Department of Chemistry, D.D.U. Gorakhpur University, Gorakhpur-273009, UP, India.
Department of Physics, D.D.U. Gorakhpur University, Gorakhpur-273009, UP, India.
Bioorg Chem. 2021 Mar;108:104611. doi: 10.1016/j.bioorg.2020.104611. Epub 2021 Jan 5.
In the present study, a series of novel quinazolinone hybrids, viz. triazepino-quinazolinones 4, thiazolo-triazolo-quinazolinones 7 and triazolo-quinazolinones 8 have been synthesized from the key intermediate 3-(substituted phenyl)-2-hydrazinoquinazolin-4(3H)-ones 3. All the newly synthesized compounds were characterized by means of spectral (IR, H NMR, C NMR) and elemental analysis. The target compounds were biologically screened for their in vitro antimicrobial and antitubercular activities against pathogenic strain. The results of bioassay demonstrated that some of the compounds exhibited pronounced antimicrobial activity comparable to that of standard drugs tested under similar conditions. Compounds 4c, 4e, 7e and 8b showed relatively very good inhibitory activity against pathogenic bacteria with minimum inhibitory concentration (MIC) of 2.6 μg/mL, 5.2 μg/mL, while the rest of the compounds showed moderate activity. Compounds 4c and 8b were found to be nearly equipotent with ciprofloxacin against P. aeruginosa with MIC 5.2 μg/mL, while compound 8b was more potent against pathogenic bacteria S. aureus. It is very remarkable that four compounds, 4c, 4e, 7e and 8b showed pronounced antifungal activity against selected pathogenic fungi, A. niger, C. albicans with MIC 2.6 μg/mL and 5.2 μg/mL. The antitubercular activity of synthesized compounds reveal that compound 8b showed better activity than the other compounds with a MIC of 5.2 μg/mL against M. tuberculosis (HRv). Molecular docking studies of the compounds were performed to rationalize the inhibitory properties of these compounds and results showed that these compounds have good binding energy and better binding affinity within the active pocket, thus these compounds may be considered as potent inhibitors towards selective targets.
在本研究中，我们从关键中间体 3-(取代苯基)-2-肼基喹唑啉-4(3H)-酮 3 合成了一系列新型喹唑啉酮杂合体，即三唑并[1,5-a]嘧啶并喹唑啉酮 4、噻唑并三唑并喹唑啉酮 7 和三唑并喹唑啉酮 8。所有新合成的化合物均通过光谱（IR、H NMR、C NMR）和元素分析进行了表征。目标化合物进行了体外抗微生物和抗结核活性的生物筛选，以评估其对致病菌株的作用。生物测定结果表明，一些化合物表现出与标准药物相当的显著抗微生物活性。化合物 4c、4e、7e 和 8b 对致病菌具有相对非常好的抑制活性，最低抑菌浓度（MIC）为 2.6 μg/mL、5.2 μg/mL，而其余化合物表现出中等活性。化合物 4c 和 8b 对铜绿假单胞菌的活性与环丙沙星相当，MIC 为 5.2 μg/mL，而化合物 8b 对金黄色葡萄球菌的活性更强。非常值得注意的是，有四种化合物，即 4c、4e、7e 和 8b 对所选致病真菌黑曲霉和白色念珠菌表现出明显的抗真菌活性，MIC 为 2.6 μg/mL 和 5.2 μg/mL。合成化合物的抗结核活性表明，化合物 8b 对结核分枝杆菌（HRv）的活性优于其他化合物，MIC 为 5.2 μg/mL。对这些化合物进行了分子对接研究，以合理化这些化合物的抑制特性，结果表明这些化合物在活性口袋内具有良好的结合能和更好的结合亲和力，因此这些化合物可能被认为是针对选择性靶标的有效抑制剂。
