Anti-Proliferative Activity of Synthetic Ajoene Analogues on Cancer Cell-Lines

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 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.

Garlic (Allium sativum) Stimulates Lipopolysaccharide‐induced Tumor Necrosis Factor‐alpha Production from J774A.1 Murine Macrophages

“…Garlic has been used as a home remedy for a myriad of diseases for thousands of years. To date, garlic and its constituents are known to have many beneficial attributes such as antimicrobial (Casella et al, 2013;Goncagul and Ayaz, 2010), antiatherosclerotic (Asdaq et al, 2009;Chan et al, 2013;Gonen et al, 2005;Malekpour-Dehkordi et al, 2013), antitumorigenetic (Iciek et al, 2009;Kaschula et al, 2011), and immunomodulatory (Iciek et al, 2009) properties. Of particular interest for our studies is the modulation of cytokine production by garlic as cytokines are important immune system mediators.…”

Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras

“…Thus far the best characterized naturally occurring H 2 S-donating compound from garlic ( Allium sativum ) is allicin (diallyl thiosulfinate) which decomposes in water to a number of compounds [56]. Benavides et al [57] measured H 2 S production in real time with a polarographic sensor and observed that under anoxic conditions and in the presence of GSH, red blood cells rapidly (within minutes) produced H 2 S from garlic extract as well as from two of the decomposition products of allicin, diallyl disulfide (DADS) and diallyl trisulfide (DATS; Fig, 2A), with approximately 3 times the yield from the latter.…”

The Natural Killer Cell: A Historical Perspective and the Use of Supplements to Enhance NKC Activity

“…Garlic reduces the side effects caused by anti-cancer agents. Thus, garlic and garlic-derived compounds are promising candidates for breast cancer cont ility of garlic preparations to inhibit cancer cell-growth has been attributed to a group of structurally-related organosulfur compounds found in the crushed clove [103]. For many years, in vitro and in vivo studies have reported that organosulfur compounds (OSCs), naturally found in Allium vegetables are able to suppress the proliferation of various tumor cells.…”