Asunto(s)
Allium/química , Neoplasias/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Compuestos de Azufre/uso terapéutico , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Compuestos de Azufre/química , Compuestos de Azufre/farmacologíaRESUMEN
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.