Mehta Dinesh K, Taya Poonam, Das Rina, Dua Kamal
M.M. College of Pharmacy, Department of Pharmaceutical Chemistry, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, HR-133207, India.
R.K.S.D College of Pharmacy, Ambala Road, Kaithal, Haryana-136027, India.
Antiinflamm Antiallergy Agents Med Chem. 2019;18(2):91-109. doi: 10.2174/1871520619666190307162442.
Chemical modification of thiadiazole may lead to a potent therapeutic agent. In this study, biological properties of thiadiazole derivatives were evaluated by assessing their antimicrobial and anti-inflammatory activities.
A series of novel derivatives of N-(5-(1-methyl-indol-3-yl)-1,3,4-thiadiazol-2- yl)-2-(5-substitutedphenyl)-3-(phenylamino)-4,5-dihydropyrazol-1-yl) acetamide have been synthesized and evaluated for their antimicrobial activity. Anti-inflammatory activity was done using carrageenan-induced inflammation in rat paw edema model. In-silico molecular docking studies of the synthesized compounds were performed on crystal structures of Aspergillus niger, Bacillus subtilis, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Cyclooxygenase-2 (obtained from www.rcsb.org) using GRIP batch docking method of V-life MDS 3.0 software. The structures of the newly synthesized compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR and Mass spectroscopy.
Antimicrobial and Anti-inflammatory activity study of the novel synthesized compounds were screened. Synthesized compounds having methoxy substitution on the 3rd and 4th positions of aromatic ring are utmost active amongst all the derivatives. Compounds 6d, 6i, 6j and 6l were found to possess good anti-inflammatory activity having percentage of inhibition to the extent of 46.8%, 48.1%, 49.4%, and 48.5% as compared with Diclofenac.
The experimental results were further supported by molecular docking analysis describing the better interaction patterns.
噻二唑的化学修饰可能产生一种有效的治疗剂。在本研究中，通过评估噻二唑衍生物的抗菌和抗炎活性来评价其生物学特性。
合成了一系列新型的N-(5-(1-甲基-吲哚-3-基)-1,3,4-噻二唑-2-基)-2-(5-取代苯基)-3-(苯基氨基)-4,5-二氢吡唑-1-基)乙酰胺衍生物，并对其抗菌活性进行了评估。使用角叉菜胶诱导的大鼠足肿胀模型进行抗炎活性研究。使用V-life MDS 3.0软件的GRIP批量对接方法，对合成的化合物在黑曲霉、枯草芽孢杆菌、白色念珠菌、大肠杆菌、铜绿假单胞菌、金黄色葡萄球菌和环氧化酶-2（从www.rcsb.org获得）的晶体结构上进行了计算机辅助分子对接研究。通过傅里叶变换红外光谱、1H-核磁共振、13C-核磁共振和质谱对新合成化合物的结构进行了确证。
对新合成化合物的抗菌和抗炎活性进行了筛选。在所有衍生物中，芳环第3和第4位具有甲氧基取代的合成化合物活性最高。与双氯芬酸相比，发现化合物6d、6i、6j和6l具有良好的抗炎活性，抑制率分别为46.8%、48.1%、49.4%和48.5%。
分子对接分析描述了更好的相互作用模式，进一步支持了实验结果。
