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.

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.

: Carbohydrazides and their Schiff bases are important classes of heterocycles that are not only employed in the area of organic chemistry but also have tremendous applications in physical and inorganic chemistry. A series of potentially bioactive compounds containing carbohydrazide functionality and their hydrazone derivatives have been synthesized and screened for antibacterial, anticancer, antifungal and anti-inflammatory, etc. This brief review discloses some synthetic routes to so many reported carbohydrazides, their Schiff bases, their biological activities, and their structure-activity relationship.