Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 17, Issue 22, Pages 7816-7822Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2009.09.011
Keywords
Oxadiazole; Thiadiazole; Phosphodiesterase 1; Snake venom; Nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1)
Funding
- Fatmid Foundation
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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 V-max values decreases without affecting the K-m 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 mu M, respectively. The K-i values were 100 mu M and 360 mu M against the snake venom and human recombinant NPP1 enzyme, respectively. Most active compounds were found to be non-toxic in neutrophil viability assay. (C) 2009 Elsevier Ltd. All rights reserved.
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