesia, Malaysia, and Japan (Figure 41, Table S1).
A total of 175 compounds from a variety of species of this genus were reported from 1975 to July 2023, covering a period of almost five decades.These substances illustrated Chemical study of Red Sea specimen L. arboreum, which was collected at Hurghada, Egypt, disclosed the co-existence of chimyl alcohol (173) and batyl alcohol (174) [37] (Figure 39).Cytotoxicity bioassays were also performed for these two glycerol ethers, but none of them was active against the tested cell lines A549, MCF-7, and HepG2 (all IC 50 > 100 µmol/mL).

Other Metabolites
Interestingly, diphenyl selenide (175) (Figure 40) was identified as a secondary metabolite of a soft coral Nephthea sp., which resided in South China Sea [80].

Glycerol Ethers
Investigation of the chemical compositions of Red Sea soft coral L. arboreum, which inhabited the coast of Sharm El-Sheikh, Egypt, resulted in the isolation and characterization of chimyl alcohol (173) [34] (Figure 39).This alcohol not only showed cytotoxic effects against the cell lines HeLa and Vero (IC50 23.35 and 60 µM, respectively), but also exhibited inhibitory activity against HIV-1 protease (IC50 26.6 µM).The presence of 173 in the Saudi Arabian Red Sea sample L. arboreum was reported [36].
Chemical study of Red Sea specimen L. arboreum, which was collected at Hurghada, Egypt, disclosed the co-existence of chimyl alcohol (173) and batyl alcohol (174) [37] (Figure 39).Cytotoxicity bioassays were also performed for these two glycerol ethers, but none of them was active against the tested cell lines A549, MCF-7, and HepG2 (all IC50 > 100 µmol/mL).

Other Metabolites
Interestingly, diphenyl selenide (175) (Figure 40) was identified as a secondary metabolite of a soft coral Nephthea sp., which resided in South China Sea [80].

Discussion
The current work presents an up-to-date documentation of the reported studies on the genus Litophyton with a special focus on their diverse chemical classes of secondary metabolites and their bioactivities.The investigated soft corals of this genus inhabited var-

Conclusions
As presented in this work, the soft corals of the genus Litophyton harbor an array of structurally unique and diversely bioactive secondary metabolites, including sesquiterpenes, sesquiterpene dimers, diterpenes, norditerpenes, tetraterpenes, meroterpenes, steroids, ceramides, pyrimidines, peptides, prostaglandins, γ-lactones, fatty acids, glycerol ethers, and selenides (Figure 42, Table S1).However, only nine species including L. arboreum, L. nigrum, L. setoensis, L. viridis, L. viscudium, L. mollis, N. erecta, N. columnaris, and N. chablrolii have been investigated besides unclearly identified Litophyton sp. and Nephthea sp.(Figure 43, Table S1), which were a very small proportion of the whole genus Litophyton [10].It is clear that there is a need for increased research on exploration of more species of this genus, which are hidden treasure troves of novel marine natural products.
As shown in this work, the eunicellane and cembrene diterpenes displayed a broad range of bioactivities including antifungal, anti-HIV, antitumor, anti-inflammatory, antibacterial, insect growth inhibitory, and molluscicidal properties (Table S1).However, due to the limited amounts of these metabolites in soft corals, exploration of new technologies to gain efficient substances is becoming impendingly demanded.Very recently, terpene cyclase genes that produce eunicellane and cembrene diterpenes have been found in soft corals such as Erythropodium caribaeorum and Dendronephtha gigantean [83,84].Investigating the biogenesis of the secondary metabolites of the genus Litophyton and the utilization of biosyntheses in rapid production of terpenes would be another significant and hot research topic in this field.Moreover, the discovery of novel terpene biosynthetic gene clusters could provide potential bioengineering applications for industry.

Figure 1 .
Figure 1.Carbon frameworks of the sesquiterpenes reported from soft corals of the genus Litophyton.

Figure 2 .
Figure 2. Chemical structure of the bicyclogermacrane sesquiterpene isolated from soft corals of the genus Litophyton.

Figure 3 .
Figure 3.Chemical structure of the sec-germacrane sesquiterpene from soft corals of the genus Litophyton.

Figure 1 .
Figure 1.Carbon frameworks of the sesquiterpenes reported from soft corals of the genus Litophyton.

Figure 1 .
Figure 1.Carbon frameworks of the sesquiterpenes reported from soft corals of the genus Litophyton.

Figure 2 .
Figure 2. Chemical structure of the bicyclogermacrane sesquiterpene isolated from soft corals of the genus Litophyton.

Figure 3 .
Figure 3.Chemical structure of the sec-germacrane sesquiterpene from soft corals of the genus Litophyton.

Figure 2 .
Figure 2. Chemical structure of the bicyclogermacrane sesquiterpene isolated from soft corals of the genus Litophyton.

Figure 1 .
Figure 1.Carbon frameworks of the sesquiterpenes reported from soft corals of the genus Litophyton.

Figure 2 .
Figure 2. Chemical structure of the bicyclogermacrane sesquiterpene isolated from soft corals of the genus Litophyton.

Figure 3 .
Figure 3.Chemical structure of the sec-germacrane sesquiterpene from soft corals of the genus Litophyton.

Figure 3 .
Figure 3.Chemical structure of the sec-germacrane sesquiterpene from soft corals of the genus Litophyton.

35 Figure 4 .
Figure 4.Chemical structures of the guaiane sesquiterpenes from soft corals of the genus Litophyton.

Figure 4 .
Figure 4.Chemical structures of the guaiane sesquiterpenes from soft corals of the genus Litophyton.

Figure 4 .
Figure 4.Chemical structures of the guaiane sesquiterpenes from soft corals of the genus Litophyton.

Figure 5 .
Figure 5.Chemical structures of the pseudoguaiane sesquiterpenes from soft corals of the genus Litophyton.

Figure 5 .
Figure 5.Chemical structures of the pseudoguaiane sesquiterpenes from soft corals of the genus Litophyton.

Figure 6 .
Figure 6.Chemical structure of the himachalene sesquiterpene from soft corals of the genus Litophyton.

Figure 6 .
Figure 6.Chemical structure of the himachalene sesquiterpene from soft corals of the genus Litophyton.

Figure 6 .
Figure 6.Chemical structure of the himachalene sesquiterpene from soft corals of the genus Litophyton.

Figure 7 .
Figure 7.Chemical structure of the eudesmane sesquiterpene from soft corals of the genus Litophyton.

Figure 8 .
Figure 8.Chemical structure of the seco-eudesmane sesquiterpene from soft corals of the genus Litophyton.

Figure 7 .
Figure 7.Chemical structure of the eudesmane sesquiterpene from soft corals of the genus Litophyton.

Figure 6 .
Figure 6.Chemical structure of the himachalene sesquiterpene from soft corals of the genus Litophyton.

Figure 7 .
Figure 7.Chemical structure of the eudesmane sesquiterpene from soft corals of the genus Litophyton.

Figure 8 .
Figure 8.Chemical structure of the seco-eudesmane sesquiterpene from soft corals of the genus Litophyton.

Figure 8 .
Figure 8.Chemical structure of the seco-eudesmane sesquiterpene from soft corals of the genus Litophyton.

Figure 9 .
Figure 9.Chemical structures of the tri-nor-eudesmane sesquiterpenes from soft corals of the genus Litophyton.

Figure 9 .
Figure 9.Chemical structures of the tri-nor-eudesmane sesquiterpenes from soft corals of the genus Litophyton.

Figure 9 .
Figure 9.Chemical structures of the tri-nor-eudesmane sesquiterpenes from soft corals of the genus Litophyton.

Figure 10 .
Figure 10.Chemical structure of the eremophilane sesquiterpene from soft corals of the genus Litophyton.

Figure 10 .
Figure 10.Chemical structure of the eremophilane sesquiterpene from soft corals of the genus Litophyton.

Figure 11 .
Figure 11.Chemical structures of the nardosinane sesquiterpenes from soft corals of the genus Litophyton.

Figure 11 .
Figure 11.Chemical structures of the nardosinane sesquiterpenes from soft corals of the genus Litophyton.

Figure 12 .
Figure 12.Chemical structure of the nornardosinane sesquiterpene from soft corals of the genus Litophyton.

Figure 12 .
Figure 12.Chemical structure of the nornardosinane sesquiterpene from soft corals of the genus Litophyton.

Figure 13 .
Figure 13.Chemical structures of the neolemnane sesquiterpenes from soft corals of the genus Litophyton.

Figure 13 .
Figure 13.Chemical structures of the neolemnane sesquiterpenes from soft corals of the genus Litophyton.

Figure 13 .
Figure 13.Chemical structures of the neolemnane sesquiterpenes from soft corals of the genus Litophyton.

Figure 14 .
Figure 14.Chemical structure of the seconeolemnane sesquiterpene from soft corals of the genus Litophyton.

Figure 15 .
Figure 15.Chemical structure of the kelsoane sesquiterpene from soft corals of the genus Litophyton.

Figure 14 .
Figure 14.Chemical structure of the seconeolemnane sesquiterpene from soft corals of the genus Litophyton.

Figure 13 .
Figure 13.Chemical structures of the neolemnane sesquiterpenes from soft corals of the genus Litophyton.

Figure 14 .
Figure 14.Chemical structure of the seconeolemnane sesquiterpene from soft corals of the genus Litophyton.

Figure 15 .
Figure 15.Chemical structure of the kelsoane sesquiterpene from soft corals of the genus Litophyton.

Figure 15 .
Figure 15.Chemical structure of the kelsoane sesquiterpene from soft corals of the genus Litophyton.

Figure 16 .
Figure 16.Carbon frameworks of the bis-sesquiterpenes from soft corals of the genus Litophyton.

Figure 16 .
Figure 16.Carbon frameworks of the bis-sesquiterpenes from soft corals of the genus Litophyton.

Figure 17 .
Figure 17.Chemical structure of the kelsoane-type bis-sesquiterpene from soft corals of the genus Litophyton.

Figure 18 .
Figure 18.Chemical structure of the eremophilane-nardosinane bis-sesquiterpene from soft corals of the genus Litophyton.

Figure 17 .
Figure 17.Chemical structure of the kelsoane-type bis-sesquiterpene from soft corals of the genus Litophyton.

Figure 17 .
Figure 17.Chemical structure of the kelsoane-type bis-sesquiterpene from soft corals of the genus Litophyton.

Figure 18 .
Figure 18.Chemical structure of the eremophilane-nardosinane bis-sesquiterpene from soft corals of the genus Litophyton.

Figure 18 .
Figure 18.Chemical structure of the eremophilane-nardosinane bis-sesquiterpene from soft corals of the genus Litophyton.

Figure 19 .
Figure 19.Carbon frameworks of the diterpenes reported from soft corals of the genus Litophyton.

Figure 19 .
Figure 19.Carbon frameworks of the diterpenes reported from soft corals of the genus Litophyton.5.1.Cembrane Diterpenes In 1975, Tursch et al. reported the isolation and structure elucidation of a new compound 2-hydroxynephtenol (41) and its known analogue nephtenol (42) (Figure20) from the alcyonarian L. viridis, collected off Serwaru (Leti Island, Maluku Province, Indonesia)[29].Based on the chemical transformation, the absolute configuration of 42 was determined as

35 Figure 20 .
Figure 20.Chemical structures of the cembrane diterpenes from soft corals of the genus Litophyton.

Figure 20 .
Figure 20.Chemical structures of the cembrane diterpenes from soft corals of the genus Litophyton.

3 Figure 21 .
Figure 21.Chemical structures of the eunicellane diterpenes from soft corals of the genus Litophyton.

Figure 22 .
Figure 22.Chemical structures of the serrulatane diterpenes from soft corals of the genus Litophyton.

Figure 21 .
Figure 21.Chemical structures of the eunicellane diterpenes from soft corals of the genus Litophyton.

Figure 21 .
Figure 21.Chemical structures of the eunicellane diterpenes from soft corals of the genus Litophyton.

Figure 22 .
Figure 22.Chemical structures of the serrulatane diterpenes from soft corals of the genus Litophyton.

Figure 22 .
Figure 22.Chemical structures of the serrulatane diterpenes from soft corals of the genus Litophyton.

Figure 24 .
Figure 24.Chemical structure of the chabrolane diterpene from soft corals of the genus Litophyton.

Figure 25 .
Figure 25.Chemical structure of the prenylbicyclogermacrane diterpene from soft corals of the genus Litophyton.

Figure 24 .
Figure 24.Chemical structure of the chabrolane diterpene from soft corals of the genus Litophyton.

Figure 25 .
Figure 25.Chemical structure of the prenylbicyclogermacrane diterpene from soft corals of the genus Litophyton.

Figure 24 .
Figure 24.Chemical structure of the chabrolane diterpene from soft corals of the genus Litophyton.

Figure 24 .
Figure 24.Chemical structure of the chabrolane diterpene from soft corals of the genus Litophyton.

Figure 25 .
Figure 25.Chemical structure of the prenylbicyclogermacrane diterpene from soft corals of the genus Litophyton.

Figure 25 .
Figure 25.Chemical structure of the prenylbicyclogermacrane diterpene from soft corals of the genus Litophyton.

Figure 26 .
Figure 26.Chemical structure of the norditerpene from soft corals of the genus Litophyton.

Figure 26 .
Figure 26.Chemical structure of the norditerpene from soft corals of the genus Litophyton.

Figure 26 .
Figure 26.Chemical structure of the norditerpene from soft corals of the genus Litophyton.

Figure 27 .
Figure 27.Chemical structure of the tetraterpene from soft corals of the genus Litophyton.

Figure 27 .
Figure 27.Chemical structure of the tetraterpene from soft corals of the genus Litophyton.

35 Figure 28 .
Figure 28.Chemical structures of the meroterpenes from soft corals of the genus Litophyton.

Figure 28 .
Figure 28.Chemical structures of the meroterpenes from soft corals of the genus Litophyton.

35 Figure 29 .
Figure 29.Chemical structures of the 4α-methylated steroids from soft corals of the genus Litophyton.

Figure 29 .
Figure 29.Chemical structures of the 4α-methylated steroids from soft corals of the genus Litophyton.

Figure 30 .
Figure 30.Chemical structures of the ergostane-type and related steroids from soft corals of the genus Litophyton.

Figure 30 .
Figure 30.Chemical structures of the ergostane-type and related steroids from soft corals of the genus Litophyton.

Figure 32 .
Figure 32.Chemical structures of the pregnane-type and related steroids from soft corals of the genus Litophyton.

Figure 32 .
Figure 32.Chemical structures of the pregnane-type and related steroids from soft corals of the genus Litophyton.

Figure 32 .
Figure 32.Chemical structures of the pregnane-type and related steroids from soft corals of the genus Litophyton.

Figure 33 .
Figure 33.Chemical structures of the ceramides from soft corals of the genus Litophyton.Figure 33.Chemical structures of the ceramides from soft corals of the genus Litophyton.

Figure 33 .
Figure 33.Chemical structures of the ceramides from soft corals of the genus Litophyton.Figure 33.Chemical structures of the ceramides from soft corals of the genus Litophyton.

Figure 34 .
Figure 34.Chemical structures of the pyrimidines from soft corals of the genus Litophyton.

Figure 34 .
Figure 34.Chemical structures of the pyrimidines from soft corals of the genus Litophyton.

Figure 34 .
Figure 34.Chemical structures of the pyrimidines from soft corals of the genus Litophyton.

Figure 35 .
Figure 35.Chemical structures of the peptides from soft corals of the genus Litophyton.

Figure 35 .
Figure 35.Chemical structures of the peptides from soft corals of the genus Litophyton.

35 Figure 36 .
Figure 36.Chemical structure of the prostaglandin from soft corals of the genus Litophyton.

Figure 37 .
Figure 37.Chemical structures of the γ-lactones from soft corals of the genus Litophyton.

Figure 36 .
Figure 36.Chemical structure of the prostaglandin from soft corals of the genus Litophyton.

35 Figure 36 .
Figure 36.Chemical structure of the prostaglandin from soft corals of the genus Litophyton.

Figure 37 .
Figure 37.Chemical structures of the γ-lactones from soft corals of the genus Litophyton.

Figure 37 .
Figure 37.Chemical structures of the γ-lactones from soft corals of the genus Litophyton.

Figure 37 .
Figure 37.Chemical structures of the γ-lactones from soft corals of the genus Litophyton.

Figure 38 .
Figure 38.Chemical structures of the fatty acids from soft corals of the genus Litophyton.Figure 38.Chemical structures of the fatty acids from soft corals of the genus Litophyton.

Figure 38 .
Figure 38.Chemical structures of the fatty acids from soft corals of the genus Litophyton.Figure 38.Chemical structures of the fatty acids from soft corals of the genus Litophyton.

Figure 39 .
Figure 39.Chemical structures of the glycerol ethers from soft corals of the genus Litophyton.

Figure 40 .
Figure 40.Chemical structure of the selenide from soft corals of the genus Litophyton.

Figure 39 .
Figure 39.Chemical structures of the glycerol ethers from soft corals of the genus Litophyton.

Figure 39 .
Figure 39.Chemical structures of the glycerol ethers from soft corals of the genus Litophyton.

Figure 40 .
Figure 40.Chemical structure of the selenide from soft corals of the genus Litophyton.

Figure 40 .
Figure 40.Chemical structure of the selenide from soft corals of the genus Litophyton.
Mar. Drugs 2023, 21, 523 29 of 35uncommon marine natural products, some of which were only identified in the genus Litophyton.

Figure 41 .
Figure 41.The distribution of the investigated species of the genus Litophyton.

Figure 42 .
Figure 42.Chemical profile of secondary metabolites from soft corals of the genus Litophyton.

Figure 41 .
Figure 41.The distribution of the investigated species of the genus Litophyton.

Figure 41 .
Figure 41.The distribution of the investigated species of the genus Litophyton.

Figure 42 .
Figure 42.Chemical profile of secondary metabolites from soft corals of the genus Litophyton.

Figure 42 .
Figure 42.Chemical profile of secondary metabolites from soft corals of the genus Litophyton.

Figure 43 .
Figure 43.Number of compounds reported from different species of the genus Litophyton.

Figure 43 .
Figure 43.Number of compounds reported from different species of the genus Litophyton.