Quinolinotriazole antiplasmodials via click chemistry: synthesis and in vitro studies of 7-Chloroquinoline-based compounds
| Autor: | Alaíde Braga de Oliveira, Pedro Henrique De Almeida Simões Neves, Jordano Augusto Carvalho Sousa, Geraldo Célio Brandão, Guilherme R. Pereira, Juliana Braga de Oliveira Santos, Maria Fernanda Alves do Nascimento, Andreza Cristina Gomes Ferreira, Erick Bruman Souza Gomes |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
biology
Chemistry Quinoline Plasmodium falciparum Drug resistance 7-Chloroquinolinotriazoles biology.organism_classification Combinatorial chemistry Cycloaddition In vitro Antimalarial activity RS1-441 chemistry.chemical_compound Pharmacy and materia medica Chloroquine Click chemistry medicine Quinolines Click reaction Cytotoxicity medicine.drug |
| Zdroj: | Brazilian Journal of Pharmaceutical Sciences, Volume: 57, Article number: e181086, Published: 26 NOV 2021 Brazilian Journal of Pharmaceutical Sciences, Vol 57 (2021) |
| Popis: | Malaria is nowadays one of the most serious health concerns in a global scale and, although there is an evident increase in research studies in this area, pointed by the vast number of hits and leads, it still appears as a recurrent topic every year due to the drug resistance shown by the parasite exposing the urgent need to develop new antimalarial medications. In this work, 38 molecules were synthesized via copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) or “click” chemistry, following different routes to produce 2 different organic azides, obtained from a 4,7 dicholoquinoline, reacted with 19 different commercially available terminal alkynes. All those new compounds were evaluated for their in vitro activity against the chloroquine resistant malaria parasite Plasmodium falciparum (W2). The cytotoxicity evaluation was accomplished using Hep G2 cells and SI index was calculated for every molecule. Some of the quinoline derivatives have shown high antimalarial activity, with IC50 values in the range of 1.72-8.66 µM, low cytotoxicity, with CC50>1000 µM and selectivity index (SI) in the range of 20-100, with some compounds showing SI>800. Therefore, the quinolinotriazole hybrids could be considered a very important step on the development of new antimalarial drugs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|