Jordan University of Science and Technology

New Colchicinoids from a Native Jordanian Meadow Saffron, Colchicum Brachyphyllum: Isolation of the First Naturally-Occurring Dextrorotatory Colchicinoid


Authors:  Feras Q. Alali, Tamam El-Elimat, Chen Li, Amjad Qandil, Ahmad Alkofahi, Khaled Tawaha, Jason P. Burgess, Yuka Nakanishi, David J. Kroll, Hernan A. Navarro, Joseph O. Falkinham, III, Mansukh C. Wani, and Nicholas H. Oberlies

Abstract:  
As part of our continuing investigation of Jordanian Colchicum species, the biologically active components of Colchicum brachyphyllum were pursued. Using bioactivity-directed fractionation, nine colchicinoids were isolated and characterized. One of these has a novel ring system, to which we have ascribed the trivial name (+)-demecolcinone (9), and it represents the first naturally occurring dextrorotatory colchicinoid. Another isolated compound was a new colchicinoid analogue, (-)-2,3-didemethyldemecolcine (8), while the remaining seven known colchicinoids were new to the species: (-)-colchicine (1), (-)-3-demethylcolchicine (2), (-)-cornigerine (3), beta-lumicolchicine (4), (-)-androbiphenyline (5), (-)-demecolcine (6), and (-)-3-demethyldemecolcine (7). The brine shrimp lethality test was used to direct the isolation of these colchicinoids. Moreover, all pure compounds were evaluated for cytotoxicity against a human cancer cell panel, for antimicrobial activity in an array of bacteria and fungi (including yeast), and for their potential to be allosteric modulators of the gamma-aminobutyric acid type A receptor.