Ascomylactams A–C, Cytotoxic 12- or 13-Membered-Ring Macrocyclic Alkaloids Isolated from the Mangrove Endophytic Fungus Didymella sp. CYSK-4, and Structure Revisions of Phomapyrrolidones A and C

Abstract

Three new 12- or 13-membered-ring macrocyclic alkaloids, named ascomylactams A–C (1–3), along with the analogues phomapyrrolidone C (4) and phomapyrrolidone A (5) were isolated from the mangrove endophytic fungus Didymella sp. CYSK-4. Their structures were elucidated by analysis of extensive spectroscopic data and mass spectrometric data. The structures and absolute configurations of 1 and 2 were determined by single-crystal X-ray diffraction experiments, which represents the first crystal structures described for a (6/5/6/5) tetracyclic skeleton fused with a 12- or 13-membered-ring macrocyclic moiety. The configurations of phomapyrrolidone C (4) and phomapyrrolidone A (5) were revised by detailed analysis of the NMR data. In a cytotoxic assay, compounds 1 and 3 showed moderate cytotoxicity against MDA-MB-435, MDA-MB-231, SNB19, HCT116, NCI-H460, and PC-3 human cancer cell lines, with IC50 values in the range of 4.2–7.8 μM.

A Marine Alkaloid, Ascomylactam A, Suppresses Lung Tumorigenesis via Inducing Cell Cycle G1/S Arrest through ROS/Akt/Rb Pathway

“…AsA was prepared and purified from mangrove endophytic fungus Ascomycota sp. CYSK-4 as previously reported, and its structure was identified by interpretation of spectral data (MS, 1H NMR, 13C NMR, 2D NMR) and X-ray single crystal diffractive technique) [ 13 ]. The compound was dissolved in 99.9% dimethyl sulfoxide (DMSO) at a concentration of 10 mM as stock solution and diluted according to experimental requirements when used.…”

“…AsA, as a decahydrofluorene analogue with a tetracyclic skeleton fused with a 13-membered macrocyclic moiety, is relatively rare in the decahydrofluorene class. We recently demonstrated that AsA can effectively suppress the growth of cell lines derived from a variety of human tissues, including MDA-MB-435, HepG2, HCT116, and NCI-H460 [ 13 ]. In the present study, we found that AsA could inhibit the proliferation of lung cancer cells and suppress tumor cell growth in xenograft mouse models without obvious toxicity.…”

Cytochalasin H isolated from mangrove-derived endophytic fungus inhibits epithelial-mesenchymal transition and cancer stemness via YAP/TAZ signaling pathway in non-small cell lung cancer cells

“…Mangroves grow in the salt-tolerant ecosystems with high biodiversity, and the abundance and diversity of mangrove resources provide the great potential for the discovery of new compounds [22]. In recent years, multiple potential anticancer compounds have been found from mangrove-derived endophytic fungi [22][23][24][25]. In our previous study, we have isolated cytochalasin H (CyH) from endophytic fungus Phomopsis liquidambari derived from mangrove, which could induce apoptosis and inhibit migration and angiogenesis in NSCLC cells both in vitro and in vivo [26,27].…”

Antibiotics from Extremophilic Micromycetes

“…The systematic screening of marine microorganisms for the antibacterial activity revealed the strain of the Aspergillus genus [75], which produced sphingofungin I (239) and known polyketides including similar in structure sphingofungin D (240) [207]. Two new glycosilated alkylresorcins, resorcinosides A and |B (244,245), were isolated from the Penicillium janthinellum fungus [208]. Compounds 244 and 245 are the first representatives of the structural family of resorcinols, which are glycosylated at the alkyl, and not the aromatic, part of the molecule.…”

“…Three new macrocyclic alkaloids, ascomylactams А-С (308-310) were isolated from mangrove endophyte Didymella sp. CYSK-4 [244], along with the known analogs, phomapyrrolidones A and C (311, 312) [245], structure of which was refined. Two new stereoisomeric alkaloids, cladosporitins A (313) and B (314), were isolated from the culture fluid of the mangrove micromycete Cladosporium sp.…”