Synthesis and biological evaluation of Val-Val dipeptide-sulfonamide conjugates

Abstract

Novel Val-Val dipeptide-benzenesulfonamide conjugates were reported in this study. These were achieved by a condensation reaction of p-substituted benzenesulfonamoyl alkanamides with 2-amino-4-methyl-N-substituted phenyl butanamide using classical peptide-coupling reagents. The compounds were characterized using Fourier transform infrared, ¹ H-nuclear magnetic resonance (NMR), ¹³ C-NMR, and electrospray ionization-high-resolution mass spectrometry spectroscopic techniques. As predicted from in silico studies, the Val-Val dipeptide-benzenesulfonamide conjugates exhibited antimalarial and antioxidant properties that were analogous to the standard drug. The synthesized compounds were evaluated for in vivo antimalarial activity against Plasmodium berghei. The hematological analysis was also conducted on the synthesized compounds. At 50 mg/kg body weight, compounds 8a, 8d, and 8g-i inhibited the multiplication of the parasite by 48-54% on Day 7 of posttreatment exposure, compared with the 67% reduction with artemisinin. All the synthesized dipeptides had a good antioxidant property, but it was less when compared with vitamin C. The dipeptides reported herein showed the ability to reduce oxidative stress arising from the malaria parasite.

Keywords: Val-Val dipeptide; antimalarial; antioxidant; benzenesulfonamide; drug resistance; in silico studies.