Synthesis of substituted arylsulphonamoyl 'Leu-Gly' dipeptide carboxamide derivatives containing antimalarial and other related diseases pharmacological properties

The preparation and characterization of new substituted arylsulphonamoyl 'Leu-Gly' dipeptide carboxamide derivatives 8a-8l were carried out and reported in this research. The derivatives displayed different values of interactions with the protein residues, 2DHN, 1WXH, 24D7 and 4Z22I for S. aureus, B. subtilis, E.coli and P. falciparum respectively for molecular docking studies. Biological studies (in vitro antimicrobial, in vivo antimalarial, haematological as well liver and kidney analyses of the derivatives were also conducted. Derivative 8f gave the highest binding interaction values (10.3, 10.8, 9.5 and 9.2 kcal mol-1) respectively for the residues. The in vitro antimicrobial studies revealed derivatives 8a - 8f with MIC values in the range (0.5-1.0) mg/mL, however, derivative 8f displayed the best MIC result (0.5-0.6) mg/mL. The derivatives gave percentage parastemia inhibition in the range (31.6-70.12) % on the fourth day after the mice were fed with 50 mg/kg of the derivatives for three days. Derivative 8e gave the highest inhibition result of 70.12 % comparable to others. Hematological, liver and kidney function tests showed that the derivatives exhibited no toxicities when 50 kg body weights were given to the mice.