1372559-08-4Relevant academic research and scientific papers
Structure-activity studies on the anti-proliferation activity of ajoene analogues in WHCO1 oesophageal cancer cells
Kaschula, Catherine H.,Hunter, Roger,Stellenboom, Nashia,Caira, Mino R.,Winks, Susan,Ogunleye, Thozama,Richards, Philip,Cotton, Jonathan,Zilbeyaz, Kani,Wang, Yabing,Siyo, Vuyolwethu,Ngarande, Ellen,Parker, M. Iqbal
, p. 236 - 254 (2012)
The organosulfur compound ajoene derived from the rearrangement of allicin found in crushed garlic can inhibit the proliferation of tumour cells by inducing G2/M cell cycle arrest and apoptosis. We report on the application of a concise four-step synthesis (Hunter et al., 2008 [1]) that allows access to ajoene analogues with the end allyl groups substituted. A library of twelve such derivatives tested for their anti-proliferation activity against WHCO1 oesophageal cancer cells has identified a derivative containing p-methoxybenzyl (PMB)-substituted end groups that is twelve times more active than Z-ajoene, with an IC50 of 2.1 μM (Kaschula et al., 2011 [2]). Structure-activity studies involving modification of the sulfoxide and vinyl disulfide groups of this lead have revealed that the disulfide is the ajoene pharmacophore responsible for inhibiting WHCO1 cell growth, inducing G 2/M cell cycle arrest and apoptosis by caspase-3 activation, and that the vinyl group serves to enhance the anti-proliferation activity a further eightfold. Reaction of the lead with cysteine in refluxing THF as a model reaction for ajoene's mechanism of action based on a thiol/disulfide exchange reveals that the allylic sulfur of the vinyl disulfide is the site of thiol attack in the exchange.
