Ilicicolin C suppresses the progression of prostate cancer by inhibiting PI3K/AKT/mTOR pathway.

Aberrant activation of the PI3K/AKT pathway is a driving factor in the development of prostate cancer. Therefore, inhibiting the function of the PI3K/AKT signaling pathway is a strategy for the treatment of prostate cancer. Ilicicolin C is an ascochlorin derivative isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501. Which has anti-inflammatory activity, but its activity against prostate cancer has not yet been elucidated. MTT assay, plate clone-formation assay, flow cytometry and real-time cell analysis technology were used to detect the effects of ilicicolin C on cell viability, proliferation, apoptosis and migration of prostate cancer cells. Molecular docking software and surface plasmon resonance technology were used to analyze the interaction between ilicicolin C and PI3K/AKT proteins. Western blot assay was performed to examine the changes in protein expression. Finally, QikProp software was used to simulate the process of ilicicolin C in vivo, and a zebrafish xenograft model was used to further verify the anti-prostate cancer activity of ilicicolin C in vivo. Ilicicolin C showed cytotoxic effects on prostate cancer cells, with the most significant effect on PC-3 cells. Ilicicolin C inhibited proliferation and migration of PC-3 cells. It could also block the cell cycle and induce apoptosis in PC-3 cells. In addition, ilicicolin C could bind to PI3K/AKT proteins. Furthermore, ilicicolin C inhibited the expression of PI3K, AKT and mTOR proteins and could also regulate the expression of downstream proteins in the PI3K/AKT/mTOR signaling pathway. Moreover, the calculations speculated that ilicicolin C was well absorbed orally, and the zebrafish xenograft model confirmed the in vivo anti-prostate cancer effect of ilicicolin C. Ilicicolin C emerges as a promising marine compound capable of inducing apoptosis of prostate cancer cells by counteracting the aberrant activation of PI3K/AKT/mTOR, suggesting that ilicicolin C may be a viable candidate for anti-prostate cancer drug development. These findings highlight the potential of ilicicolin C against prostate cancer and shed light on its mechanism of action.

Marine Natural Products from the Beibu Gulf: Sources, Chemistry, and Bioactivities.

Marine natural products (MNPs) play an important role in the discovery and development of new drugs. The Beibu Gulf of South China Sea harbors four representative marine ecosystems, including coral reefs, mangroves, seaweed beds, and coastal wetlands, which are rich in underexplored marine biological resources that produce a plethora of diversified MNPs. In our ongoing efforts to discover novel and biologically active MNPs from the Beibu Gulf, we provide a systematic overview of the sources, chemical structures, and bioactive properties of a total of 477 new MNPs derived from the Beibu Gulf, citing 133 references and covering the literature from the first report in November 2003 up to September 2022. These reviewed MNPs were structurally classified into polyketides (43%), terpenoids (40%), nitrogen-containing compounds (12%), and glucosides (5%), which mainly originated from microorganisms (52%) and macroorganisms (48%). Notably, they were predominantly found with cytotoxic, antibacterial, and anti-inflammatory activities. This review will shed light on these untapped Beibu Gulf-derived MNPs as promising lead compounds for the development of new drugs.

HPLC-DAD-Guided Isolation of Diversified Chaetoglobosins from the Coral-Associated Fungus Chaetomium globosum C2F17.

Cytochalasans have continuously aroused considerable attention among the chemistry and pharmacology communities due to their structural complexities and pharmacological significances. Sixteen structurally diverse chaetoglobosins, 10-(indol-3-yl)-[13]cytochalasans, including a new one, 6-O-methyl-chaetoglobosin Q (1), were isolated from the coral-associated fungus Chaetomium globosum C2F17. Their structures were accomplished by extensive spectroscopic analysis combined with single-crystal X-ray crystallography and ECD calculations. Meanwhile, the structures and absolute configurations of the previously reported compounds 6, 12, and 13 were confirmed by single-crystal X-ray analysis for the first time. Chaetoglobosins E (6) and Fex (11) showed significant cytotoxicity against a panel of cancer cell lines, K562, A549, Huh7, H1975, MCF-7, U937, BGC823, HL60, Hela, and MOLT-4, with the IC50 values ranging from 1.4 µM to 9.2 µM.

Recent Advances in Chemistry and Bioactivities of Secondary Metabolites from the Genus Acremonium.

Acremonium fungi is one of the greatest and most complex genera in Hyphomycetes, comprising 130 species of marine and terrestrial sources. The past decades have witnessed substantial chemical and biological investigations on the diverse secondary metabolites from the Acremonium species. To date, over 600 compounds with abundant chemical types as well as a wide range of bioactivities have been obtained from this genus, attracting considerable attention from chemists and pharmacologists. This review mainly summarizes the sources, chemical structures, and biological activities of 115 recently reported new compounds from the genus Acremonium from December 2016 to September 2023. They are structurally classified into terpenoids (42%), peptides (29%), polyketides (20%), and others (9%), among which marine sources are predominant (68%). Notably, these compounds were primarily screened with cytotoxic, antibacterial, and anti-inflammatory activities. This paper provides insights into the exploration and utilization of bioactive compounds in this genus, both within the scientific field and pharmaceutical industry.

An epipolythiodioxopiperazine alkaloid and diversified aromatic polyketides with cytotoxicity from the Beibu Gulf coral-derived fungus Emericella nidulans GXIMD 02509. / 北部湾珊瑚来源构巢裸胞壳菌GXIMD 02509ä¸­å ·æœ‰ç»†èƒžæ¯’æ€§çš„ä¸€ä¸ªå¤šç¡«ä»£äºŒé ®å“Œå—ªç”Ÿç‰©ç¢±å’Œç»“æž„å¤šæ ·çš„èŠ³é¦™èšé ®ç±»åŒ–åˆç‰©.

Marine microorganisms, especially marine fungi, have historically proven their value as a prolific source for structurally novel and pharmacologically active secondary metabolites (Deshmukh et al., 2018; Carroll et al., 2022). The corals constitute a dominant part of reefs with the highest biodiversity, and harbor highly diverse and abundant microbial symbionts in their tissue, skeleton, and mucus layer, with species-specific core members that are spatially partitioned across coral microhabitats (Wang WQ et al., 2022). The coral-associated fungi were very recently found to be vital producers of structurally diverse compounds, terpenes, alkaloids, peptides, aromatics, lactones, and steroids. They demonstrate a wide range of bioactivity such as anticancer, antimicrobial, and antifouling activity (Chen et al., 2022). The genetically powerful genus Emericella (Ascomycota), which has marine and terrestrial sources, includes over 30 species and is distributed worldwide. It is considered a rich source of diverse secondary metabolites with antimicrobial activity or cytotoxicity (Alburae et al., 2020). Notably, Emericella nidulans, the sexual state of a classic biosynthetic strain Aspergillus nidulans, was recently reported as an important source of highly methylated polyketides (Li et al., 2019) and isoindolone-containing meroterpenoids (Zhou et al., 2016) with unusual skeletons.

Anti-Vibrio potential of natural products from marine microorganisms.

The emergence of drug-resistant Vibrio poses a serious threat to aquaculture and human health, thus there is an urgent need for the discovery of new related antibiotics. Given that marine microorganisms (MMs) are evidenced as important sources of antibacterial natural products (NPs), great attention has been gained to the exploration of potential anti-Vibrio agents from MMs. This review summarizes the occurrence, structural diversity, and biological activities of 214 anti-Vibrio NPs isolated from MMs (from 1999 to July 2022), including 108 new compounds. They were predominantly originated from marine fungi (63%) and bacteria (30%) with great structural diversity, including polyketides, nitrogenous compounds, terpenoids, and steroids, among which polyketides account for nearly half (51%) of them. This review will shed light on the development of MMs derived NPs as potential anti-Vibrio lead compounds with promising applications in agriculture and human health.

Osteoclastogenesis inhibitory phenolic derivatives produced by the Beibu Gulf coral-associated fungus Acremonium sclerotigenum GXIMD 02501.

Three new chlorinated orsellinic aldehyde derivatives, orsaldechlorins A - C (1-3) and a naturally new brominated orsellinic acid (7), along with ten known biosynthetically related phenolic (4-6, 8-13) and cyclohexanone (14) derivatives, were identified from the Beibu Gulf coral-derived fungus Acremonium sclerotigenum GXIMD 02501. Their structures were determined by spectroscopic data interpretation and comparison with those reported in the literature. Several of them showed inhibition of lipopolysaccharide (LPS)-induced NF-κB activation in RAW 264.7 macrophages at 20 µM. Moreover, the two new potent inhibitors (1 and 2) suppressed RANKL-induced osteoclast differentiation without cytotoxicity in bone marrow macrophages cells (BMMs). Our findings reveal that the phenolic compounds could be potential candidates for the prevention and treatment of osteolytic bone diseases.

Exploring Marine-Derived Ascochlorins as Novel Human Dihydroorotate Dehydrogenase Inhibitors for Treatment of Triple-Negative Breast Cancer.

Human dihydroorotate dehydrogenase (hDHODH) is an attractive tumor target essential to de novo pyrimidine biosynthesis. Novel potent hDHODH inhibitors with low toxicity are urgently needed. Herein, we demonstrate the isolation of 25 ascochlorin (ASC) derivatives, including 13 new ones, from the coral-derived fungus Acremonium sclerotigenum, and several of them showed pronounced inhibitions against hDHODH and triple-negative breast cancer (TNBC) cell lines, MDA-MB-231/-468. Interestingly, we found that hDHODH is required for proliferation and survival of TNBC cells, and several ASCs significantly inhibited TNBC cell growth and induced their apoptosis via hDHODH inhibition. Furthermore, the novel and potent hDHODH inhibitors (1 and 21) efficiently suppressed tumor growth in patient-derived TNBC xenograft models without obvious body weight loss or overt toxicity in mice. Collectively, our findings offered a novel lead scaffold as the hDHODH inhibitor for further development of potent anticancer agents and a potential therapeutic strategy for TNBC.

Cytotoxic benzopyranone and xanthone derivatives from a coral symbiotic fungus Cladosporium halotolerans GXIMD 02502.

Coral-derived microorganisms have been historically proven to be prolific sources of bioactive secondary metabolites. Twelve benzopyranone and/or xanthone derivatives, including a new benzopyranone with an uncommon carboxyl group at C-8, coniochaetone K (1), were obtained from the Beibu Gulf-derived coral symbiotic fungus Cladosporium halotolerans GXIMD 02502. Their structures were determined by extensive spectroscopic data interpretation and comparison with literature values. The absolute configuration of 1 was accomplished by comparison of specific optical rotation as well as quantum chemical ECD calculations. The in vitro cytotoxicity of compounds 1-12 against two human prostatic cancer cell lines, C4-2B and 22RV1, were evaluated. And compounds 1, 3, 6-8, and 10-11 demonstrated significant cytotoxicity with inhibitions ranging from 55.8% to 82.1% at the concentration of 10 µM.