Advances in the synthesis of dehydroacetic acid based pyrazole-pyridine conjugates with promising anti-malarial and anti-inflammatory potentials.

AIMS: This study aimed to design and synthesize novel dehydroacetic acid (DHA) based pyrazole - pyridine conjugates and evaluate their potential efficacy in combating inflammation and malaria.

MATERIALS AND

METHODS

A molecular hybridization strategy was employed to integrate the pyridine nucleus with two biologically active scaffolds, DHA and pyrazole. The target compounds were synthesized through a multi-step route involving the condensation of DHA with formyl-substituted pyrazoles to yield chalcone intermediates, followed by cyclization with malononitrile and ammonium acetate. The synthesized compounds were analyzed using spectroscopic techniques and tested in vitro for their anti-malarial and anti-inflammatory effects. Molecular docking studies were performed using PyRx 0.8 to predict binding interactions with key target enzymes - Enoyl-acyl-carrier-protein reductase (PDBID: 1NHG) and Cyclooxygenase-2 (PDB ID: 3LN1).

RESULTS

Among the synthesized series, compound 5c exhibited the most potent activities, with an IC₅₀ of 0.96 ± 0.09 µM against Plasmodium falciparum and IC₅₀ of 7.23 ± 0.14 µM for significant anti-inflammatory activity. Docking results supported strong affinity toward both target enzymes.

CONCLUSIONS

The findings demonstrate that DHA based pyrazole - pyridine hybrids are promising dual-action scaffolds with significant anti-malarial and anti-inflammatory potential.