In vitro and in vivo antiplasmodial activity of novel quinoline derivative compounds by molecular hybridization
| Autor: | Giovana de Almeida Pimentel, Daniel Silqueira Martins Guimarães, Fernando de Pilla Varotti, Maribel Navarro, Henrique Pereira, Adilson David da Silva, Juliane Aparecida Marinho, Izabelle Karine da Costa Nunes, Clarice Abramo, Nícolas Glanzmann |
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| Rok vydání: | 2021 |
| Předmět: |
Hemeproteins
Erythrocytes In silico Plasmodium falciparum Hemolysis 01 natural sciences Cell Line Antimalarials Mice 03 medical and health sciences chemistry.chemical_compound Chloroquine In vivo Drug Discovery medicine Animals Humans Cytotoxicity 030304 developmental biology Pharmacology 0303 health sciences 010405 organic chemistry Organic Chemistry Quinoline General Medicine Condensation reaction In vitro Malaria 0104 chemical sciences chemistry Biochemistry Quinolines Hemin Female Growth inhibition medicine.drug |
| Zdroj: | European Journal of Medicinal Chemistry. 215:113271 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2021.113271 |
| Popis: | Chloroquine (CQ) has been the main treatment for malaria in regions where there are no resistant strains. Molecular hybridization techniques have been used as a tool in the search for new drugs and was implemented in the present study in an attempt to produce compound candidates to treat malarial infections by CQ-resistant strains. Two groups of molecules were produced from the 4-aminoquinoline ring in conjugation to hydrazones (HQ) and imines (IQ). Physicochemical and pharmacokinetic properties were found to be favorable when analyzed in silico and cytotoxicity and antiplasmodial activity were assayed in vitro and in vivo showing low cytotoxicity and selectiveness to the parasites. Candidates IQ5 and IQ6 showed important values of parasite growth inhibition in vivo on the 5th day after infection (IQ5 15 mg/kg = 72.64% and IQ6 15 mg/kg = 71.15% and 25 mg/kg = 93.7%). IQ6 also showed interaction with ferriprotoporphyrin IX similarly to CQ. The process of applying condensation reactions to yield imines is promising and capable of producing molecules with antiplasmodial activity. |
| Databáze: | OpenAIRE |
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