NITRO-SUBSTITUTED ARYLSULPHONAMIDE HIS–GLY DIPEPTIDE CARBOXAMIDES AS POTENTIAL ANTIMALARIAL AND ANTITRYPANOSOMAL AGENTS

The need for new antimalarial and antitrypanosomal drugs has increased due to the toxicity of current chemotherapeutics and the development of drug-resistant protozoan parasites. This study determined the synthesis and potential of nitro-substituted arylsulphonamide–his–gly dipeptide carboxamides as antimalarial and antitrypanosomal agents. Several nitro-substituted arylsulphonamide–his–gly dipeptide carboxamide compounds were analysed using in silico, in vitro and in vivo study. The synthetic route involved the preparation of substituted benzenesulphonamide intermediates, followed by coupling with various amino acid-derived carboxamides using EDC/HOBt-mediated peptide bond formation. Final compounds were obtained in good to excellent yields and fully characterized by FTIR, ¹H and ¹³C NMR spectroscopy, HRMS, and melting point analysis, confirming their structural integrity. The in silico, in vitro and in vivo study against Plasmodium and Trypanosoma species shows that some of the compounds exhibited stronger binding affinities, strong antitrypanosomal and antimalarial activity. This study aimed to synthesize arylsulphonamoyl histidine-glycine dipeptide amide derivatives and to investigate their antitrypanosomal and antimalarial properties. We conclude that nitro-substituted arylsulphonamide–his–gly dipeptide carboxamides have high potency for the treatment of malaria and trypanosomiasis even better than some available drugs.