Synthesis, in vitro antiurease, in vivo antinematodal activity of quinoline analogs and their in-silico study

Synthesis of quinoline analogs and their urease inhibitory activities with reference to the standard drug, thiourea (IC50 = 21.86 +/- 0.40 mu M) are presented in this study. The inhibitory activity range is (IC50 = 0.60 +/- 0.01 to 24.10 +/- 0.70 mu M) which displayed that it is most potent class of urease inhibitor. Analog 1-9, and 11-13 emerged with many times greater antiurease potential than thiourea, in which analog 1, 2, 3, 4, 8, 9, and 11 (IC50 = 3.50 +/- 0.10, 7.20 +/- 0.20, 1.30 +/- 0.10, 2.30 +/- 0.10, 0.60 +/- 0.01, 1.05 +/- 0.10 and 2.60 +/- 0.10 mu M respectively) were appeared the most potent ones among the series. In this context, most potent analogs such as 1, 3, 4, 8, and 9 were further subjected for their in vitro antinematodal study against C. elegans to examine its cytotoxicity under positive control of standard drug, Levamisole. Consequently, the cytotoxicity profile displayed that analogs 3, 8, and 9 were found with minimum cytotoxic outline at higher concentration (500 mu g/mL). All analogs were characterized through H-1 NMR, C-13 NMR and HR-EIMS. The protein-ligand binding interaction for most potent analogs was confirmed via molecular docking study.

Automated summary

This study synthesized quinoline analogs as urease inhibitors, which showed greater potency compared to the standard drug, thiourea. Some analogs were further tested for their cytotoxicity against C. elegans, with results showing minimal cytotoxic effects at higher concentrations. Protein-ligand binding interactions for the most potent analogs were confirmed through molecular docking study.