Synthesis of new pyrazoles, thiadiazoles, and trizolotriazines compounds that act as an antibacterial agents using C-ethoxycarbonylhydrazonoyl chloride precursor: Molecular docking simulation and in silico ADMET prediction studies

Abstract

Treatment of C-ethoxycarbonylhydrazonoyl chloride with active methylene-containing compounds such as dibenzoylmethane or malononitrile in sodium ethoxide solution yielded in each case pyrazole derivatives. The latter pyrazoles were used as a useful precursors in the synthesis of new heterocyclic compounds like pyrazoles and 1,3,4-thiadizaoles upon reaction with hydrazonoyl halides. Also, the reaction of C-ethoxycarbonylhydrazonoyl chloride with the approperiate triazinethiones in chloroform in the presence of catalytic amount of triethylamine at reflux yielded the corresponding triazolotriazines. The structures of the newly synthesized compounds were confirmed based on elemental analyses and spectral data. The antibacterial activities were studied against two gram-positive and two gram-negative bacteria, the results represented that compound 26a showed antibacterial activity against Salmonella (22 mm) and E. coli (6 mm), as well as compound 26b against Salmonella (5 mm) and Staphylococcus aureus (10 mm) while the rest compounds showed no antibacterial activities. The molecular docking simulation was investigated for the most active compounds 26a and 26b. The results confirm that compounds 26a and 26b are promising candidates for potential inhibitors of DNA gryA (P37411) of Salmonella and Transpeptidases (Q2FV99) of Staphylococcus aureus.