Quinone reductase 1 (QR1) is a cytoprotective enzymes that exerts its cancer chemoprective activity in two different ways. First, it suppresses formation of intracellular semiquinone radicals. Second, it generates intracellular free radical scavengers such as a-tocopherolhydroquinone. Therefore, it has been proposed that QR1 inducers may act as cancer chemopreventive agents. 3,5-Diphenyl-1,2,4-thiadiazole provided a new scaffold for novel QR1 inducers. This new scaffold was derived from the natural product resveratrol by replacement of the ethylene linker with five-membered heterocycle. 3,5-Bis(2-fluorophenyl)-1,2,4-thiadiazole has been obtained with a notable improvement in the QR1 induction activity (CD = 1.8 mM) in comparison with resveratrol (CD = 21 mM), where CD is the concentration to double the QR1 activity. Using thiazole as a linker and optimizing the subsitiuent pattern of the two phenyl rings led to a highly potent and selective QR1 inducer with a CD value of 87 nM.

Optimization of thiazole analogs of resveratrol for induction of quinone reductase 1 (QR1)

243rd National Meeting (2012)

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