Anti-proliferation activity of synthetic ajoene analogues on cancer cell-lines.
The ability of garlic preparations to inhibit cancer cell-growth has been attributed to a group of structurally-related organosulfur compounds found in the crushed clove. Historically, interest has centred on three such compounds as allicin, diallyl disulfide and diallyl trisulfide, with less interest on E- and Z-ajoene. A recently developed synthetic route from our laboratory for preparing ajoene analogues allows access to derivatives containing the sulfoxide / vinyl disulfide core whilst varying the terminal end-group functionality. A small library has been synthesized and an advanced lead with p-methoxybenzyl end groups (8) identified. Data on the in vitro anti-proliferation activity of compound (8) is presented here against six cancer cell-lines in comparison with that of Z- and E-ajoene to reveal an enhancement in activity of up to twelvefold. In addition, a modest selectivity is observed for tumour over normal cell-lines of up to threefold. Data on ajoene and its derivatives is presented in the context of chemosensitization in drug-resistance, and ideas on ajoene's mode of action at the molecular level are presented and discussed.
International Centre for Genetic Engineering and Biotechnology, UCT Medical School, South Africa.
Catherine H
CH
Kaschula
Roger
R
Hunter
Hassan T
HT
Hassan
Nashia
N
Stellenboom
Jonathan
J
Cotton
Xiao Q
XQ
Zhai
M Iqbal
MI
Parker
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004220:Disulfides / Q000138:chemical synthesis / Q000494:pharmacology*; D005260:Female; D005737:Garlic / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013454:Sulfoxides
D000970:Antineoplastic Agents; D004220:Disulfides; D054852:Small Molecule Libraries; D013454:Sulfoxides; C048980:ajoene