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

Abstract

Synthesis of quinoline analogs and their urease inhibitory activities with reference to the standard drug, thiourea (IC₅₀ = 21.86 ± 0.40 µM) are presented in this study. The inhibitory activity range is (IC₅₀ = 0.60 ± 0.01 to 24.10 ± 0.70 µM) 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 µM 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 µg/mL). All analogs were characterized through ¹H NMR, ¹³C NMR and HR-EIMS. The protein-ligand binding interaction for most potent analogs was confirmed via molecular docking study.

Keywords: In vitro antiurease; In vivo antinematodal; Molecular docking; Quinolines; SAR; Synthesis.