Diethyl 4-(1-aryl-3-(ethoxycarbonyl)-1H-pyrazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates as possible antitubercular agents: Synthesis, ADME profiling, and in silico screening through molecular docking

Abstract

A method for the synthesis of diethyl 4-(1-aryl-3-(ethoxycarbonyl)-1H-pyrazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates was developed via a modified Hantzsch three-component cyclocondensation. High structural similarity to known lead antitubercular agents was found using Tanimoto coefficients. In silico screening through molecular docking were performed on key enzymes of Mycobacterium tuberculosis, including DprE1, InhA, MmpL3, PknB, and DNA gyrase. The results suggested that the synthesized compounds exhibited high affinity for these targets, particularly for PknB and InhA. Furthermore, predicted ADME-Tox parameters and BOILED-Egg profiling suggests high gastrointestinal absorption and favourable drug-likeness. The findings indicate the potential of these pyrazole-substituted dihydropyridines for further development as antitubercular agents.