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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
chemistry
Structure-activity studies on the anti-proliferation activity of ajoene analogues in WHCO1 oesophageal cancer cells
European Journal of Medicinal Chemistry, Volume 50, Year 2012
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Description
The organosulfur compound ajoene derived from the rearrangement of allicin found in crushed garlic can inhibit the proliferation of tumour cells by inducing G 2/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 IC 50 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. © 2012 Elsevier Masson SAS. All rights reserved.
Authors & Co-Authors
Kaschula, Catherine H.
South Africa, Cape Town
University of Cape Town
Italy, Trieste
International Centre for Genetic Engineering and Biotechnology
Hunter, Roger
South Africa, Cape Town
University of Cape Town
Stellenboom, Nashia
South Africa, Cape Town
University of Cape Town
Caira, Mino R.
South Africa, Cape Town
University of Cape Town
Winks, Susan
South Africa, Cape Town
University of Cape Town
Ogunleye, Thozama
South Africa, Cape Town
University of Cape Town
Richards, Philip
South Africa, Cape Town
University of Cape Town
Cotton, Jonathan
South Africa, Cape Town
University of Cape Town
Zilbeyaz, Kani
South Africa, Cape Town
University of Cape Town
Turkey, Agri
Aǧrı İbrahim Çeçen Üniversitesi
Wang, Yabing
South Africa, Cape Town
University of Cape Town
Italy, Trieste
International Centre for Genetic Engineering and Biotechnology
Siyo, Vuyolwethu
South Africa, Cape Town
University of Cape Town
Italy, Trieste
International Centre for Genetic Engineering and Biotechnology
Ngarande, Ellen
South Africa, Cape Town
University of Cape Town
Italy, Trieste
International Centre for Genetic Engineering and Biotechnology
Parker, M. Iqbal
South Africa, Cape Town
University of Cape Town
Italy, Trieste
International Centre for Genetic Engineering and Biotechnology
Statistics
Citations: 53
Authors: 13
Affiliations: 3
Identifiers
Doi:
10.1016/j.ejmech.2012.01.058
ISSN:
02235234
e-ISSN:
17683254
Research Areas
Cancer
Health System And Policy