Synthesis, Antimicrobial Activity, and Molecular Docking of Benzoic Hydrazide or Amide Derivatives Containing a 1,2,3‐Triazole Group as Potential SDH Inhibitors

Abstract

The present study was carried out in an attempt to synthesize a new class of antimicrobial agents containing a 1,2,3-triazole motif formed by classical copper catalyzed click chemistry. Antifungal bioassay results showed that five compounds 5a, 5e, 5h, 5j, and 5k possessed a remarkable growth inhibitory activity against Botryosphaeria dothidea, Rhizoctonia solani and Gibberella zeae with EC 50 values within 10.0-0.306 µg/mL. The in vitro efficacy was better than those of the commercial agrochemicals Azoxystrobin, Boscalid, and Fluxapyroxad. In vivo trials showed that compound 5l was effective for the control of rice sheath blight and wheat scab with the effects of 75% and 95%, respectively. Antifungal mechanism studies suggested that target compounds were potential succinate dehydrogenase inhibitors (SDHIs), which were proposed by the agreeable molecular docking study and restrained SDH activity (IC 50 = 3.95 µg/mL, 5l). Interestingly, compounds 5r and 5s displayed good antibacterial activity against phytopathogens. In vivo screening of 5r and 5s against rice bacterial blight afforded a superior control effect (up to 51%) than those of commercial agents Bismerthiazol and Thiodiazole copper. The current studies could support some title compounds to be the lead compounds for exploring highly bioactive antimicrobial substrates, particularly the potential SDHIs.

Comprehensive Overview of Carboxamide Derivatives as Succinate Dehydrogenase Inhibitors

“…Molecular docking analysis showed that the two nitrogen atoms from 1,2,3,-triazole group of compound 68 could form strong hydrogen bonds with the residues Trp173 and Tyr58 of SDH, suggesting that 1,2,3,-triazole could be a promising group to promote the interactions targeting SDH. 104 Longifolene-derived diacylhydrazine compound 69 had inhibitory rates of 97.5, 80.5, 72.1, and 67.1% against P. piricola, C. orbiculare, A. solani, and G. zeae, respectively, presenting excellent and broad-spectrum activity that deserved further study. Molecular docking study revealed that the oxygen atoms of carbonyl and phenol moieties interacted with the residues TRP173 and HIS60 via the H bond, similar to the commercial SDHI carboxin.…”

“…Moreover, compound 68 displayed excellent inhibitory effect against R. solani SDH enzymes with IC 50 value of 3.95 μg/mL, comparable to boscalid (3.15 μg/mL). Molecular docking analysis showed that the two nitrogen atoms from 1,2,3,-triazole group of compound 68 could form strong hydrogen bonds with the residues Trp173 and Tyr58 of SDH, suggesting that 1,2,3,-triazole could be a promising group to promote the interactions targeting SDH . Longifolene-derived diacyl­hydrazine compound 69 had inhibitory rates of 97.5, 80.5, 72.1, and 67.1% against P. piricola , C. orbiculare , A. solani , and G. zeae , respectively, presenting excellent and broad-spectrum activity that deserved further study.…”

Novel Pyrazole-4-acetohydrazide Derivatives Potentially Targeting Fungal Succinate Dehydrogenase: Design, Synthesis, Three-Dimensional Quantitative Structure–Activity Relationship, and Molecular Docking

“…Hydrazide derivatives have attracted continuous concerns as important nitrogenous compounds that were widely utilized in agricultural practices for crop protection. − The most representative types of them are the arylhydrazide derivatives exhibiting antifungal effects against phytopathogenic microorganisms, such as meixiuyihao, fenamidone, and famoxadone (Figure ). ,, Meanwhile, in the structural optimization of bioactive leads, converting the rigid amide bond in bioactive molecules into a flexible hydrazide fragment has been widely regarded as a feasible modification that could strengthen the interactions of constructed molecules with biological enzymes within living organisms. ,, For example, 2 H -chromen-2-one, 1,2,3-triazole, quinazolin-4­(3 H )-one, 1,3,4-oxadiazole, and 1,3,5-thiadiazine-2-thione derivatives bearing an arylhydrazide moiety were further reported for their more salient antifungal effects than those of the corresponding compounds bearing an aryl amide moiety. ,,− Furthermore, our previous work surprisingly found that converting the pyrazole-4-carboxamide fragment of SDHI fungicides into a pyrazole-4-formylhydrazide scaffold could still maintain their inhibitory effects against fungal SDH. , Obviously, the above explorations laid the necessary basis for the development of novel agricultural fungicides bearing an arylhydrazide fragment.…”

Design, Synthesis, and Fungicidal Evaluation of Novel 1,3-Benzodioxole-Pyrimidine Derivatives as Potential Succinate Dehydrogenase Inhibitors

“…In the past decades, the research on new SDHIs mainly focused on the modification of different heterocyclic carboxyl core and substituted aromatic amine moiety. Only some recent studies reported several new SDHI fungicides by modification of the amide bridge. − Two SDHI fungicides with novel amide bridge, isoflucypram and pydiflumetofen, have been successfully developed and commercially utilized, which exhibited significant fungicidal efficacies and low cross-resistance (Figure ). , However, compared with carboxamide derivatives, SDHIs with different scaffolds have rarely been reported.…”