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

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.

Bioactive cyclobutane-containing alkaloids

“…b-Lumicolchicine, (-)-colchicine, and (-)-cornigerine were isolated from Jordanian Colchicum species: C. hierosolymitanum and C. tunicatum (Colchicaceae) [149], C. stevenii [150], and C. brachyphyllum [151]. All pure compounds were evaluated for cytotoxicity against three human cancer cell lines: MCF-7 human breast carcinoma, NCI-H460 human large cell lung carcinoma, and SF-268 human astrocytoma.…”

Proliferation of Antibiotic-Producing Bacteria and Concomitant Antibiotic Production as the Basis for the Antibiotic Activity of Jordan's Red Soils

“…The organic fraction (lower portion) was removed and dried in vacuo. A measured aliquot of this fraction was dissolved in 1 ml of DMSO, and the antimicrobial activity was measured as described previously (5).…”

Dendrimer-Encapsulated Camptothecins: Increased Solubility, Cellular Uptake, and Cellular Retention Affords Enhanced Anticancer Activity In vitro

“…The cytotoxicity of 10HCPT, BACPT, and their corresponding dendrimer encapsulation formulations were evaluated in a human cancer cell panel using a procedure described previously (46). MCF-7 human breast carcinoma (Barbara A. Karmanos Cancer Center, Detroit, MI), NCI-H460 human large cell lung carcinoma (American Type Culture Collection, Manassas, VA), and SF-268 human astrocytoma (NCI Developmental Therapeutics Program, Frederick, MD) cell lines were all adapted and maintained in RPMI 1640 supplemented with fetal bovine serum (Life Technologies/Invitrogen, Carlsbad, CA) at 10% (v/v) and the antibiotics, penicillin G (100 units/mL) and streptomycin sulfate (100 Ag/mL), in a humidified 5% CO 2 atmosphere kept at 37jC.…”