Synthesis,Structure And Bioactivity Of Schiff Base Derivatives Based On1,2,4-Triazole

In recent years,Schiff base compounds have attracted much attention because of their diverse biological activities?especially antifungal activity?.Therefore,the design and synthesis of Schiff base compounds with different structures and systematically studying their structure and properties are the key points for the development and promotion of new antifungal drugs.The fourteen schiff base compounds were synthesized and characterized by melting point,elemental analysis,infrared spectrum,nuclear magnetic resonance spectrum and X-single crystal diffraction,the crystal structure and the weak intermolecular interactions were discussed,the antifungal activity of the compounds was measured and molecular docking was also carried out.Three 5-alkyl-substituted-4-amino-1,2,4-triazole-3-thione intermediates were obtained by reflux reaction with acetic acid,propionic acid and n-butyric acid in anhydrous ethanol.Four 5-alkyl-substituted-4-amino-1,2,4-triazole-3-thione intermediates were obtained from 4-methoxybenzoic acid,3-methoxybenzoic acid,2-methoxy-benzoic acid and 3-methylbenzoic acid by four-step reaction?i.e.esterification,hydrazylation,salt formation and ring formation?.The obtained seven intermediates were refluxed with 2,4-dinitrobenzaldehyde?2,4,6-trimethylbenzal-dehyde?in glacial acetic acid to obtain fourteen schiff base derivatives?named Ia-g,IIa-g?and their structure were also characterized.Single crystals of nine compounds?Ia-g,IIc and IIg?were obtained by slow solvent volatilization and their structures were analyzed in detail.Crystal explorer software was used to study the molecular indirect contacts of crystal structure and the interaction between donor and acceptor groups.Through analysis of the hirshfeld surface(d_norm,shape index and curvature)and the 2D fingerprint contribution rate,the intermolecular hydrogen bonds and other weak interactions are deeply discussed,and the mechanism of crystal stacking mode was also explained,which provides a guidance for drug design.The bioactivities of fourteen compounds against five fungi?Botryosphaeria berengriana,Wheat gibberellic,Potato dry rot fungus,Botryo sphaeria ribis,Maize rough dwarf virus?were measured,and the results showed that all compounds?except Ia?had the best antifungal on Wheat gibberellic than that of others.To better understand the antifungal mechanism of the substance,the protein CYP51 of Fusarium graminearum,the pathogenic gene of wheat scab,was used as the receptor protein,and the molecular docking method was adopted to simulate the theoretical docking of fourteen compounds,which theoretically provides the research direction for drug design.