New chalcone derivatives as potential antimicrobial and antioxidant agent.

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.

Novel Leu-Val Based Dipeptide as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking.

The increase of antimicrobial resistance (AMR) and antimalarial resistance are complex and severe health issues today, as many microbial strains have become resistant to market drugs. The choice for the synthesis of new dipeptide-carboxamide derivatives is as a result of their wide biological properties such as antimicrobial, anti-inflammatory, and antioxidant activities. The condensation reaction of substituted benzenesulphonamoyl pentanamides with the carboxamide derivatives using peptide coupling reagents gave targeted products (8a-j). The in silico antimalarial and antibacterial studies showed good interactions of the compounds with target protein residues and a higher dock score in comparison with standard drugs. In the in vivo study, compound 8j was the most potent antimalarial agent with 61.90% inhibition comparable with 67% inhibition for Artemisinin. In the in vitro antimicrobial activity, compounds 8a and 8b (MIC 1.2 × 10-3 M and 1.1 × 10-3 M) were most potent against S. aureus; compound 8a, 8b, and 8j with MIC 6.0 × 10-3 M, 5.7 × 10-4 M, and 6.5 × 10-4 M, respectively, were the most active against B. subtilis; compound 8b (MIC 9.5 × 10-4 M) was most active against E.coli while 8a, 8b and 8d were the most active against S. typhi. Compounds 8c and 8h (MIC 1.3 × 10-3 M) each were the most active against C. albicans, while compound 8b (MIC 1.3 × 10-4 M) was most active against A. niger.

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

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.