Diversified Chemical Structures and Bioactivities of the Chemical Constituents Found in the Brown Algae Family Sargassaceae

Sargassaceae, the most abundant family in Fucales, was recently formed through the merging of the two former families Sargassaceae and Cystoseiraceae. It is widely distributed in the world’s oceans, notably in tropical coastal regions, with the exception of the coasts of Antarctica and South America. Numerous bioactivities have been discovered through investigations of the chemical diversity of the Sargassaceae family. The secondary metabolites with unique structures found in this family have been classified as terpenoids, phlorotannins, and steroids, among others. These compounds have exhibited potent pharmacological activities. This review describes the new discovered compounds from Sargassaceae species and their associated bioactivities, citing 136 references covering from March 1975 to August 2023.

Since 1973, studies on Sargassaceae species have experienced rapid growth, leading to the discovery of a multitude of novel compounds with potent bioactivities.Valls and Piovetti summarized 134 new diterpenoids isolated from the former Cystoseiraceae family between 1973 and January 1995 [20], and de Sousa et al. [18] and Gouveira et al. [21] compiled the secondary metabolites isolated from various Cystoseira species from 1995 Piovetti summarized 134 new diterpenoids isolated from the former Cystoseiraceae family between 1973 and January 1995 [20], and de Sousa et al. [18] and Gouveira et al. [21] compiled the secondary metabolites isolated from various Cystoseira species from 1995 to 2016.Chen and Liu [22] and Rushdi et al. [23] reviewed the chemical constituents of Sargassum species and their biological activities from 1974 to 2020.Rushdi et al. [24] also provided an overview of secondary metabolites isolated from Turbinaria species between 1972 and 2019.Muñoz et al. [4] summarized the linear diterpenes from Bifurcaria bifurcata, emphasizing biosynthetic pathways, biological activities, chemotaxonomy, and ecology.This review attempts to summarize the literature data on the new compounds from the Sargassaceae family and their biological activities.

Chemistry and Biological Activities of the Compounds from the Sargassaceae family
Sargassaceae is a family of marine macroalgae comprising over 20 genera and more than 1000 species, and some species are shown in Figure 1.While many genera of this family show a limited distribution, the genera Bifurcaria, Cystophora, and Halidrys display a disjunct distribution [14].When examining the chemical constituents from Sargassacean species, numerous new structures were obtained, which mainly include terpenoids (encompassing meroterpenoids), phloroglucinol derivatives, steroids, and other types.

Terpenoids
Terpenoids, a class of predominantly secondary metabolites, have been discovered in the Sargassaceae family [25,26].Specifically, 223 novel terpenoids have been obtained from five different Sargassacean genera, namely Cystoseira, Sargassum, Cystophora, Bifurcaria, and Turbinaria.Based on the number of isoprene units and the biosynthesis pathway these isolated compounds can be categorized into monoterpenoids, sesquiterpenoids diterpenoids, triterpenes, and meroterpenes.

Norditerpenoids
Sixteen new norditerpenoid compounds (Figure 4), including three bisnorditerpenes and 13 farnesylacetone derivatives, were obtained from the Sargassaceae family.Among them, 13 were from Sargassum sp., while one was from Cystophora sp.
Compounds 4-6, three novel bisnorditerpene isomers featuring an unusual α, β-unsaturated ketone skeleton, were isolated from S. hemiphyllum, collected from the Heda coast of the Izu Peninsula, Japan.They appeared to originate from the geranyl geraniol precursor and showed low cytotoxicity against P388 cells [32].
Terpenoids, a class of predominantly secondary metabolites, have been discovered in the Sargassaceae family [25,26].Specifically, 223 novel terpenoids have been obtained from five different Sargassacean genera, namely Cystoseira, Sargassum, Cystophora, Bifur caria, and Turbinaria.Based on the number of isoprene units and the biosynthesis pathway these isolated compounds can be categorized into monoterpenoids, sesquiterpenoids diterpenoids, triterpenes, and meroterpenes.

Norditerpenoids
Sixteen new norditerpenoid compounds (Figure 4), including three bisnorditerpenes and 13 farnesylacetone derivatives, were obtained from the Sargassaceae family.Among them, 13 were from Sargassum sp., while one was from Cystophora sp.
Compounds 4-6, three novel bisnorditerpene isomers featuring an unusual α, β-un saturated ketone skeleton, were isolated from S. hemiphyllum, collected from the Heda coast of the Izu Peninsula, Japan.They appeared to originate from the geranyl geranio precursor and showed low cytotoxicity against P388 cells [32].

Norditerpenoids
Sixteen new norditerpenoid compounds (Figure 4), including three bisnorditerpenes and 13 farnesylacetone derivatives, were obtained from the Sargassaceae family.Among them, 13 were from Sargassum sp., while one was from Cystophora sp.
Compounds 4-6, three novel bisnorditerpene isomers featuring an unusual α, βunsaturated ketone skeleton, were isolated from S. hemiphyllum, collected from the Heda coast of the Izu Peninsula, Japan.They appeared to originate from the geranyl geraniol precursor and showed low cytotoxicity against P388 cells [32].
Compounds 17-19, also classified as farnesylacetone derivatives belonging to norditerpenoid analogs, were obtained from the brown alga C. moniliformis, which was harvested from Port Philip Bay, Australia [35].Particularly, compounds 18 and 19 were two epimers that were indirectly formed from geranyl acetone [35].
Compounds 17-19, also classified as farnesylacetone derivatives belonging to norditerpenoid analogs, were obtained from the brown alga C. moniliformis, which was harvested from Port Philip Bay, Australia [35].Particularly, compounds 18 and 19 were two epimers that were indirectly formed from geranyl acetone [35].

Hydroazulene Diterpenoids
Four new diterpenoids, 63-66 (Figure 8), featuring a hydroazulene skeleton, were isolated from the brown alga C. myrica, collected at El-Zafrana, Gulf of Suez, Egypt.Their structures were determined by spectroscopic and chemical techniques.The cytotoxicities of these four compounds were tested in vitro against three different mouse cell lines (NIH3T3, SSVNIH3T3, and KA3IT).The results showed moderate cytotoxicity of all isolates against the cancer cell line KA3IT [52].Four new diterpenoids, 63-66 (Figure 8), featuring a hydroazulene skeleton, were isolated from the brown alga C. myrica, collected at El-Zafrana, Gulf of Suez, Egypt.Their structures were determined by spectroscopic and chemical techniques.The cytotoxicities of these four compounds were tested in vitro against three different mouse cell lines (NIH3T3, SSVNIH3T3, and KA3IT).The results showed moderate cytotoxicity of all isolates against the cancer cell line KA3IT [52].

Hydroazulene Diterpenoids
Four new diterpenoids, 63-66 (Figure 8), featuring a hydroazulene skeleton isolated from the brown alga C. myrica, collected at El-Zafrana, Gulf of Suez, Egypt structures were determined by spectroscopic and chemical techniques.The cytotox of these four compounds were tested in vitro against three different mouse cel (NIH3T3, SSVNIH3T3, and KA3IT).The results showed moderate cytotoxicity of lates against the cancer cell line KA3IT [52].

Xenicane Diterpenoids
A new xenicane-type diterpenoid, 67 (Figure 9), was isolated from the organic of the intertidal brown alga S. ilicifolium, which was harvested from the Gulf of M coast, India.This new metabolite, deduced as sargilicixenicane, showed potentia inflammatory and antioxidant activities [53].

Nor-Dammarane Triterpenoids
Two new nor-dammarane triterpenes, decurrencylics A-B (68 and 69) (Figu were isolated from the brown alga T. decurrens, which was harvested from the Mand region in the Gulf of Mannar, Peninsular India, India.Their structures were deter by extensive spectra analysis.The two compounds showed potent anti-inflammat tivities [54].

Xenicane Diterpenoids
A new xenicane-type diterpenoid, 67 (Figure 9), was isolated from the organic extract of the intertidal brown alga S. ilicifolium, which was harvested from the Gulf of Manner coast, India.This new metabolite, deduced as sargilicixenicane, showed potential antiinflammatory and antioxidant activities [53].

Hydroazulene Diterpenoids
Four new diterpenoids, 63-66 (Figure 8), featuring a hydroazulene skeleton, were isolated from the brown alga C. myrica, collected at El-Zafrana, Gulf of Suez, Egypt.Their structures were determined by spectroscopic and chemical techniques.The cytotoxicities of these four compounds were tested in vitro against three different mouse cell lines (NIH3T3, SSVNIH3T3, and KA3IT).The results showed moderate cytotoxicity of all isolates against the cancer cell line KA3IT [52].

Xenicane Diterpenoids
A new xenicane-type diterpenoid, 67 (Figure 9), was isolated from the organic extract of the intertidal brown alga S. ilicifolium, which was harvested from the Gulf of Manner coast, India.This new metabolite, deduced as sargilicixenicane, showed potential antiinflammatory and antioxidant activities [53].

Nor-Dammarane Triterpenoids
Two new nor-dammarane triterpenes, decurrencylics A-B (68 and 69) (Figure 10), were isolated from the brown alga T. decurrens, which was harvested from the Mandapam region in the Gulf of Mannar, Peninsular India, India.Their structures were determined by extensive spectra analysis.The two compounds showed potent anti-inflammatory activities [54].

Nor-Dammarane Triterpenoids
Two new nor-dammarane triterpenes, decurrencylics A-B (68 and 69) (Figure 10), were isolated from the brown alga T. decurrens, which was harvested from the Mandapam region in the Gulf of Mannar, Peninsular India, India.Their structures were determined by extensive spectra analysis.The two compounds showed potent anti-inflammatory activities [54].

Hydroazulene Diterpenoids
Four new diterpenoids, 63-66 (Figure 8), featuring a hydroazulene skeleton, were isolated from the brown alga C. myrica, collected at El-Zafrana, Gulf of Suez, Egypt.Their structures were determined by spectroscopic and chemical techniques.The cytotoxicities of these four compounds were tested in vitro against three different mouse cell lines (NIH3T3, SSVNIH3T3, and KA3IT).The results showed moderate cytotoxicity of all isolates against the cancer cell line KA3IT [52].

Xenicane Diterpenoids
A new xenicane-type diterpenoid, 67 (Figure 9), was isolated from the organic extract of the intertidal brown alga S. ilicifolium, which was harvested from the Gulf of Manner coast, India.This new metabolite, deduced as sargilicixenicane, showed potential antiinflammatory and antioxidant activities [53].

Nor-Dammarane Triterpenoids
Two new nor-dammarane triterpenes, decurrencylics A-B (68 and 69) (Figure 10), were isolated from the brown alga T. decurrens, which was harvested from the Mandapam region in the Gulf of Mannar, Peninsular India, India.Their structures were determined by extensive spectra analysis.The two compounds showed potent anti-inflammatory activities [54].13), consisting of an aromatic or substituted aromatic nucleus connected to a terpenoid chain with different degrees of oxidation, were isolated from Sargassaceae species .According to the structural characteristics, meroterpenoids can be classified into terpenyl-quinones/hydroquinone analogs, chromenes, and nahocols/isonahocols. Terpenyl-Quinones/Hydroquinone Analogs Ninety-six novel terpenyl-quinones/hydroquinones (70-165) (Figure 11), which consist of a quinone or hydroquinone nucleus connected to a terpenyl moiety, were isolated from three Sargassacean genera, namely Cystoseira, Sargassum, and Cystophora.
Two novel meroditerpenoids (90 and 91) were obtained from the brown alga C. baccata collected on the Moroccan Atlantic coast.They share the same trans-fusion bicyclic [4.3.0]nonane ring system, making the first instance of such a system reported from marine Sargassaceae algae [63].
A novel tetraprenylhydroquinol, balearone (94), was isolated from the chloroform extract of the brown alga C. balearica, collected at Portopalo, Sicily, Italy.Its chemical structure was deduced by single-crystal X-ray diffraction analysis [66].
A pair of novel tetraprenyltoluquinol isomers, 136 and 137, were isolated from the brown alga C. sauvageuana, collected at Aci Castello, Sicily, Italy.It was determined that 136 could be converted into 137 after photoisomerization [78].
Two new meroditerpenoids, fallahydroquinone (139) and fallaquinone (140), were isolated from the brown alga S. fallax, collected from Port Philip Bay, Victoria, Australia [80].Compound 140 is likely to be an artifact compound, as it could be produced from 139 by oxidation upon exposure to air.The absolute stereochemistry for 139 and 140 could not be established, owing to their instability and rapid decomposition.The two isolates displayed weak antitumor activities in a P388 assay [80].
Three new meroterpenoids, macrocarquinoids A-C (141-143), were isolated from the EtOH extract of the brown alga S. macrocarpum, harvested on the coast of Tsukumo Bay, Japan.Compound 142 possesses a γ-lactone ring at C-9 ′ to C-11 ′ and C-18 ′ of the terpenyl chain, while 143 has a δ-lactone ring at C-11 ′ to C-14 ′ and C-18 ′ [81].All of these compounds showed inhibitory activity against AGE that were either comparable to, or more potent than, activity of aminoguanidine, which was used as a positive control [81].
Four new plastoquinones 144-147 were isolated from the brown alga S. micracanthum, collected from the Toyama Bay coast of Japan.Their structures were determined by spectroscopic analysis and chemical conversions.Compounds 144-146 showed both antioxidant and cytotoxic activities [82].
Four new meroditerpenoids-sargahydroquinal (148), paradoxhydroquinone (149), paradoxquinol (150), and paradoxquinone (151)-were isolated from the brown alga S. paradoxum, collected from Governor Reef near Indented Head, Port Philip Bay, Australia.They consisted of a diterpenoid chain attached to hydroquinone or p-benzoquinone rings.Their structures were determined by spectroscopic techniques.Particularly, 148 was identified by HPLC-NMR and HPLC-MS, coupled with comparison with the known compound due to its instability.Compounds 149-151 showed weak antibacterial activities against Streptococcus pyogenes [83].
Two new meroditerpenoids (157 and 158) were isolated from the brown alga S. siliquastrum, collected from Jeju Island, Korea [86].Compound 157, a derivative of sargahydro-quinoic acid, exhibited significant radical-scavenging activity as well as slight inhibitory activity against isocitrate lyase from Candida albicans.The stereochemistry at C-13 ′ of 157 remained uncertain due to the limited quantity.Compound 158, representing the first reported meroditerpenoid with a modified dihydroquinone unit from marine brown algae, exhibited weak activity against transpeptidase sortase A from Staphylococcus aureus [86].Interestingly, 158 was presumed to be a biosynthetic precursor of nahocols and isonahocols, based on a 1,3-migration of its methyl acetate group.
Seven new geranylgeranylbenzoquinone derivatives (159-165) were separated from the Japanese marine alga S. tortile harvested at Awa-Kominato, Chiba, Japan.These isolates consist of a hydroquinone or benzoquinone core linked to a diterpenoid moiety.Among them, compounds 159/160 and 162/163 constitute two pair of isomers.Compound 161 could be converted into quinone 164 by selective oxidation [87].

Chromenes
Forty-nine new chromene meroterpenods (Figure 12) were isolated from certain species of Sargassaceae.Their structures are similar to that of vitamin E.
Three new chromane meroditerpenes (174-176) were isolated from the previously mentioned unidentified Cystoseira specimen.Due to their inherent instability, 175 and 176 were only obtained in the acetate form.In particular, 175 represented the first example of meroditerpene containing a newly rearranged structure, featuring a novel ether linkage in the diterpene chain.The structure is likely formed from 176 via an oxidation process of the enol-ether system, followed by rearrangement [64].
A new phloroglucinol-meroditerpenoid hybrid (177), consisting of a chromane meroditerpenoid linked to a phloroglucinol through a 2,7-dioxabicylo [3.2.1] octane unit, was isolated from the brown alga C. tamariscifolia mentioned above.This isolate showed

Chromenes
Forty-nine new chromene meroterpenods (Figure 12) were isolated from certain species of Sargassaceae.Their structures are similar to that of vitamin E.
Three new chromane meroditerpenes (174-176) were isolated from the previously mentioned unidentified Cystoseira specimen.Due to their inherent instability, 175 and 176 were only obtained in the acetate form.In particular, 175 represented the first example of meroditerpene containing a newly rearranged structure, featuring a novel ether linkage in the diterpene chain.The structure is likely formed from 176 via an oxidation process of the enol-ether system, followed by rearrangement [64].
A new phloroglucinol-meroditerpenoid hybrid (177), consisting of a chromane meroditerpenoid linked to a phloroglucinol through a 2,7-dioxabicylo [3.2.1] octane unit, was isolated from the brown alga C. tamariscifolia mentioned above.This isolate showed moderate to weak antifouling activities against several marine colonizing species such as bacteria, fungi, micro-and macroalgae [73].
A new chromene meroditerpenoid, fallachromenoic acid (178), featuring a carboxylic group and a chlorine atom, was isolated from the brown alga S. fallax described above.Its absolute configuration could not be assigned due to its instability [80].Compound 178 showed weak antitumor activity against P388 murine leukemia cells [80].
Two new chromane meroterpenoids (179 and 180) were obtained from the brown alga S. micracanthum, harvested on the Toyama Bay coast, Japan.Their structures were determined by extensive spectroscopic analysis and chemical conversion [91].
Two new chromene meroditerpenoids (181 and 182), characterized by a lactone ring, were isolated from the Japanese alga S. sagamianum mentioned above [84].Their structures were determined by extensive spectrometric analysis and comparison with published data.Particularly, 181 exhibited antibacterial and weak cytotoxic activities [84].
A novel furanyl-substituted isochromanyl derivative, turbinochromanone (207), was isolated from the ethyl acetate-methanolic extract of the brown seaweed Turbinaria conoides, collected from the coasts of Peninsular India.Compound 207 exhibited potential attenuation properties against 5-lipoxygenase and cyclooxygenase-2-enzyme.Furthermore, its antioxidant properties supported its potential use as an anti-inflammatory agent [97].
Two new tetraprenyltoluquinol isomers, thunbergol A (208) and B (209), were obtained from the brown alga S. thunbergii collected along the Busan coast of Korea.The two compounds showed antioxidant effects against DPPH radical and authentic/induced ONOO − [98].

Nahocols/Isonahocols
Five new nahocols (215-219) and four novel isonahocols (220-223) were isolated from the brown alga S. siliquastrum mentioned above [86,102].Their structures are shown in Figure 13.They share structural similarities to 158 [86].Especially, 219 contains a cyclopentenone moiety, the characteristic cyclization pattern of which has only been reported for the second time in marine algae.All of them exhibited radical-scavenging activity against DPPH free radicals.Furthermore, isonahocols 220-223 showed a 100-fold increase in radical-scavenging activities compared with nahocols 215-219, indicating the crucial role of the phenolic group in DPPH radical scavenging activity.In addition, 215-219 showed still-weak activities against isocitrate lyase from Candida albicans, while 220-223 exhibited inhibitory effects on transpeptidase sortase A derived from Staphylococcus aureus.
Compound 227, consisting of a hydroxyphloroglucinol unit and a sargassumketone moiety, was obtained from the brown alga S. micracanthum, collected at Wando County, Korea.It showed radical-scavenging activity against ABTS + radicals [106].
Compound 228, containing a phloroglucinol unit and an ascorbic acid moiety, was isolated from the ethanolic extract of the brown alga S. spinuligerum as a novel phloroglucinol derivate.Its stereochemistry was determined through NOE experiments and molecular modeling [107].
Compound 227, consisting of a hydroxyphloroglucinol unit and a sargassumketone moiety, was obtained from the brown alga S. micracanthum, collected at Wando County, Korea.It showed radical-scavenging activity against ABTS + radicals [106].
Compound 228, containing a phloroglucinol unit and an ascorbic acid moiety, was isolated from the ethanolic extract of the brown alga S. spinuligerum as a novel phloroglucinol derivate.Its stereochemistry was determined through NOE experiments and molecular modeling [107].
moiety, was obtained from the brown alga S. micracanthum, collected at Wando County, Korea.It showed radical-scavenging activity against ABTS + radicals [106].
Compound 228, containing a phloroglucinol unit and an ascorbic acid moiety, was isolated from the ethanolic extract of the brown alga S. spinuligerum as a novel phloroglucinol derivate.Its stereochemistry was determined through NOE experiments and molecular modeling [107].

Fucophlorethols
Twenty-three new phloroglucinol derivatives (229-251) (Figure 15), belonging to the class of fucophlorethols with three to fourteen rings, were isolated from three distinct Sargassaceae species, namely Carpophyllum maschalocarpum, S. spinuligerum, and Cystophora torulosa.Among these, 229-234 were obtained from the brown alga C. maschalocarpum collected at Torbay, north of Auckland, New Zealand [108].Interestingly, 234 is the largest fucophlorethol, characterized by 14 phloroglucinol units.Due to the presence of extra hydroxyl groups, 229, 231, and 233 were also categorized as hydroxyfucophlorethols.

Hydroxyphlorethols
Five new phloroglucinol derivatives belonging to the class of hydroxyphlorethols, 252-256 (Figure 16), were isolated from two Carpophyllum species, namely C. maschalocarpum and C. angustifolium [112,113].Specifically, 252 and 253, which contain an additional hydroxyl group, were isolated from the brown alga C. maschalocarpum collected at Torbay, north of Auckland [112].
Compounds 254-256 feature three additional hydroxyl groups as well as two 1,2diphoxylated 3,4,5-triacetoxybenzene rings linked by an ether bond, leading to their designation as trihydroxyphlorethols.All of them were isolated from the brown alga C. angustifolium harvested at Panetiki Island, Cape Rodney [113].

Carmalols
Two new phloroglucinol derivatives belonging to the class of carmalols (257 and 258) (Figure 17) were isolated from the brown alga C. maschalocarpum mentioned above [112,114].Compound 257 contains two phloroglucinol units and an additional hydroxyl group, and it was named diphlorethohydroxycarmalol nonaacetate.Meanwhile, 258, which possesses three phloroglucinol units and one additional hydroxyl group, was designated as triphlorethohydroxycarmalol undecaacetate [114].

Fuhalols and Others
A new phloroglucinol derivative belonging to the class of fuhalols, 262 (Figure 19), together with two new phlorotannins with a chlorine atom (263 and 264), were isolated from the brown alga C. angustifolium, collected at Panetike Island/Cape Rodney/New Zealand [115].Among them, 262 consists of eight phloroglucinol units linked by ether bonds and contains additional hydroxyl groups.Compound 263 is a chlorinated bifuhalol derivative, whereas 264 is a chlorinated difucol derivative.
In addition, a new phloroglucinol derivative, DDBT (265) (Figure 19), was isolated from the brown alga S. patens, harvested from the coast of the Noto Peninsula, Japan.This compound showed inhibitory effects against α-amylase and α-glucosidase [116].Zealand [115].Among them, 262 consists of eight phloroglucinol units linked by ether bonds and contains additional hydroxyl groups.Compound 263 is a chlorinated bifuhalol derivative, whereas 264 is a chlorinated difucol derivative.
In addition, a new phloroglucinol derivative, DDBT (265) (Figure 19), was isolated from the brown alga S. patens, harvested from the coast of the Noto Peninsula, Japan.This compound showed inhibitory effects against α-amylase and α-glucosidase [116].
Compound 266, a C27-brassinosteroid with two keto groups and a hydroxy group, was isolated from the brown alga C. myrica, harvested from the region of Fayed, Egypt.It represented the first report of brassinosteroid analogs derived from seaweed.Compound 266 showed cytotoxic effects against HEPG-2 and HCT116 cell lines [117].
Compound 267, a C29-steroid with an α, β-unsaturated carbonyl group and a tertiary hydroxyl group, was isolated from the brown alga S. asperifolium, collected at Hurghada, Egypt.From a biosynthetic perspective, 267 could potentially be derived from saringosterol via an oxidation process involving 3β-OH, followed by the formation of an α, β-unsaturated ketone [118].
Compounds 268 and 269, two polyoxygenated steroids, were isolated from the brown alga S. carpophyllum, harvested from the coasts of the South China Sea in Beihai,
Compound 266, a C27-brassinosteroid with two keto groups and a hydroxy group, was isolated from the brown alga C. myrica, harvested from the region of Fayed, Egypt.It represented the first report of brassinosteroid analogs derived from seaweed.Compound 266 showed cytotoxic effects against HEPG-2 and HCT116 cell lines [117].
Compound 267, a C29-steroid with an α, β-unsaturated carbonyl group and a tertiary hydroxyl group, was isolated from the brown alga S. asperifolium, collected at Hurghada, Egypt.From a biosynthetic perspective, 267 could potentially be derived from saringosterol via an oxidation process involving 3β-OH, followed by the formation of an α, β-unsaturated ketone [118].
Compounds 268 and 269, two polyoxygenated steroids, were isolated from the brown alga S. carpophyllum, harvested from the coasts of the South China Sea in Beihai, China.Specifically, 268 is a C29-polyoxygenated steroid, while 269 is a C27-dinorsteroid, representing only the second example of ring A-dinorsteroid analogs found in natural or-
Compound 266, a C 27 -brassinosteroid with two keto groups and a hydroxy group, was isolated from the brown alga C. myrica, harvested from the region of Fayed, Egypt.It represented the first report of brassinosteroid analogs derived from seaweed.Compound 266 showed cytotoxic effects against HEPG-2 and HCT116 cell lines [117].
Compound 267, a C 29 -steroid with an α, β-unsaturated carbonyl group and a tertiary hydroxyl group, was isolated from the brown alga S. asperifolium, collected at Hurghada, Egypt.From a biosynthetic perspective, 267 could potentially be derived from saringosterol via an oxidation process involving 3β-OH, followed by the formation of an α, β-unsaturated ketone [118].
Compounds 268 and 269, two polyoxygenated steroids, were isolated from the brown alga S. carpophyllum, harvested from the coasts of the South China Sea in Beihai, China.Specifically, 268 is a C 29 -polyoxygenated steroid, while 269 is a C 27 -dinorsteroid, representing only the second example of ring A-dinorsteroid analogs found in natural organisms.Both compounds could induce morphological abnormalities of Pyricularia oryzae mycelia.In addition, 268 exhibited cytotoxic activity against HL-60 cell lines [119].
Compounds 270 and 271 are two cholestane-type sterols, each featuring an α, βunsaturated ketone moiety.Among them, 270 is a C 27 -steroid, while 271 is a C 29 -steroid.Both were isolated from the brown alga S. fusiforme, harvested from Anhui Bozhou Xiancheng Pharmaceutical Limited Company of China.Their absolute configurations were determined by comparing the calculated and experimental ECD spectra [120].
Compound 272, a stigmastane-type sterol characterized by three double bonds and one hydroxyl group, was isolated from the brown alga S. polycystcum, collected from the North China Sea, China [121].
Compound 273, a tri-unsaturated C 29 -sterol with a 3β-hydroxy-∆ 5 -steroid skeleton and a vinyloxy group, was isolated from the brown alga S. thumbergii, harvested at Muroran, Japan.Its structure was determined by combining NMR spectroscopy and chemical conversion [122].
Compound 274, a C 29 -sterol with a 3-hydroxy-2,5-dien-4-carbonyl fragment, was isolated from the brown alga S. thunbergii, harvested along the coasts of Nanji Island in the East China Sea of China.It was the first sterol example discovered to contain a 3-hydroxy-2,5-dien-4-carbonyl moiety.Compound 274 showed significant inhibitory activity against PTP1B with an IC 50 of 2.24 µg/mL [123].
Compounds 275-282, which are oxygenated steroids, were isolated from two separate samples of Turbinaria conoides, one collected at Salin Munthal (India) [124] and another at the coast of Kenting (Taiwan).Notably, 276 is identified as a cardenolide-type C 23 steroid with an aromatic ring, while the remaining compounds are either stigmasterol or fucosterol derivatives, comprised of 29 carbons.Compounds 275 and 276 showed antimicrobial activities [124], whereas 279-282 exhibited cytotoxic effects against cancer cell lines P-388, KB, A-549, and HT-29 [125].Pharmaceutical Limited Company of China.Their absolute configurations were determined by comparing the calculated and experimental ECD spectra [120].
Compound 272, a stigmastane-type sterol characterized by three double bonds and one hydroxyl group, was isolated from the brown alga S. polycystcum, collected from the North China Sea, China [121].
Compound 273, a tri-unsaturated C29-sterol with a 3β-hydroxy-Δ 5 -steroid skeleton and a vinyloxy group, was isolated from the brown alga S. thumbergii, harvested at Muroran, Japan.Its structure was determined by combining NMR spectroscopy and chemical conversion [122].
Two new aryl cresol isomers (302 and 303) were isolated from the brown alga S. cinereum, harvested along the coasts of the Red Sea in Hurghada, Egypt.Interestingly, the two isolates showed antiproliferative activities against certain cancer cell lines and inhibitory effects against 5-LOX and 15-LOX, the enzymes that have a vital effect on the viability of tumor cells [134].
A novel ketone hybrid of mix biogenesis (304), consisting of a four-carbon chain attached to a hydroquinol ring, was isolated from the aforementioned brown alga C. abies [60].Its structure was determined by spectroscopic analysis, including NMR, MS, and UV.
A new amide derivative, sargassulfamide A (305), was obtained from the brown alga S. naozhouense, harvested from the Leizhou Peninsula, China.Its structure was established by spectrometric analysis and single-crystal X-ray diffraction [135].

Conclusions
The merging of the former Cystoseiraceae and Sargassaceae families has resulted in Sargassaceae becoming the largest family in Fucale.To date, more than 60 species of Sargassaceae have been chemically studied, leading to the identification of more than 400 metabolites.Based the available literature, this review summarizes a total of 307 new compounds obtained from 44 Sargassaceae species spanning six genera, and newly discovered compounds derived from the 44 species collected from diverse locations along the Tunisian, Chinese, Italian, Japanese, Australian, Moroccan, Irish Atlantic, Spanish, French, Indian, Egyptian, Portuguese, Algerian, Korean, and New Zealand coasts (Table 1).These include 223 terpenoids, 42 phloroglucinols, 17 steroids, and 25 other types of compounds.

Conclusions
The merging of the former Cystoseiraceae and Sargassaceae families has resulted in Sargassaceae becoming the largest family in Fucale.To date, more than 60 species of Sargassaceae have been chemically studied, leading to the identification of more than 400 metabolites.Based the available literature, this review summarizes a total of 307 new compounds obtained from 44 Sargassaceae species spanning six genera, and newly discovered compounds derived from the 44 species collected from diverse locations along the Tunisian, Chinese, Italian, Japanese, Australian, Moroccan, Irish Atlantic, Spanish, French, Indian, Egyptian, Portuguese, Algerian, Korean, and New Zealand coasts (Table 1).These include 223 terpenoids, 42 phloroglucinols, 17 steroids, and 25 other types of compounds.

Species Sampling Locations Compounds and Types
Ref.

S. micracanthum
The majority of the secondary metabolites are meroterpenoids, diterpenoids, and phloroglucinols (Figure 22).Sargassum and Cystoseira are the most studied genera, reported by 42 and 27 articles, respectively, and are rich in meroterpenoids (Figure 23).Bifurcaria, investigated in 15 articles, is rich in linear diterpenoids, followed by Turbinaria, Cystophora, and Carpophyllum, which were discussed by eight, five, and five articles, respectively.Notably, the most productive species were B. bifurcata and S. siliquastrum, which have yielded 39 and 35 new compounds, respectively.They were followed by C. usneoides, C. crinita and S. micracanthum, which produced 22, 18, and 17 new compounds, respectively (Table 1).

Carpophyllum maschalocarpum
Torbay  [113,115] The majority of the secondary metabolites are meroterpenoids, diterpenoids, and phloroglucinols (Figure 22).Sargassum and Cystoseira are the most studied genera, reported by 42 and 27 articles, respectively, and are rich in meroterpenoids (Figure 23).Bifurcaria, investigated in 15 articles, is rich in linear diterpenoids, followed by Turbinaria, Cystophora, and Carpophyllum, which were discussed by eight, five, and five articles, respectively.Notably, the most productive species were B. bifurcata and S. siliquastrum, which have yielded 39 and 35 new compounds, respectively.They were followed by C. usneoides, C. crinita and S. micracanthum, which produced 22, 18, and 17 new compounds, respectively (Table 1).Notably, from a chemical viewpoint, B. bifurcata is clearly distinguis Sargassaceae species due to its extensive production of linear diterpenes remaining species, with the exception of C. crinita, do not produce acyc Interestingly, the linear diterpenes yielded by C. crinita belong to monoygenated geranylgeraniol derivatives with the oxygenated function locat or C-10, depending on the specific sampling locations.

Figure 15 .
Figure 15.Phloroglucinol derivatives belonging to the class of fucophlorethols.

Figure 16 .
Figure 16.Phloroglucinol derivatives belonging to the class of hydroxyphlorethols.

Figure 16 .
Figure 16.Phloroglucinol derivatives belonging to the class of hydroxyphlorethols.Figure 16.Phloroglucinol derivatives belonging to the class of hydroxyphlorethols.

Figure 16 .
Figure 16.Phloroglucinol derivatives belonging to the class of hydroxyphlorethols.Figure 16.Phloroglucinol derivatives belonging to the class of hydroxyphlorethols.

Figure 16 .
Figure 16.Phloroglucinol derivatives belonging to the class of hydroxyphlorethols.

Figure 17 .
Figure 17.Phloroglucinol derivatives belonging to the class of carmalols.Figure 17.Phloroglucinol derivatives belonging to the class of carmalols.

Figure 19 .
Figure 19.Phloroglucinol derivatives belonging to the class of fuhalols and others.

Figure 19 .
Figure 19.Phloroglucinol derivatives belonging to the class of fuhalols and others.

Figure 19 .
Figure 19.Phloroglucinol derivatives belonging to the class of fuhalols and others.

Figure 21 .
Figure 21.Other types of compounds isolated from Sargassacean species.

Figure 23 .
Figure 23.Numbers of compounds and publications from Sargassacean genus.

Table 1 .
Chemical compounds studied in the Sargassaceae species in this review.Figure 21.Other types of compounds isolated from Sargassacean species.

Table 1 .
Chemical compounds studied in the Sargassaceae species in this review.