Synthesis and Pesticidal Activity of New Niacinamide Derivatives Containing a Flexible, Chiral Chain

Natural products are a source for pesticide or drug discovery. In order to discover lead compounds with high fungicidal or herbicidal activity, new niacinamide derivatives derived from the natural product niacinamide, containing chiral flexible chains, were designed and synthesized. Their structures were confirmed by H-1 NMR, C-13 NMR and HRMS analysis. The fungicidal and herbicidal activities of these compounds were tested. The fungicidal activity results demonstrated that the compound (S)-2-(2-chloronicotinamido)propyl-2-methylbenzoate (3i) exhibited good fungicidal activity (92.3% inhibition) against the plant pathogen Botryosphaeria berengriana at 50 mu g/mL and with an EC50 of 6.68 +/- 0.72 mu g/mL, which is the same as the positive control (fluxapyroxad). Compound 3i was not phytotoxic and could therefore be used as a fungicide on crops. Structure-activity relationships (SAR) were studied by molecular docking simulations with the succinate dehydrogenase of the fungal mitochondrial respiratory chain.

Automated summary

New niacinamide derivatives containing chiral flexible chains were synthesized for the discovery of lead compounds with high fungicidal or herbicidal activity. The compound (S)-2-(2-chloronicotinamido)propyl-2-methylbenzoate (3i) exhibited good fungicidal activity against Botryosphaeria berengriana, with similar potency as the positive control. Compound 3i showed no phytotoxicity and could be used as a fungicide on crops. Molecular docking simulations were conducted to study the structure-activity relationships (SAR) with the fungal succinate dehydrogenase.