Bonde Chandrakant G, Gaikwad Naresh J
Department of Pharmaceutical Sciences, Nagpur University Campus, Nagpur University, Amravati Road, Nagpur 440033, India.
Bioorg Med Chem. 2004 May 1;12(9):2151-61. doi: 10.1016/j.bmc.2004.02.024.
A series of N'-[3,4-disubstituted-1,3-thiazol-2(3H)-ylidene]-2-(pyrazin-2-yloxy)acetohydrazide 11-66 and N'-[(2Z)-3-(4-bromophenyl)-4-oxo-1,3-thiazolidin-2-ylidene]-2-(pyrazin-2-yloxy)acetohydrazide 68-74 were synthesized using appropriate synthetic route. The entire test compounds 11-66 and 68-74 were assayed in vitro for antibacterial activity against two different strains of Gram-negative (E. coli and S. typhi), Gram-positive (S. aureus and B. subtilis) bacteria and the antimycobacterial activity was evaluated against H(37)Rv strain of Mycobacterium tuberculosis. The minimum inhibitory concentration (MIC) was determined for test compounds and for reference standards. The test compounds showed significant antibacterial and antimycobacterial activity against the microbial strains used, when tested in vitro. In general, pyrazine ring and substituted thiazoline ring are essential for antimicrobial activity. Among the compounds tested, compounds 11, 12 and 40 were found to be most potent. The toxicity of most potent compounds 11, 12 and 40 were determined using hemolytic assay and minimal hemolytic concentration (MHCs) were determined. The test compounds were found to be nontoxic up to a dose level of 250 microg/mL.
采用适当的合成路线合成了一系列N'-[3,4-二取代-1,3-噻唑-2(3H)-亚基]-2-(吡嗪-2-基氧基)乙酰肼11 - 66和N'-[(2Z)-3-(4-溴苯基)-4-氧代-1,3-噻唑烷-2-亚基]-2-(吡嗪-2-基氧基)乙酰肼68 - 74。对所有测试化合物11 - 66和68 - 74进行了体外抗菌活性测定，针对两种不同的革兰氏阴性菌（大肠杆菌和伤寒沙门氏菌）、革兰氏阳性菌（金黄色葡萄球菌和枯草芽孢杆菌），并评估了对结核分枝杆菌H(37)Rv菌株的抗分枝杆菌活性。测定了测试化合物和参考标准品的最低抑菌浓度（MIC）。测试化合物在体外测试时，对所用的微生物菌株显示出显著的抗菌和抗分枝杆菌活性。一般来说，吡嗪环和取代的噻唑啉环对抗菌活性至关重要。在所测试的化合物中，发现化合物11、12和40最为有效。使用溶血试验测定了最有效化合物11、12和40的毒性，并确定了最小溶血浓度（MHCs）。发现测试化合物在剂量水平达到250μg/mL时无毒。
