Synthesis and antimalarial and anticancer evaluation of 7-chlorquinoline-4-thiazoleacetic derivatives containing aryl hydrazide moieties
Language English Country Germany Media print-electronic
Document type Journal Article
- Keywords
- antimalarial, antiproliferative, apoptosis, hydrazides, quinoline, thiazol,
- MeSH
- Antimalarials chemical synthesis chemistry pharmacology MeSH
- Apoptosis drug effects MeSH
- A549 Cells MeSH
- Quinolines chemical synthesis chemistry pharmacology MeSH
- Hydrazines chemical synthesis chemistry pharmacology MeSH
- Inhibitory Concentration 50 MeSH
- Cell Cycle Checkpoints drug effects MeSH
- Acetic Acid chemical synthesis chemistry pharmacology MeSH
- Humans MeSH
- Malaria drug therapy MeSH
- MCF-7 Cells MeSH
- Disease Models, Animal MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Antineoplastic Agents chemical synthesis chemistry pharmacology MeSH
- Thiazoles chemical synthesis chemistry pharmacology MeSH
- Cell Survival drug effects MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antimalarials MeSH
- Quinolines MeSH
- Hydrazines MeSH
- Acetic Acid MeSH
- Antineoplastic Agents MeSH
- Thiazoles MeSH
Twelve 7-chloroquinoline derivatives were designed and synthesized using the principle of molecular hybridization through the coupling of 2-[2-(7-chloroquinolin-4-ylthio)-4-methylthiazol-5-yl]acetic acid 1 with various benzoyl hydrazines 2a-l. The synthetic compounds were tested as antimalarials. Some of them showed an efficient in vitro activity as inhibitors of β-hematin formation and an in vivo activity in a murine model, resulting in compounds 8 and 9 as the most active ones with IC50 values of 0.65 ± 0.09 and 0.64 ± 0.16 µM, respectively. The effects of the compounds on the cell viability, cell cycle, and apoptosis induction of A549 and MCF-7 cancer cell lines were also examined. Our data showed that compounds 6 and 12 were the most active agents, decreasing the cell viability of MCF-7 cells with IC50 values of 15.41 and 12.99 µM, respectively. None of the compounds analyzed significantly affected the viability of peripheral blood mononuclear cells. Also, significant induction of apoptosis was observed when both cancer cell lines were incubated with compounds 6 and 12. In MCF-7 cells, treatment with these compounds led to cell cycle arrest in the G0/G1 phase. The results obtained suggest that these structures may be useful in developing new therapies for malaria and cancer treatment.
Biotechnology Unit Faculty of Pharmacy Central University of Venezuela Caracas Venezuela
Facultad de Medicina Universidad de Las Américas Quito Ecuador
Institute of Immunology Faculty of Medicine Central University of Venezuela Caracas Venezuela
Organic Synthesis Laboratory Faculty of Pharmacy Central University of Venezuela Caracas Venezuela
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