Metabolites of endophytic fungi in Croton sublyratus Kurz. leaves

Abstract

The purpose of this research was to isolate metabolites of endophytic fungus isolate Bkk3 obtained from Croton sublyratus Kurz. leaves. Based on nucleotide sequences of ITS1-5.8S-ITS2 regions of rDNA, the fungus isolate Bkk3 was identified as Diaporthe sp. The dichloromethane extract of malt extract broth of the fungus Bkk3 was purified by chromatographic techniques to afford a novel compound named diaporthichalasin together with two known compounds, pycnidione and 5-methymellein. Their structures were elucidated by analysis of UV, IR, MS, and NMR. The structure of diaporthichalasin was confirmed by single crystal X-ray crystallographic analysis. Diaporthichalasin exhibits significantly potent inhibition of CYP3A4 with and IC[subscript50] value of 0.626 micrometer and shows cytotoxic activity against BT474 (breast), CHAGO (lung), HEP-G2 (hepatoma), KATO-3 (gastric) and SW620 (colon) with the IC[subscript50) values of 18.01, 13.94, 11.29, 9.86 and 0.93 micrometer, respectively while pycnidione inhibits CYP3A4 with the IC[subscript50] value of 465 micrometer and displays cytotoxic activity against BT474(breast), CHAGO (lung), HEP-G2 (hepatoma), KATO-3(gastric) and SW620(colon) with the IC[subscript50] values of 18.25, 1.28, 11.72, 1.37 and 12.92 micrometer, respectively. However all of three compound do not show antimicrobial activity against B. subtilis ATCC 6633, S aureus ATCC 25923, E coli AtCC 25922, P. aeruginosa ATTC 27853 and C.albicans STCC 10231