Synthesis and pesticidal activity of new niacinamide derivatives containing a flexible, chiral chain

Authors: WEI, ZHE-CHENG - Zhejiang University Of Technology; WANG, QIA0 - Zhejiang University Of Technology; MIN, LI-JING - Huzhou University; Bajsa-Hirschel, Joanna; Cantrell, Charles; HAN, LIANG - Huzhou University; TAN, CHENG-XIA - Zhejiang University Of Technology; WENG, JIAN-QUAN - Zhejiang University Of Technology; LIU, XING-HAI - Zhejiang University Of Technology; DUKE, STEPHEN - University Of Mississippi

Submitted to: Molecules
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/13/2022
Publication Date: 12/21/2022
Citation: Wei, Z., Wang, Q., Min, L., Bajsa Hirschel, J.N., Cantrell, C.L., Han, L., Tan, C., Weng, J., Liu, X., Duke, S.O. 2022. Synthesis and pesticidal activity of new niacinamide derivatives containing a flexible, chiral chain. Molecules. https://doi.org/10.3390/molecules28010047.
DOI: https://doi.org/10.3390/molecules28010047

Interpretive Summary: Natural products have diverse structures, high biological activities and novel mechanisms of action. Therefore, they are a rich source for pesticide discovery. Nicotine is a class of pyridine type natural products which was first found in tobacco. Nicotine has the effects of killing insects and regulating human physiological activities. Nicotine is also an important intermediate in the synthesis of the natural product niacin and niacinamide, which are essential vitamins for human. Nicotine acid derivatives can be found in many plant or microbial secondary metabolites. In order to discover lead compounds with high fungicidal or herbicidal activity, new niacinamide derivatives containing chiral flexible chains were designed and synthesized derived from the natural product niacinamide. The fungicidal and herbicidal activities of these compounds were tested.

Technical Abstract: 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 containing chiral flexible chains were designed and synthesized derived from the natural product niacinamide. Their structures were confirmed by 1H NMR, 13C 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 µg/mL and the EC50 is 6.68±0.72 µg/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.