In silico-guided proposition of potential nematocidal and antibacterial N-(1,3,4-thiadiazol-2-yl)benzamides

Abstract

A series of amide derivatives containing the 1,3,4-thiadiazole moiety has been recently synthesized and tested against Meloidogyne incognita (Kofold & White) Chitwood (nematode) and Xanthomonas oryzae pv. oryzae (Ishiyama) Swings, van den Mooter, Vauterin, Hoste, Gillis, Mew & Kersters (rice bacteria). We have now reported the quantitative structure-activity relationship (QSAR) modeling of these biological activities, as well as docking studies to understand the action mechanisms of these compounds. Novel agrochemical candidates were proposed based on an interplay of the substituents which most affect the biological data. The reliable and predictive models obtained from multivariate image analysis applied to QSAR (nematocidal: r2 = 0.750 and r2pred = 0.751; antibacterial: r2 = 0.650 and r2pred = 0.668) were employed to estimate the biological activities of the proposed compounds. At least two chemical candidates for each endpoint exhibited promising agrochemical performance, as the substituents R1 = CF3 or 2,4-diCl, R2 = CH2CH2Cl or CH2CH2Br, and X = SO2 demonstrated a synergistic effect on the nematocidal and antibacterial activities. The promising outcomes were supported by docking studies against the acetylcholinesterase (for M. incognita) and β-ketoacyl-acyl carrier protein synthase (for Xoo) enzymes.