Fourteen novel dipeptide carboxamide derivatives bearing benzensulphonamoyl propanamide were synthesized and characterized using 1 H NMR, 13 C NMR, FTIR and MS spectroscopic techniques. In vivo antimalarial and in vitro antimicrobial studies were carried out on these synthesized compounds. Molecular docking, haematological analysis, liver and kidney function tests were also evaluated to assess the effect of the compounds on the organs. At 200 mg/kg body weight, 7i inhibited the multiplication of the parasite by 81.38% on day 12 of post-treatment exposure. This was comparable to the 82.34% reduction with artemisinin. The minimum inhibitory concentration (MIC) in µM ranged from 0.03 to 2.34 with 7h having MIC of 0.03 µM against Plasmodium falciparium. The in vitro antibacterial activity of the compounds against some clinically isolated bacteria strains showed varied activities with some of the new compounds showing better activities against the bacteria and the fungi more than the reference drug ciprofloxacin and fluconazole.

The unusual structure and chemical composition of the mycobacterial cell wall, the tedious duration of therapy, and resistance developed by the microorganism have made the recurrence of the disease multidrug resistance and extensive or extreme drug resistance. The prevalence of tuberculosis in synergy with HIV/AIDS epidemic augments the risk of developing the disease by 100-fold. The need to synthesize new drugs that will shorten the total duration of effective treatment and/or significantly reduce the dosage taken under DOTS supervision, improve on the treatment of multidrug-resistant tuberculosis which defies the treatment with isoniazid and rifampicin, and provide effective treatment for latent TB infections which is essential for eliminating tuberculosis prompted this review. In this review, we considered the synthesis and structure activity relationship study of carboxamide derivatives with antitubercular potential.

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, 1H‐nuclear magnetic resonance (NMR), 13C‐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.

Review: 192 refs.

Review: 146 refs.