Substituted ajoenes as novel anti-cancer agents.
A new synthesis of the ajoene pharmacophore core is presented involving the regioselective radical addition of a thiyl radical to a terminal alkyne as the key step. The synthesis allows structural variation of the two end groups on sulfur, and a range of novel derivatives varying the R(1) group (sulfoxide end) has been prepared and tested against CT-1 transformed fibroblast cells for anti-cancer activity. The results indicate comparable or even improved activity compared to the parent natural product ajoene isomers. This opens up the way to systematically studying the biology of the ajoene core.
Hunter
Roger
R
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa. Roger.Hunter@uct.ac.za
Kaschula
Catherine H
CH
Parker
Iqbal M
IM
Caira
Mino R
MR
Richards
Philip
P
Travis
Susan
S
Taute
Francois
F
Qwebani
Thozama
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D020650:Combinatorial Chemistry Techniques; D003561:Cytarabine / Q000494:pharmacology; D004220:Disulfides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005737:Garlic / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013454:Sulfoxides; D014327:Trophoblasts / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D004220:Disulfides; D013454:Sulfoxides; D003561:Cytarabine; C048980:ajoene