Shi-Hai Xu

Botryomeroterpenoids A (1) and B (2), two new andrastin-type meroterpenoids, along with two known analogues (3 and 4), were isolated from sponge-derived fungus Botryosporium sp. S5I2-1. Their structures were characterized by detailed spectroscopic analysis. Meanwhile, the absolute configurations of 1 and 2 were elucidated by comparing experimental and calculated ECD spectra. Compounds 1 and 2 were the first examples of andrastin-type meroterpenoids isolated from this genus, especially Compound 1 which represented the initial instance of 18-norandrastin-type meroterpenoids. Furthermore, the antibacterial activities of all compounds were also evaluated. However, the results indicated that these compounds showed no significant inhibitory activity against the tested bacteria with minimum inhibitory concentration (MIC) values of 32–64 μg/mL.

Four new methionine sulfoxide-containing diketopiperazines, (+)-dysidmetsulfoxide A [(+)-1], (+)-dysidmetsulfoxide B [(+)-2], (+)-dysidmetsulfoxide C [(+)-3] and (−)-dysidmetsulfoxide C [(−)-3], were isolated from the South China Sea sponge Dysidea sp. These compounds represented the first example of diketopiperazines possessing the unit of methionine sulfoxide (MetO) isolated from marine sponges. As it was difficult to determine the configuration of chiral sulfur atom in the thionyl group, the structures with absolute configurations of these compounds were elucidated by spectroscopic analyses and total synthesis. It was noteworthy that the purchased synthetic precursors, Fmoc-L- and Fmoc-D-MetO, were mixtures of epimers, respectively, due to the stereogenic sulfur atom in MetO, which were separated to prepare the optically pure isomers via the method of supercritical fluid chromatography (SFC). In addition, the other four optical isomers [(−)-1, (−)-2, (+)-4 and (−)-4] were also synthesized. Furthermore, (+)-1, (−)-1, (+)-3, (+)-4 and (−)-4 showed potential anti-Parkinson’s disease activities in an in vivo zebrafish model.

In recent years, marine natural products have continued to serve as a pivotal resource for novel drug discovery. Globally, the number of studies focusing on Porifera has been on the rise, underscoring their considerable importance and research value. Marine sponges are prolific producers of a vast array of bioactive compounds, including terpenes, alkaloids, peptides, and numerous secondary metabolites. Over the past fifteen years, a substantial number of sponge-derived terpenes have been identified, exhibiting extensive structural diversity and notable biological activities. These terpenes have been isolated from marine sponges or their associated symbiotic microorganisms, with several demonstrating multifaceted biological activities, such as anti-inflammatory, antibacterial, cytotoxic, anticancer, and antioxidant properties. In this review, we summarize 997 novel terpene metabolites, detailing their structures, sources, and activities, from January 2009 to December 2024. The structural features and structure-activity relationship (SAR) of different types of terpenes are broadly analyzed and summarized. This systematic and comprehensive review will contribute to the summary of and speculation on the taxonomy, activity profiles, and SAR of terpenes and the development of sponge-derived terpenes as potential lead drugs.

It is challenging to improve the effects of chemotherapy and reduce its adverse impact on the ovaries. Our previous study suggested that the combination of galaxamide could enhance the antitumor effect of cisplatin (CIS) in HeLa cell xenograft mice. However, their potential effects on ovarian tissues remain unknown. The Hela tumor-bearing female BALB/c mice model was established and randomly divided into three groups: control group (PBS group), CIS group (0.3 mg/kg CIS group) and galaxamide group (0.3 mg/kg CIS + 3 mg/kg galaxamide-treated group). The serum sex hormones levels, ovarian morphology, functional and molecular characterisation were determined and compared with those of the control group. The hormonal effects indicated premature ovarian insufficiency (POI) associated with CIS-induced tumor-bearing mice. CIS induces the apoptosis in primordial and developing follicles and subsequently increases follicular atresia, eventually leading to follicle loss. After cotreatment, galaxamide significantly increased anti-Mullerian hormone (AMH) and follicle-stimulating hormone receptor (FSHR) expression and prevented the CIS-induced PI3K pathway, which triggers follicle activation, apoptosis or atresia. These findings demonstrate that galaxamide could attenuate CIS-induced follicle loss by acting on the PI3K signaling pathway by stimulating AMH and/or FSHR and thus provides promising therapeutic options for patients with cervical cancer.

Four new cytochalasans, marchaetoglobins A-D (1-4), along with five known compounds (5-9), were isolated from the marine-sponge-associated fungus Chaetomium globosum 162105. Compounds 1-4 represent examples of 19,20-seco-chaetoglobosins, of which compound 1 is the first furan-containing cytochalasan. Their structures and absolute configurations were elucidated by extensive spectroscopic analyses and electronic circular dichroism calculations. Compounds 5, 8, and 9 displayed weak to moderate antibacterial activities against Bacillus thuringiensis, Edwardsiella piscicida, Vibrio alginolyticus, and Pseudomonas syringae pv. actinidiae with minimum inhibitory concentration values ranging from 5 to 25 μg/mL. In addition, compounds 2, 3, and 5 showed potent in vivo proangiogenic activity in transgenic zebrafish, comparable to the positive control.

A chemical investigation on the marine sponge Dysidea sp. resulted in the isolation of a series of diketopiperazines, including two new compounds, dysidines A (1) and B (2) as well as six known ones (3-8). Their structures with absolute configurations were determined on the basis of UV, IR, HRMS, NMR and calculated ECD method. Additionally, the cytotoxic, anti-inflammatory, antibacterial and antiviral activities of 1-8 were also tested. However, none of them exhibited significant bioactivities.

A new piperidone alkaloid, dysidone A (1), was isolated from the marine sponge Dysidea sp.

Our previous work reported that galaxamide, a cyclopeptide extracted from the seaweed Galaxaura filamentosa, showed antiproliferative activity against HeLa cells by MTT assay. In this study, the growth‐inhibitory effects of galaxamide in HeLa cells and xenograft mouse models were investigated. It was found galaxamide significantly inhibited cell growth, colony formation, migration, and invasion and induced cell apoptosis by inhibiting the Wnt signaling pathway in HeLa cells. RNA sequencing revealed that galaxamide regulated stemness by Wnt6 signaling pathway in HeLa cells. By analyzing The Cancer Genome Atlas database, Wnt6 was found to be negatively/positively correlated with stemness‐ and apoptosis‐related genes in human cervical cancer. Cancer stem‐like cells (CSCs) isolated and enriched from HeLa cells demonstrated elevated Wnt6 and β‐catenin genes compared with nonstem HeLa cells. After galaxamide treatment, CSCs showed abrogation of sphere‐forming ability, along with inhibition of stemness‐related and Wnt pathway genes. Galaxamide treatment was also accompanied by the induction of apoptosis in HeLa cells, which was consistent with the results in BALB/c nude mice. Our results provide evidence that suppression of stemness by downregulating the Wnt signaling pathway is the molecular mechanism by which galaxamide effectively inhibits cell growth and induces apoptosis in cervical cancer cells.

Two new alkaloids, spongimides A (1) and B (2), along with five known ones (3–7), were isolated from the marine sponge Spongia sp. The structures of 1 and 2 were determined by the spectroscopic methods (UV, IR, MS, and NMR) and X-ray diffraction analysis. Compounds 1, 3, and 4 were the first examples of 2,4-imidazolidinediones isolated from this genus. In addition, the cytotoxic and antibacterial activities of compounds 1 and 2 were also evaluated.