Affiliation:
1. Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China
2. Guangxi Key Laboratory of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China
3. Guangxi Scientific Research Center of Traditional Chinese Medicine, Nanning 530200, China
Abstract
Mangrove-derived actinomycetes represent a rich source of novel bioactive natural products in drug discovery. In this study, four new polyene macrolide antibiotics antifungalmycin B-E (1–4), along with seven known analogs (5–11), were isolated from the fermentation broth of the mangrove strain Streptomyces hiroshimensis GXIMD 06359. All compounds from this strain were purified using semi-preparative HPLC and Sephadex LH-20 gel filtration while following an antifungal activity-guided fractionation. Their structures were elucidated through spectroscopic techniques including UV, HR-ESI-MS, and NMR. These compounds exhibited broad-spectrum antifungal activity against Talaromyces marneffei with minimum inhibitory concentration (MIC) values being in the range of 2–128 μg/mL except compound 2. This is the first report of polyene derivatives produced by S. hiroshimensis as bioactive compounds against T. marneffei. In vitro studies showed that compound 1 exerted a significantly stronger antifungal activity against T. marneffei than other new compounds, and the antifungal mechanism of compound 1 may be related to the disrupted cell membrane, which causes mitochondrial dysfunction, resulting in leakage of intracellular biological components, and subsequently, cell death. Taken together, this study provides a basis for compound 1 preventing and controlling talaromycosis.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Guangxi
National Natural Science Foundation
Special Fund for Bagui Scholars of Guangxi (Yonghong Liu), Guangxi University of Chinese Medicine “Guipai Traditional Chinese Medicine Inheritance and Innovation Team” Project
High-level Talent of Guangxi Traditional Chinese Medicine
scientific Research Foundation of Institute of Marine Drugs, GXUCM
Subject
Drug Discovery,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Pharmaceutical Science