Synthesis and Biological Evaluation of Alanine Derived Bioactive p-Toluenesulphonamide Analogs

Abstract

Sulphonamides and carboxamides have great pharmacological importance. The purpose of the study was to synthesize alanine-derived bioactive sulphonamides bearing carboxamides and evaluate their biological activities. The reaction of p-toluenesulphonyl chloride with L-alanine afforded compound 1, which was acetylated to obtain compound 2. The chlorination and ammonolysis of compound 2 gave the carboxamide backbone (3) which was coupled with aryl/heteroaryl halides to afford the hybrid compounds 4, 5 and 6. Structures were confirmed by FTIR, 1H-NMR, 13C-NMR spectra and elemental analytical data. The in vitro antimicrobial properties were determined by agar dilution, and the antioxidant properties were also investigated. Molecular docking interactions of the analogues were determined using PyRx. Compounds 4, 5 and 6 exhibited excellent in vitro antimicrobial properties in the range of 0.5-1.0mg/ml while compounds 1and 2 had half-maximal inhibitory concentration (IC50) of 1.11±0.15µg/ml and 1.12±0.13µg/ml respectively. For the molecular docking studies, compounds 5 and 6 displayed the best antitrypanosomal activity with binding affinities of -13.95 and -13.51kcal/mol respectively while compound 4 showed the highest in silico antimalarial activity having binding affinity of -11.95kcal/mol. All the alanine derived sulphonamides were observed to be potential antimicrobial, antioxidant, antitrypanosomal and antimalarial agents following the biological activities studies.