1,3,4-Oxadiazole-2(3H)-thione and its analogues: A new class of non-competitive nucleotide pyrophosphatases/phosphodiesterases 1 inhibitors |
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Authors: | Khalid M Khan Naheed Fatima Maimona Rasheed Saima Jalil Nida Ambreen Shahnaz Perveen M Iqbal Choudhary |
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Institution: | 1. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan;2. PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi-75280, Pakistan |
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Abstract: | A series of 1,3,4-oxadiazole-2 (3H)-thiones and 1,3,4-thiadiazole-2 (3H)-thiones were synthesized and evaluated for their inhibitory activities against the two nucleotide pyrophosphatase phosphodiesterase 1 enzymes. Dixon, as well as Lineweaver–Burk plots, and their secondary replots have indicated that the inhibition was of pure non-competitive type, against both snake venom and pure human recombinant enzymes as the Vmax values decreases without affecting the Km values. 5-4-(t-Butyldimethylsilyloxy)-phenyl]-1,3,4-thiadiazole-2 (3H)-thione (17) and 4-(t-butyldimethylsilyloxy)-phenyl]-1,3,4-oxadiazole-2 (3H)-thione (1) were found to be the most active compounds with IC50 values 66.47 and 368 μM, respectively. The Ki values were 100 μM and 360 μM against the snake venom and human recombinant NPP1 enzyme, respectively. Most active compounds were found to be non-toxic in neutrophil viability assay. |
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