New colchicinoids from a native Jordanian meadow saffron, colchicum brachyphyllum: isolation of the first naturally occurring dextrorotatory colchicinoid.
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.
Alali
Feras Q
FQ
Medicinal Chemistry and Pharmacognosy Department, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan. falali@just.edu.jo
El-Elimat
Tamam
T
Li
Chen
C
Qandil
Amjad
A
Alkofahi
Ahmad
A
Tawaha
Khaled
K
Burgess
Jason P
JP
Nakanishi
Yuka
Y
Kroll
David J
DJ
Navarro
Hernán A
HA
Falkinham
Joseph O
JO
Wani
Mansukh C
MC
Oberlies
Nicholas H
NH
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001156:Artemia / Q000187:drug effects; D045744:Cell Line, Tumor; D003078:Colchicine / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D003079:Colchicum / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007597:Jordan; D019906:Nuclear Magnetic Resonance, Biomolecular; D010946:Plants, Medicinal / Q000737:chemistry*; D013237:Stereoisomerism
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D003078:Colchicine