Design, Synthesis, Antimicrobial Activity and Molecular Docking of Novel Pyridine, Thiophene, and Thiadiazole Scaffolds Utilizing 2-Cyano-N-(4-(1-(2-(2-cyanoacetyl)hydrazineylidene)ethyl)phenyl)acetamide

An efficient protocol is reported for synthesizing arylidene adducts, pyridine derivatives, in excellent yields by treating 2-cyano-N-(4-(1-(2-(2-cyanoacetyl) hydrazineylidene) ethyl)phenyl)acetamide with quinoline-3-carbaldehydes, 2-arylidenemalononitriles, and acetylacetone in EtOH, respectively. In addition, dithiadiazole and dithiophene adducts were synthesized from one pot reaction using phenyl isothiocyanate, and either hydrazonyl chloride or 2-bromo-1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazole-4-yl)ethan-1-one in DMF containing potassium hydroxide. The structure of novel products was elucidated using spectroscopic data and elemental analyses. The synthesized compounds were evaluated for their antimicrobial activities. The compounds showed antibacterial and antifungal activities against the tested G-ve and G+ve bacteria and against the tested fungi. The MIC was mostly in the range of 100-500 μg/mL. Molecular docking was used to analyse interactions between the compounds and antimicrobial target proteins. The molecular docking simulation showed lower binding energy with different types of interaction at the active site of Sterol 14-demethylase of C. albicans, Fdc1 proteins of A. niger, DNA Gyrase of E. coli, and LasR, an activator of exotoxin. An expression of P. aeruginosa indicates that these compounds could inhibit the enzyme and cause promising antimicrobial effects.