Search Results (37)

This article presents a comprehensive overview of recent discoveries and advancements in the field of steroid chemistry, highlighting the isolation and characterization of various steroidal compounds from natural sources. This paper discusses a wide range of steroids, including pregnane steroids, steroidal alkaloids, ketosteroids, and novel triterpenoids, derived from marine organisms, fungi, and plants. Significant findings include the isolation of bioactive compounds such as the cytotoxic erectsterates from microorganisms, soft corals, the unusual tetracyclic steroid penicillitone from a fungal culture, and innovative steroidal derivatives with potential anti-inflammatory and anticancer activities. The synthesis of steroids from microorganisms as a tool for pharmaceutical development is also explored, showcasing the role of microbial biotransformation in generating steroidal drugs. Additionally, this paper emphasizes the ecological and medicinal relevance of these compounds, which are often used in traditional medicine and have potential therapeutic applications in treating diseases like cancer and microbial infections. This article serves as a vital resource for researchers interested in the chemical diversity of steroids and their applications in drug discovery and development. Full article

An Aspergillus fumigatus KMM 4631 strain was previously isolated from a Pacific soft coral Sinularia sp. sample and was found to be a source of a number of bioactive secondary metabolites. The aims of this work are the confirmation of this strain’ identification based on ITS, BenA, CaM, and RPB2 regions/gene sequences and the investigation of secondary metabolite profiles of Aspergillus fumigatus KMM 4631 culture and its co-cultures with Penicillium hispanicum KMM 4689, Amphichorda sp. KMM 4639, Penicillium sp. KMM 4672, and Asteromyces cruciatus KMM 4696 from the Collection of Marine Microorganisms (PIBOC FEB RAS, Vladivostok, Russia). Moreover, the DPPH-radical scavenging activity, urease inhibition, and cytotoxicity of joint fungal cultures’ extracts on HepG2 cells were tested. The detailed UPLC MS qTOF investigation resulted in the identification and annotation of indolediketopiperazine, quinazoline, and tryptoquivaline-related alkaloids as well as a number of polyketides (totally 20 compounds) in the extract of Aspergillus fumigatus KMM 4631. The metabolite profiles of the co-cultures of A. fumigatus with Penicillium hispanicum, Penicillium sp., and Amphichorda sp. were similar to those of Penicillium hispanicum, Penicillium sp., and Amphichorda sp. monocultures. The metabolite profile of the co-culture of A. fumigatus with Asteromyces cruciatus differed from that of each monoculture and may be more promising for the isolation of new compounds. Full article

Sinulariolide (SC-1) is a natural product extracted from the cultured-type soft coral Sinularia flexibilis and possesses anti-inflammation, anti-proliferative, and anti-migratory in several types of cancer cells. However, the molecular pathway behind its effects on inflammation remains poorly understood. Since inflammatory cytokines such as TGFβ, TNFα, IL-1, IL-6, and IL-8 activate transcription factors such as Smads, NF-κB, STAT3, Snail, Twist, and Zeb that drive the epithelial-to-mesenchymal transition (EMT), in this study, we focus on the investigation in effects of SC-1 on TGFβ-induced interleukin-6 (IL-6) releases in an in vitro cell culture model. We showed that both intracellular IL-6 expression and secretion were stimulated by TGFβ and associated with strong upregulation of IL-6 mRNA and increased transcription in A549 cells. SC-1 blocked TGFβ-induced secretion of IL-6 while showing no effect on the induction of fibronectin and plasminogen activator inhibitor-1 genes, indicating that SC-1 interferes with only a subset of TGFβ activities. In addition, SC-1 inhibits TGFβ-induced IL-6 by suppressing p38 MAPK signaling and subsequently inhibits NF-κB and its nuclear translocation without affecting the canonical Smad pathway and receptor turnover. Overall, these data suggest that p38 may involve in the inhibition of SC-1 in IL-6 release, thus illustrating an inhibitory effect for SC-1 in the suppression of inflammation, EMT phenotype, and tumorigenesis. Full article

The chemical screening of a cultured soft coral, Briareum violaceum, led to the isolation of eight natural, briarane-related diterpenoids, including three unreported metabolites, briavioids E–G (1–3), and five known briaranes, briacavatolides B (4) and C (5), briaexcavatin L (6), briaexcavatolide U (7) and briarenol K (8). The structures of briaranes 1–8 were established using spectroscopic methods. The absolute configuration of briavioid A (9), obtained in a previous study, was reported for the first time in this study by a single-crystal X-ray diffraction analysis using a copper radiation source. The anti-inflammatory activity of briaranes 1 and 2 and briaranes 4–8 was evaluated by screening their inhibitory ability against the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. Full article

Biscembranoids are the distinctive tetraterpenoids owing a 14/6/14 membered tricyclic scaffold that have been mainly discovered in the soft corals, especially the genera Sarcophyton, Lobophytum and Sinularia. Recent findings have demonstrated the great anti-inflammatory potential of biscembranoid analogues in human neutrophils, motivating more chemical and biological explorations targeting these marine-derived natural products. In the current study, the chemical diversity of biscembranoids derived from the cultured-type Sarcophyton trocheliophorum von Marenzeller was illustrated through MS/MS molecular networking (MN) profiling approach. Based on the MN patterns, the prioritization of unknown biscembranoid derivatives was putatively analyzed. As a result, the biscembrane targeting isolation afforded two new metabolites, sarcotrochelides A (1) and B (2), along with six known analogues (3–8). Their structures and relative configurations were determined by spectroscopic methods. In vitro neutrophil inflammatory inhibition was further investigated for all isolates based on reduced superoxide anion (O₂^•−) generation detections. Compounds 5–8 showed significant dose-dependently inhibitory effects, suggesting the cruciality of 6,7-dihydrooxepin-2(5H)-one moiety and saturated γ-lactone ring in their reactive oxygen species (ROS)-dependent anti-inflammatory properties. Full article

Malaria is a persistent illness with a great public health concern. To combat this fatal disease, developing effective antimalarial medications has become a necessity. In the present study, we described the actinomycetes associated with the Red Sea soft coral Nephthea sp. and isolated a strain that was sub-cultured in three different media (M1, ISP2, and OLIGO). Actinomycete isolate’s phylogenetic analysis of the 16S rRNA gene revealed that it belongs to the genus Rhodococcus. In vitro screening of the antimalarial activity for three extracts against Plasmodium falciparum was carried out. Non-targeted metabolomics for the chemical characterization of the isolated actinomycete species UA111 derived extracts were employed using high-resolution liquid chromatography–mass spectrometry (LC-HR-MS) for dereplication purposes. Additionally, statistical analysis of the vast LC-MS data was performed using MetaboAnalyst 5.0. Finally, an in silico analysis was conducted to investigate the potential chemical compounds that could be the source of the antimalarial potential. The results revealed that ISP2 media extract is the most effective against Plasmodium falciparum, according to antimalarial screening (IC₅₀ 8.5 µg/mL), in contrast, OLIGO media extract was inactive. LC-HRMS-based metabolomics identified a range of metabolites, mainly alkaloids, from the genus Rhodococcus. On the other hand, multivariate analysis showed chemical diversity between the analyzed samples, with ISP2 extract being optimal. The docking analysis was able to anticipate the various patterns of interaction of the annotated compounds with three malarial protein targets (P. falciparum kinase, P. falciparum cytochrome bc1 complex, and P. falciparum lysyl-tRNA synthetase). Among all of the test compounds, perlolyrine (11) and 3097-B2 (12) displayed the best docking profiles. In conclusion, this work demonstrated the value of the established method for the metabolic profiling of marine actinomycetes using the data from liquid chromatography–mass spectrometry (LC-MS), which helps to streamline the difficult isolation stages required for their chemical characterization. In addition, the antimalarial efficacy of this strain has intriguing implications for future pharmaceutical development. Full article

In recent decades, aquaculture techniques for soft corals have made remarkable progress in terms of conditions and productivity. Researchers have been able to obtain larger quantities of soft corals, thus larger quantities of biologically active metabolites, allowing them to study their biological activity in many pharmacological assays and even produce sufficient quantities for clinical trials. In this review, we summarize 201 secondary metabolites that have been identified from cultured soft corals in the era from 2002 to September 2022. Various types of diterpenes (eunicellins, cembranes, spatanes, norcembranes, briaranes, and aquarianes), as well as biscembranes, sterols, and quinones were discovered and subjected to bioactivity investigations in 53 different studies. We also introduce a more in-depth discussion of the potential biological effects (anti-cancer, anti-inflammatory, and anti-microbial) and the mechanisms of action of the identified secondary metabolites. We hope this review will shed light on the untapped potential applications of aquaculture to produce valuable secondary metabolites to tackle current and emerging health conditions. Full article

Palytoxin (PLTX) is a highly toxic polyether identified in various marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. In addition to adverse effects in humans, negative impacts on different marine organisms have been often described during Ostreopsis blooms and the concomitant presence of PLTX and its analogues. Considering the increasing frequency of Ostreopsis blooms due to global warming, PLTX was investigated for its effects on Artemia franciscana, a crustacean commonly used as a model organism for ecotoxicological studies. At concentrations comparable to those detected in culture media of O. cf. ovata (1.0–10.0 nM), PLTX significantly reduced cysts hatching and induced significant mortality of the organisms, both at larval and adult stages. Adults appeared to be the most sensitive developmental stage to PLTX: significant mortality was recorded after only 12 h of exposure to PLTX concentrations > 1.0 nM, with a 50% lethal concentration (LC₅₀) of 2.3 nM (95% confidence interval = 1.2–4.7 nM). The toxic effects of PLTX toward A. franciscana adults seem to involve oxidative stress induction. Indeed, the toxin significantly increased ROS levels and altered the activity of the major antioxidant enzymes, in particular catalase and peroxidase, and marginally glutathione-S-transferase and superoxide dismutase. On the whole, these results indicate that environmentally relevant concentrations of PLTX could have a negative effect on Artemia franciscana population, suggesting its potential ecotoxicological impact at the marine level. Full article

Three novel cyclic hexapeptides, sclerotides C–E (1–3), and a new lipodepsipeptide, scopularide I (4), together with a known cyclic hexapeptide sclerotide A (5), were isolated from fermented rice cultures of a soft coral-derived fungus: Aspergillus sclerotiorum SCSIO 41031. The structures of the new peptides were determined by 1D and 2D NMR spectroscopic analysis, Marfey’s method, ESIMS/MS analysis, and single crystal X-ray diffraction analysis. Scopularide I (4) exhibited acetylcholinesterase inhibitory activity with an IC₅₀ value of 15.6 μM, and weak cytotoxicity against the human nasopharyngeal carcinoma cell line HONE-EBV with IC₅₀ value of 10.1 μM. Full article

Acne is a skin disease common in adolescents and increasingly common in the adult population. The major pathologic events of acne vulgaris include increased sebum production, retention hyperkeratosis, carrying commensal skin microbiota, and inflammation. In recent years, more than 10,000 compounds have been isolated and identified from marine organisms. The aim of this study was to discover the potential anti-acne activity of fraction 9 + 10 (SF-E) of Sinularia flexibilis extract and six cembrene diterpenoids. We found that the SF-E significantly reduced Cutibacterium acnes-induced edema in Wistar rat ears. The cembrene diterpenoids including 11-dehydrosinulariolide (SC-2), 3,4:8,11-bisepoxy-7-acetoxycembra-15(17)-en-1,12-olide (SC-7), and sinularin (SC-9) reduced nitric oxide (NO) production with 50% inhibitory concentration of 5.66 ± 0.19, 15.25 ± 0.25, and 3.85 ± 0.25 μM, respectively, and inducible NO synthase expression in RAW 264.7 cells. Moreover, treatment with SC-2, SC-7, and SC-9 significantly suppressed lipopolysaccharide- and heat-killed C. acnes-induced expression of proteins involved in mitogen-activated protein kinase pathway in both RAW 264.7 and HaCaT cells. After treatment with SC-2, SC-7, and SC-9, over-proliferation of HaCaT cells was significantly terminated. In summary, SC-2, SC-7, and SC-9 showed anti-inflammatory effects in RAW 264.7 cells, suggesting that these cembrene diterpenoids obtained from S. flexibilis are natural marine products with potential anti-acne activities. Full article

Chemical examination from the cultured soft coral Sarcophyton digitatum resulted in the isolation and structural identification of four new biscembranoidal metabolites, sardigitolides A–D (1–4), along with three previously isolated biscembranoids, sarcophytolide L (5), glaucumolide A (6), glaucumolide B (7), and two known cembranoids (8 and 9). The chemical structures of all isolates were elucidated on the basis of 1D and 2D NMR spectroscopic analyses. Additionally, in order to discover bioactivity of marine natural products, 1–8 were examined in terms of their inhibitory potential against the upregulation of inflammatory factor production in lipopolysaccharide (LPS)-stimulated murine macrophage J774A.1 cells and their cytotoxicities against a limited panel of cancer cells. The anti-inflammatory results showed that at a concentration of 10 µg/mL, 6 and 8 inhibited the production of IL-1β to 68 ± 1 and 56 ± 1%, respectively, in LPS-stimulated murine macrophages J774A.1. Furthermore, sardigitolide B (2) displayed cytotoxicities toward MCF-7 and MDA-MB-231 cancer cell lines with the IC₅₀ values of 9.6 ± 3.0 and 14.8 ± 4.0 µg/mL, respectively. Full article

Cancer metastasis is the main cause of death in cancer patients; however, there is currently no effective method to predict and prevent metastasis of gastric cancer. Therefore, gaining an understanding of the molecular mechanism of tumor metastasis is important for the development of new drugs and improving the survival rate of patients who suffer from gastric cancer. Sinulariolide is an active compound isolated from the cultured soft coral Sinularia flexibilis. We employed sinulariolide and gastric cancer cells in experiments such as MTT, cell migration assays, cell invasion assays, and Western blotting analysis. Analysis of cell migration and invasion capabilities showed that the inhibition effects on cell metastasis and invasion increased with sinulariolide concentration in AGS and NCI-N87 cells. Immunostaining analysis showed that sinulariolide significantly reduced the protein expressions of MMP-2, MMP-9, and uPA, but the expressions of TIMP-1 and TIMP-2 were increased, while FAK, phosphorylated PI3K, phosphorylated AKT, phosphorylated mTOR, phosphorylated JNK, phosphorylated p38MAPK, and phosphorylated ERK decreased in expression with increasing sinulariolide concentration. From the results, we inferred that sinulariolide treatment in AGS and NCI-N87 cells reduced the activities of MMP-2 and MMP-9 via the FAK/PI3K/AKT/mTOR and MAPKs signaling pathways, further inhibiting the invasion and migration of these cells. Moreover, sinulariolide altered the protein expressions of E-cadherin and N-cadherin in the cytosol and Snail in the nuclei of AGS and NCI-N87 cells, which indicated that sinulariolide can avert the EMT process. These findings suggested that sinulariolide is a potential chemotherapeutic agent for development as a new drug for the treatment of gastric cancer. Full article

Flaccidoxide-13-acetate, an active compound isolated from cultured-type soft coral Sinularia gibberosa, has been shown to have inhibitory effects against invasion and cell migration of RT4 and T24 human bladder cancer cells. In our study, we used an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation assay, and flow cytometry to determine the mechanisms of the anti-tumor effect of flaccidoxide-13-acetate. The MTT and colony formation assays showed that the cytotoxic effect of flaccidoxide-13-acetate on T24 and RT4 cells was dose-dependent, and the number of colonies formed in the culture was reduced with increasing flaccidoxide-13-acetate concentration. Flow cytometry analysis revealed that flaccidoxide-13-acetate induced late apoptotic events in both cell lines. Additionally, we found that flaccidoxide-13-acetate treatment upregulated the expressions of cleaved caspase 3, cleaved caspase 9, Bax, and Bad, and down-regulated the expressions of Bcl-2, p-Bad, Bcl-x1, and Mcl-1. The results indicated that apoptotic events were mediated by mitochondrial dysfunction via the caspase-dependent pathway. Flaccidoxide-13-acetate also provoked endoplasmic reticulum (ER) stress and led to activation of the PERK-eIF2α-ATF6-CHOP pathway. Moreover, we examined the PI3K/AKT signal pathway, and found that the expressions of phosphorylated PI3K (p-PI3K) and AKT (p-AKT) were decreased with flaccidoxide-13-acetate concentrations. On the other hand, our results showed that the phosphorylated JNK and p38 were obviously activated. The results support the idea that flaccidoxide-13-acetate-induced apoptosis is mediated by mitochondrial dysfunction, ER stress, and activation of both the p38 and JNK pathways, and also relies on inhibition of PI3K/AKT signaling. These findings imply that flaccidoxide-13-acetate has potential in the development of chemotherapeutic agents for human bladder cancer. Full article

11-Dehydrosinulariolide, an active compound that is isolated from the cultured soft coral Sinularia flexibilis, has been suggested to show anti-tumor biological characteristics according to previous studies. However, its potential effect on small cell lung cancer (SCLC) remains unknown. The present study investigates the underlying mechanism for the treatment of SCLC in vitro and in vivo. Cell viability was examined using the methyl-thiazol-diphenyl-tetrazolium (MTT) assay. Flow cytometry was applied to evaluate cell cycle distribution and apoptosis. The expression of proteins related to the cell cycle and apoptosis was analyzed by Western blot analysis. Additionally, an in vivo study was performed to determine the anti-SCLC effect on an H1688 subcutaneous tumor in a BALB/c nude mouse model. 11-Dehydrosinulariolide inhibited cell growth, triggered G2/M arrest and induced H1688 cell apoptosis in a dose- and time-dependent manner. Additionally, 11-dehydrosinulariolide caused the accumulation of p53 and Bax, accompanied by the activation of DNA damage-inducing kinases, including ataxia-telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2). Moreover, 11-dehydrosinulariolide increased the activity of caspase-3 and -7, suggesting that caspases are involved in 11-dehydrosinulariolide-induced apoptosis. 11-Dehydrosinulariolide also increased the level of tumor suppressor phosphatase and tensin homolog (PTEN) and inhibited the expression of phosphorylated Akt. In the in vivo study, the intraperitoneal injection of 11-dehydrosinulariolide at a dosage of 10 mg/kg significantly inhibited tumor growth compared with the control treatment. Together, the data indicate that 11-dehydrosinulariolide induces G (2)/M cell cycle arrest and apoptosis through various cellular processes, including the upregulation of p53 and Bax, activation of ATM and Chk2, activation of caspase-3 and -7, and accumulation of PTEN, leading to inhibition of the Akt pathway. These findings suggest that 11-dehydrosinulariolide might serve as a promising chemotherapy drug in the treatment of SCLC. Full article

A continuing chemical investigation of the ethyl acetate (EtOAc) extract of a reef soft coral Sinularia brassica, which was cultured in a tank, afforded four new steroids with methyl ester groups, sinubrasones A–D (1–4) for the first time. In particular, 1 possesses a β-D-xylopyranose. The structures of the new compounds were elucidated on the basis of spectroscopic analyses. The cytotoxicities of compounds 1–4 against the proliferation of a limited panel of cancer cell lines were assayed. The anti-inflammatory activities of these new compounds 1–4 were also evaluated by measuring their ability to suppress superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced human neutrophils. Compounds 2 and 3 were shown to exhibit significant cytotoxicity, and compounds 3 and 4 were also found to display attracting anti-inflammatory activities. Full article