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ID: ALA1667735

Journal: J Nat Prod

Title: Human cytochrome P450 liability studies of trans-dihydronarciclasine: a readily available, potent, and selective cancer cell growth inhibitor.

Authors: McNulty J, Thorat A, Vurgun N, Nair JJ, Makaji E, Crankshaw DJ, Holloway AC, Pandey S.

Abstract: The cytochrome P45O activities of the naturally occurring Amaryllidaceae alkaloid narciclasine (3), isolated from Narcissus pseudonarcissus, and synthetic derivative trans-dihydronarciclasine (5) are reported. While narciclasine was found to possess potent inhibitory activity to human CYP3A4, its dihydro analogue was inactive. This study revealed that the C1-C10b double bond is required for inhibition of this crucial metabolizing enzyme. Compound 5 also demonstrated no inhibition of the related human cytochromes CYP19 and CYP1A1. This study elevates the status of trans-dihydronarciclasine (5) as a highly privileged, readily available molecule, with potent and selective anticancer activity.

CiteXplore: 21105682

DOI: 10.1021/np100657w