Synthesis of gossypol atropisomers and derivatives and evaluation of their anti-proliferative and anti-oxidant activity

Gossypol 1, gossypolone 2, and a series of bis 3 and half Schiff’s bases 4 of gossypol were synthesised and tested for anti-proliferative and anti-oxidant activity. (−)-Gossypol (−)-1 was the most potent inhibitor of the proliferation of the HPV-16 keratinocyte cell line (using an MTT viability assay) with a GI50 of 4.8 μM. The bis Schiff’s base of (−)-gossypol with l-tyrosine ethyl ester (−)-3b was the most potent inhibitor of iron/ascorbate dependent lipid peroxidation (using the thiobarbituric acid test), with an IC50 of 11.7 μM, with (−)-gossypol being the next most potent of the series, with an IC50 of 13.1 μM. The results from these initial assays suggest that gossypol, as either a racemic mixture rac-1, or the individual atropisomers (−)-1 or (+)-1, has potential for the treatment of psoriasis.

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