Synthesis, molecular docking and pharmacological investigation of some 4-methylphenylsulphamoyl carboxylic acid analogs

Abstract

Compounds bearing sulphonyl and amino acid moieties are considered the basis for sulfa drug development. The synthesis of 4-methylphenylsulphamoyl carboxylic acids and the evaluation of their pharmacological activities are reported. The synthesis of these compounds was accomplished by the reaction of various α-amino acids and 4-methyl phenyl sulphonyl chloride in basic aqueous solution. Structures were confirmed by FTIR,1HNMR,13CNMR spectra and elemental analytical data. Molecular docking interactions of the analogues were determined using PyRx. In the in vitro antimicrobial activity analysis, compounds 1, 3, 5 and 7 had antimicrobial inhibitory concentration range of 0.5-1.0mg/ml comparable with 0.1-2.0mg/ml of ofloxacin and fluconazole. In the in vitro anti-oxidant activity study compounds 1, 2 and6 displayed half-maximal inhibitory concentrations (IC50) of 1.104±0.001 µg/ml, 1.159±0.002µg/ml and1.240±0.001µg/ml respectively comparable with 0.999±0.002µg/ml of ascorbic acid. In the molecular docking study, compound 4 had a strong 2D binding interaction with plasmepsin II amino acid residue and compounds 1, 3, 4, 5, 6 and 7 had in silico antimicrobial, anti-oxidant, antitrypanosomal and antimalarial properties similar to their standard drugs. Considering the outstanding pharmacological properties and their strict compliance with Lipinski’s rule, the synthesized 4methylphenylsulphamoyl analogues could be considered as antimicrobial, antimalarial, antitrypanosomal and anti-oxidant drug candidates.