Title: Anti-Proliferative Activity of Synthetic Ajoene Analogues on Cancer Cell-Lines
Volume: 11
Issue: 3
Author(s): Catherine H. Kaschula, Roger Hunter, Hassan T. Hassan, Nashia Stellenboom, Jonathan Cotton, Xiao Q. Zhai and M. Iqbal Parker
Affiliation:
Keywords:
Garlic, Ajoene, Anti-Cancer, Ajoene Analogues, Disulfide, sulfenyl substituent, E- and Z-isomeric forms, E/Z-mixtures, tumorogenic lymphoid cells (BJA-B), proliferation, fibroblasts, para-methoxybenzyl groups, peripheral mononuclear, blood cells, Anti-Cancer Drug
Abstract: 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 on 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 ajoenes mode of action at the molecular level are presented and discussed.
