1. Academic Validation
  2. Antileishmanial and Antitoxoplasmal Activities of 1,4-Dihydropyridines

Antileishmanial and Antitoxoplasmal Activities of 1,4-Dihydropyridines

  • ACS Omega. 2025 Jul 10;10(28):31066-31076. doi: 10.1021/acsomega.5c04551.
Thaís A S Oliveira 1 Yan R Robles 1 Ibrahim S Al Nasr 2 Waleed S Koko 2 Tariq A Khan 3 Ismail Daoud 4 5 Seyfeddine Rahali 6 Noureddine Amdouni 7 Ridha B Said 6 Antônio E M Crotti 1
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Philosophy, Sciences, and Letters at Ribeirão Preto, University of São Paulo, Ribeirão Preto 14900-001, São Paulo, Brazil.
  • 2 Department of Biology, College of Science, Qassim University, Qassim 51452, Saudi Arabia.
  • 3 Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Qassim 51452, Saudi Arabia.
  • 4 Department of Matter Sciences, University Mohamed Khider, BP 145 RP, Biskra 07000, Algeria.
  • 5 Laboratory of Natural and Bio-Active Substances, Faculty of Science, Tlemcen University, Tlemcen 13000 P.O. Box 119, Algeria.
  • 6 Department of Chemistry, College of Science, Qassim University, Qassim 51452, Saudi Arabia.
  • 7 Laboratoire de Caracte'risations, Applications et Mode'lisations des Mate'riaux, Faculte' des Sciences de Tunis, Universite' Tunis El Manar, Tunis 1068, Tunisia.
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.

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