Fusarium proliferatum, an endophytic fungus from Dysoxylum binectariferum Hook.f, produces rohitukine, a chromane alkaloid possessing anti-cancer activity
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Rohitukine is a chromane alkaloid possessing anti-inflammatory, anti-cancer and immuno-modulatory properties. The compound was first reported from Amoora rohituka (Meliaceae) and later from Dysoxylum binectariferum (Meliaceae) and Schumanniophyton problematicum (Rubiaceae). Flavopiridol, a semi-synthetic derivative of rohitukine is a potent CDK inhibitor and is currently in Phase III clinical trials. In this study, the isolation of an endophytic fungus, Fusarium proliferatum (MTCC 9690) from the inner bark tissue of Dysoxylum binectariferum Hook.f (Meliaceae) is reported. The endophytic fungus produces rohitukine when cultured in shake flasks containing potato dextrose broth. The yield of rohitukine was 186 μg/100 g dry mycelial weight, substantially lower than that produced by the host tissue. The compound from the fungus was authenticated by comparing the LC–HRMS and LC–HRMS/MS spectra with those of the reference standard and that produced by the host plant. Methanolic extract of the fungus was cytotoxic against HCT-116 and MCF-7 human cancer cell lines (IC50 = 10 μg/ml for both cancer cell lines).
KeywordsDysoxylum binectariferum Endophytic fungus Fusarium proliferatum LC–HRMS/MS Rohitukine Flavopiridol
This work was supported in part by grants from the Department of Biotechnology, Government of India. Collection of samples and other field work was facilitated by the kind permission of the State Forest Department, Government of Karnataka. R. Uma Shaanker and B. T. Ramesha were supported partly by INFU, Technische Universität Dortmund during the preparation of the manuscript. Work was also supported by grants from the International Bureau (IB) of the German Federal Ministry of Education and Research (BMBF/DLR), Germany to M. Spiteller.
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