1. Tetrahydropyridine appended 8-aminoquinoline derivatives: Design, synthesis, in silico, and in vitro antimalarial studies.
- Author
-
Sharma G and Sharma CS
- Subjects
- Humans, Dose-Response Relationship, Drug, Molecular Docking Simulation, Molecular Structure, Pyridines chemistry, Pyridines pharmacology, Pyridines chemical synthesis, Structure-Activity Relationship, Aminoquinolines chemistry, Aminoquinolines pharmacology, Aminoquinolines chemical synthesis, Antimalarials pharmacology, Antimalarials chemical synthesis, Antimalarials chemistry, Drug Design, Parasitic Sensitivity Tests, Plasmodium falciparum drug effects
- Abstract
Antimalarial drug resistance is a major obstacle in the ongoing quest against malaria. The disease affects half of the world's population. The majority of them are toddlers and pregnant women. Needed a potent compound to act on drug-resistant Pf at appropriate concentrations without endangering the host. Envisaged solving this issue through rational drug design by creating a novel hybrid drug possessing two pharmacophores that can act on two marvellous and independent aims within the cell. Synthesized a new series of substituted 4-phenyl-1,2,3,6-tetrahydropyridine (THP) 8-Aminoquinoline-based hybrid analogs which have been integrated with quinoline, chloroquine, pamaquine, and primaquine, which exhibited antimalarial activity against Pf. Out of thirteen 4-phenyl-1,2,3,6-THP appended 8-Aminoquinoline derivatives, the compounds 1j, 1e, 1b, and 1l have exhibited good antimalarial activity against chloroquine-sensitive (3D7) and chloroquine-resistant (RKL-9) strain with the minimum inhibitory concentration. Compound 1b was the most effective and showed consistently good potency against the drug-resistant (RKL-9) strain, although all other arrays showed good antimalarial efficacy. Additional docking and molecular dynamics studies were carried out at several targeting sites to quantify the structural parameters necessary for the activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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