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Current Organic Chemistry

Author(s): Pratibha Periwal, Ashwani Kumar, Vikas Verma*, Devinder Kumar, Mahavir Parshad, Meenakshi Bhatia and Sourbh Thakur

DOI: 10.2174/0113852728296342240216074100

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Design, Synthesis, and Antimicrobial Evaluation of Novel Sulfonamide Modified with Azoles

Page: [558 - 572] Pages: 15

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Abstract

Sulfonamide, imidazole, and triazole chemical nuclei possess good antimicrobial potential. This study aimed to amalgamate sulfonamide, imidazole, and triazole moieties in a single molecular framework with the intent of improving their antimicrobial activities. The objective of this study was the synthesis of conjugates containing sulfonamide and azole moieties along with in vitro and in silico evaluation as antimicrobial candidates. A series of sulfonamide-modified azoles (7a-r) was synthesized by multicomponent condensation of 1,2-dicarbonyl compounds, ammonium acetate and aryl-substituted aldehydes in glacial acetic acid. The structure of synthesized molecules was elucidated with the help of various spectroscopic techniques, such as FTIR, NMR, and HRMS. The target molecules were tested for in vitro antimicrobial potency against four bacterial strains and two fungal strains. Molecules 7c (MIC 0.0188 μmol/mL), 7f (MIC 0.0170 μmol/mL) and 7i (MIC 0.0181 μmol/mL) were most active against S. aureus and C. albicans. Against E. coli, molecules 7d (MIC 0.0179 μmol/mL), 7f (MIC 0.0170 μmol/mL) and 7i (MIC 0.0181 μmol/mL) were found to be highly active. Moreover, the binding conformations were investigated by in silico molecular docking, and QTAIM (Quantitative theory of atoms in the molecule) analysis was also performed. Molecular properties, such as the heat of formation, HOMO energy, LUMO energy and COSMO volume, were found to be in direct correlation with the antimicrobial potency of molecules 7c, 7f and 7i against S. aureus and C. albicans. All the synthesized molecules were more potent than clinically approved sulfonamides, namely sulfadiazine and sulfabenzamide.

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