Antileishmanial and Antitoxoplasmal Activities of 1,4-Dihydropyridines.

ABSTRACT: We have synthesized 24 1,4-dihydropyridine compounds (1,4-DHPs) with different substituents at the aromatic ring by microwave-assisted one-pot Hantzsch multicomponent reaction and evaluated their in vitro activities against and . We have found that compound 9 ((±)-ethyl 2,7,7-trimethyl-4-(2-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) is active against amastigotes (IC₅₀ = 10.6 μM), but it is poorly selective for over Vero cells (SI = 1.13) and macrophages (SI = 0.42). Among the evaluated 1,4-DHPs, compound 4 ((±)-ethyl 4-(4-(benzyloxy)-phenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) is the most active against , providing the lowest IC₅₀ (3.1 μM) and the highest selectivity for this parasite (SI = 5.57) over Vero cells. Docking studies revealed that compound 4 has a high affinity for the target (PDB ID: 4JBV). Furthermore, ADME-T predictions indicated that compound 4 meets the drug-likeness criteria without violating any Lipinski, Veger, or Egan's rules.

SUBMITTER: Oliveira TAS 

PROVIDER: S-EPMC12290673 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature