Seven chalcone derivatives were synthesized by the Claisen-Schmidt condensation. The structures of the compounds were confirmed by spectral data (Ultraviolet/visible, infrared, nuclear magnetic resonance and mass spectroscopy). The compounds were tested for their in silico and in vitro antimicrobial and antioxidant activities. The molecular docking assessments showed that all the compounds exhibited good binding affinity with the target microorganism proteins but, compounds 6e and 6g showed better binding affinity compared with the standards. The antimicrobial test revealed that all the compounds screened were active against Staphylococcus aureus and Bacillus subtilis and had minimum inhibitory concentrations (MIC) between 0.4 and 0.6 mg/mL. Compounds 6a, 6c and 6d had moderate activities on Salmonella typhi. Compounds 6b and 6c had moderate activity on Escherichia coli. Compound 6c had moderate activity on Aspergillus niger while compounds 6a and 6e had poor activity. All the compounds except compound 6e had no inhibition against Pseudomonas aeruginosa. The in-vitro antioxidant activity was assessed using ethylenediaminetetraacetate (EDTA) as the standard. Compounds 6c, 6e and 6g gave excellent inhibitory activity better than the standard. Compound 6a gave good activity at 500 μg/mL and 1000 μg/mL concentrations but, below the standard at 250 μg/mL and no inhibition at 125 μg/mL. Compound 6d had good inhibition at 500 μg/mL and 1000 μg/mL but, no inhibition at 125 μg/mL and 250 μg/mL. Compound 6b was found to be inactive in all the concentrations. Absorption, distribution, metabolism and excretion properties of the compounds were assessed using SwissADME. The results of lead likeness showed that compound 6e is a lead-like molecule.

A new series of novel dipeptide sulfonamide analogues were designed, synthesized, and screened for their in silico studies and in vivo antimalarial activities. The synthesized compounds (50 mg/Kg) showed significant activity against P. berghei (NK65) with % inhibition values in (5.9 to 64.7 %) range in when compared with reference drug, artemisinin (66.7 %) in a four day suppressive assay. The in silico studies predicted favorable binding affinity of compounds with target protein residues with high dock score against P. falciparum falcipain 2 (FP-2) and falcipain 3 (FP-3) proteins in comparison with the reference ligands. The synthesized compounds showed druggable properties, and the predicted (absorption, distribution, metabolism, excretion and toxicities (ADMET) properties were within the acceptable limits. Molecular dynamics simulation study of the most active compound, 8 e was performed in order to further validate the stability of the protein-ligand complex and the protein-ligand interactions.

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.