34176-52-8Relevant articles and documents
Novel thiazole–pyrazolone hybrids as potent ACE inhibitors and their cardioprotective effect on isoproterenol-induced myocardial infarction
You, Hongwen,Su, Xinyou,Su, Guoying
, (2020/08/27)
A facile synthesis of a group of novel thiazole–pyrazolone hybrids and their investigation for angiotensin-converting enzyme (ACE) inhibition are reported in this study. These compounds were synthesized using a well-known approach, based on the condensation of ethyl acetoacetate with thiazolylhydrazines, and characterized by various spectroscopic and analytical techniques. The entire set of compounds displayed a moderate-to-excellent inhibitory activity against ACE. In particular, compound 4i was found to be the most potent ACE inhibitor and was further studied for cardioprotective effects against isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Compound 4i improved the cardiac function and prevented cardiac injury induced by ISO in Sprague Dawley rats. The levels of oxidative stress and proinflammatory cytokines were also restored to near normal by 4i as compared with the ISO group. In the Western blot analysis, compound 4i prevented mitochondrial apoptosis after MI by downregulating the expression of cleaved caspase-3 and Bax, with the upregulation of Bcl-2, as compared with the ISO group.
Synthesis of some new 1,3,4-thiadiazole, thiazole and pyridine derivatives containing 1,2,3-triazole moiety
Abdelriheem, Nadia A.,Mohamed, Ali M. M.,Abdelhamid, Abdou O.
, (2017/02/26)
In this study, 1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethan-1-one, was reacted with Thiosemicarbazide, alkyl carbodithioate and benzaldehyde to give thiosemicarbazone, alkylidenehydrazinecarbodithioate and 3-phenylprop-2-en-1-one-1,2,3-triazole derivatives. The 1,3,4-thiadiazole derivatives containing the 1,2,3-triazole moiety were obtained via reaction of alkylidenecarbodithioate with hydrazonoyl halides. Also, hydrazonoyl halides were reacted with thiosemicarbazone and pyrazolylthioamide to give 1,3-thiazoles derivatives. Subsequently, 3-phenyl-2-en-1-one was used to synthesize substituted pyridines and substituted nicotinic acid ester. The latter was converted to its azide compound which was reacted with aromatic amines and phenol to give substituted urea and phenylcarbamate containing 1,2,3-triazole moiety. The newly synthesized compounds were established by elemental analysis, spectral data and alternative synthesis whenever possible.
Structure-based design of potent human dihydroorotate dehydrogenase inhibitors as anticancer agents
Song, Wenlin,Li, Shiliang,Tong, Yi,Wang, Jiawei,Quan, Lina,Chen, Zhuo,Zhao, Zhenjiang,Xu, Yufang,Zhu, Lili,Qian, Xuhong,Li, Honglin
, p. 1441 - 1448 (2016/07/21)
It has been proven that inhibiting human dihydroorotate dehydrogenase (hDHODH) restricts the growth of rapidly proliferating cells, thus hDHODH can be developed as a promising target for the treatment of immunological disease and cancer. Here, a succession of substituted hydrazino-thiazole derivatives were designed, synthesized, and biologically evaluated through structure-based optimization, of which compound 22 was the most potent inhibitor of hDHODH with an IC50 value of 1.8 nM. Furthermore, 22 exhibited much better antiproliferative activity than brequinar, both in HCT-116 and BxPC-3 cancer cell lines. Flow cytometry analysis revealed that 22 induced S phase cell cycle arrest and promoted induction of apoptosis. All results established a proof that blocking the pyrimidine de novo synthesis pathway by inhibiting the rate-limiting enzyme hDHODH is an attractive therapy for cancer.
