Synthesis, antimicrobial activity and docking study of some novel 4-(4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino derivatives carrying biologically active sulfonamide moiety

Abstract

A new series of 4-((4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino)-N-(substituted)benzenesulfonamide 3–17, monosubstituted 2-((4-((4-aminophenyl)sulfonyl)phenyl)amino)methylene 18, and its disubstituted derivative 19 were synthesized from the starting material 2-((dimethylamino)methylene)-5,5-dimethylcyclohexane-1,3-dione 2. The crystal structures of compounds 2, 7 and 13 were reported by us through X-ray crystallography. All the prepared compounds were evaluated for their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Clostridium sporogenes), Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli), and antifungal activity against Aspergillus fumigatus, Penicillium chrysogenum, Fusarium oxysporum, Candida albicans. The synthesized compounds displayed interesting antimicrobial activity. Compounds 4 and 12 were the most potent in this study and displayed higher activity compared to the reference drugs, with MIC value of 3.9–31.3μg/mL against a panel of Gram-positive, Gram-negative bacteria and fungi. Molecular modeling was performed inside the active site of dihydropteroate synthase. The synthesized compounds showed similar orientation and binding interactions to that of the co-crystallized ligand inside the binding pocket.