Seven new phenylspirodrimanes, named stachybotrins D-F (1, 3, 4), stachybocins E and F (5, 6), and stachybosides A and B (7, 8), and four known compounds (2, 9-11), were isolated from the sponge-derived fungus Stachybotrys chartarum MXH-X73. Their structures were determined by detailed analysis of spectroscopic data. The absolute configurations of 1-8 were determined by chemical hydrolysis and modified Mosher's and Marfey's methods. All compounds were tested in an anti-HIV activity assay, and compound 1 showed an inhibitory effect on HIV-1 replication by targeting reverse transcriptase. Further study exhibited that 1 could block NNRTIs-resistant strains (HIV-1RT-K103N, HIV-1RT-L100I,K103N, HIV-1RT-K103N,V108I, HIV-1RT-K103N,G190A, and HIV-1RT-K103N,P225H) as well as wild-type HIV-1 (HIV-1wt) with EC50 values of 7.0, 23.8, 13.3, 14.2, 6.2, and 8.4 μM, respectively.
anti-HIV activity, phenylspirodrimanes, Stachybotrys chartarum, reverse transcriptase
NCBI PubMed ID: 24308675Publication DOI: 10.1021/np400683hJournal NLM ID: 7906882Publisher: American Society of Pharmacognosy
Correspondence: Guo Y
; Li D
Institutions: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Methods: 13C NMR, 1H NMR, methylation, IR, DNA techniques, ESI-MS, acid hydrolysis, biological assays, HPLC, UV, extraction, optical rotation measurement, chromium trioxide oxidation, CC, cell growth, HR-ESI-MS, cytotoxicity assay, derivatization, evaporation, filtration
Found