Green Synthesis of Alkenes as Antimicrobial Agents from the Corresponding Formyl Pyrazoles in Aqueous Medium and Insights from Molecular Docking

This study presents a sequence of ecological syntheses of new alkene-pyrazole compounds whose objective is to address the problem of multi-resistant bacteria and fungi (MDR) that arise due to the inappropriate use of traditional antimicrobial drugs. The synthesis procedure involves the condensation of aldehyde pyrazole with different activated methylenes in water. The structures of all synthesized compounds are determined by analyzing their spectral data, specifically the ¹H NMR and ¹³C NMR spectra. The pyrazole unit has been utilized in the synthesis of medicinal drugs. Subsequently, the synthesized alkene-pyrazole compounds were assessed for their potential antimicrobial properties in this particular scenario. This activity was determined against six strains, the obtained results showed that the tested compounds reveled significant antimicrobial activity against gram-negative bacteria to varying degrees, while gram-positive bacteria proved resistance. Biological screening revealed that the inclusion of a functional group of esters methyl-2-cyano-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-enoate and ethyl-2-cyano-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-enoate(or amide 2-cyano-3-(1,3- diphenyl-1H-pyrazol-4-yl)prop-2-enamide and 3-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-2-cyanoprop-2-enamide conferred a greater advantage compared to a benzoxazole or benzothiazole in the alkene-pyrazole also yeast Candida albicans was more sensitive to four compounds methyl 2-cyano-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-enoate,2-cyano-3-(1,3- diphenyl-1H-pyrazol-4-yl)prop-2-enamide, ethyl-2-cyano-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-enoate and 2-cyano-3-(3-methyl-1-phenyl-1H-pyrazol-4-yl)prop-2-enamide. All of the produced compounds exhibited noteworthy activity, as indicated in the results. Furthermore, an in-silico investigation was conducted using AutoDockVina software to normalize and forecast the activities of α-amylase and α-glucosidase as well as predicting the ADMET proprieties in order to determine the pharmacokinetic proprieties of the synthesized compounds.