H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
Bioorg Med Chem. 2009 Nov 15;17(22):7816-22. doi: 10.1016/j.bmc.2009.09.011. Epub 2009 Sep 19.
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 IC(50) values 66.47 and 368microM, respectively. The K(i) values were 100microM and 360microM against the snake venom and human recombinant NPP1 enzyme, respectively. Most active compounds were found to be non-toxic in neutrophil viability assay.
合成了一系列 1,3,4-噁二唑-2(3H)-硫酮和 1,3,4-噻二唑-2(3H)-硫酮，并评估了它们对两种核苷酸焦磷酸酶磷酸二酯酶 1 酶的抑制活性。Dixon 以及 Lineweaver-Burk 图及其二次 replots 表明，抑制作用是纯非竞争性的，对蛇毒和纯人重组酶均如此，因为 V(max) 值降低而不影响 K(m) 值。5-[4-(叔丁基二甲基甲硅氧基)-苯基]-1,3,4-噻二唑-2(3H)-硫酮（17）和[4-(叔丁基二甲基甲硅氧基)-苯基]-1,3,4-噁二唑-2(3H)-硫酮（1）被发现是最具活性的化合物，IC(50) 值分别为 66.47 和 368μM。对蛇毒和人重组 NPP1 酶的 K(i) 值分别为 100μM 和 360μM。在中性粒细胞活力测定中，发现最具活性的化合物无毒性。
