Department of Chemistry, New Horizon College of Engineering, Bangalore 560 103, India.
Department of Chemistry, Malnad College of Engineering, Hassan 573 202, India.
ACS Comb Sci. 2020 Oct 12;22(10):509-518. doi: 10.1021/acscombsci.0c00038. Epub 2020 Aug 18.
A MoS2-supported-calix[4]arene (MoS2-CA4) nanocatalyst was used for efficient synthesis of 2,4,5-trisubstituted imidazole derivatives from 1-(4-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)ethane-1,2-dione, aldehydes and ammonium acetate under solvent-free conditions. Reusability of the catalyst up to five cycles without any significant loss in the yields of the product is the unique feature of this heterogeneous solid catalysis. Furthermore, the noteworthy highlights of this method are safe reaction profiles, broad substrate scope, excellent yields, economical, solvent-free, and simple workup conditions. All synthesized compounds were evaluated for their in vitro antitubercular (TB) activity against (Mtb) H37Rv. Among the screened compounds 3c, 3d, 3f, 3m, and 3r had MIC values of 2.15, 2.78, 5.75, 1.36, and 0.75 μM, respectively, and exhibited more potency than the reference drugs pyrazinamide (MIC: 3.12 μM), ciprofloxacin (MIC: 4.73 μM), and ethambutol (7.61 μM). Besides, potent compounds (3c, 3d, 3f, 3m, and 3r) have been tested for inhibition of MabA (β-ketoacyl-ACP reductase) enzyme and cytotoxic activity against mammalian Vero cell line. A molecular docking study was carried out on the MabA (PDB ID: 1UZN) enzyme to predict the interactions of the synthesized compounds. The results of the in vitro anti-TB activity and docking study showed that synthesized compounds have a strong anti-TB activity and can be adapted and produced more effectively as a lead compound.
一种 MoS2 负载杯[4]芳烃（MoS2-CA4）纳米催化剂被用于在无溶剂条件下，从 1-(4-硝基苯基)-2-(4-(三氟甲基)苯基)乙烷-1,2-二酮、醛和乙酸铵高效合成 2,4,5-三取代咪唑衍生物。该多相固体催化的独特之处在于催化剂可重复使用五轮，而产物产率没有明显损失。此外，该方法的显著特点是反应安全性高、底物适用范围广、产率高、经济实惠、无溶剂、以及操作简单。所有合成的化合物都进行了体外抗结核（TB）活性评估，针对 Mtb H37Rv。在所筛选的化合物中，3c、3d、3f、3m 和 3r 的 MIC 值分别为 2.15、2.78、5.75、1.36 和 0.75 μM，比对照药物吡嗪酰胺（MIC：3.12 μM）、环丙沙星（MIC：4.73 μM）和乙胺丁醇（7.61 μM）更有效。此外，还测试了有效化合物（3c、3d、3f、3m 和 3r）对 MabA（β-酮酰基-ACP 还原酶）酶的抑制作用以及对哺乳动物 Vero 细胞系的细胞毒性。对 MabA（PDB ID：1UZN）酶进行了分子对接研究，以预测合成化合物的相互作用。体外抗结核活性和对接研究结果表明，合成化合物具有很强的抗结核活性，可以作为先导化合物进行进一步开发和生产。
