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.

Chromenopyrazolones, tosylchromenopyrazolones and benzoylcoumarins were prepared by the reaction of salicylaldehyde tosylhydrazones with 3‐oxobutanoates. The title compounds were screened for their in vitro anti‐microbial, DPPH, ABTS.+ free radical scavenging, α‐glucosidase inhibitory and anti‐inflammatory activities. The bioactivity profile studies revealed that the trifluoromethyl chromenopyrazolones were effective for anti‐microbial activity. Trifluoromethyl chromenopyrazolones 5 h, 5 j, 5 l, tosyl chromenopyrazolones 5 m‐q and benzoylcoumarin 6 g are the promising α‐glucosidase inhibitors. The methyl chromenopyrazolones 5 b‐d, trifluoromethyl chromenopyrazolones 5 h‐l, tosylchromenopyrazolone 5 m and methoxy benzoylcoumarin 6 h denoted promising anti‐inflammatory activity.

A facile approach has been developed for the preparation of chromenopyrazolones (5a–o, 7a–k) by the reaction of salicylaldehyde phenylhydrazones (3a–o) with β-ketoesters (4a, 4f–g) and activated alkynes (6a–e) in the presence of La(OTf)3 with good yields.