Synthesis, characterization, in vitro antibacterial and in vivo antimalarial studies of arylsulphonamoyl ala-val carboxamide dipeptides

The synthesis of twenty-three (23) new ala-val dipeptides carboxamides bearing the sulphonamide functionality are reported. This was achieved by first reacting substituted and unsubstituted benzene sulphonyl chlorides with alanine to give three substituted and unsubstituted benzene sulphonamoyl alkanoic acids (1a-c) . Secondly, boc-protected valine carboxamide (carbamate) derivatives (2a-h) were prepared by reacting boc-valine with various primary and secondary aliphatic amines as well as with alicyclic and aromatic amine heterocycles aided by peptide coupling reagents. The carbamates were deprotected and the free amines reacted with the already prepared substituted and unsubstitutedbenzenesulphonamoyl alkanoic acid derivatives aided by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride/hydroxybenzotriazole (peptides coupling reagents) to give the substituted and unsubstituted ‘ala-val’ dipeptide carboxamide derivatives bearing the sulphonamide functionality ( 3a-w ). All the synthesized compounds were characterized using FTIR, ¹ H and ¹³ C-NMR and ESI- and APCI- MS, and the spectra of the compounds were in agreement with the assigned structures. The In vitro antimicrobial study revealed that most compounds were active against the tested organisms. Compounds 3c and 3d were observed to be the most active against E. coli (G-)/ Staphylococcus aureus (G+) and trypanosome at zone of inhibition (29 mm) and minimum inhibitory concentration (MIC) of 6.25 and 3.125 µg/mL respectively. The compounds showed moderate to good in vivo antimalarial activity, and compound 3t exhibited the highest percentage (%) inhibition of 73.81. Compound 3s showed the highest % parasitemia (29.55) compared with the 36.96% parasitemia for the negative control.