Design, Synthesis, Antimalarial Activity and Docking Study of 7-Chloro-4- (2-(substituted benzylidene)hydrazineyl)quinolines.
7-Chloro-4-(2-(substituted benzylidene)hydrazineyl)quinolines
Malaria
P. falciparum
antimalarial
drug resistance
plasmepsin 2 inhibitors
Journal
Medicinal chemistry (Shariqah (United Arab Emirates))
ISSN: 1875-6638
Titre abrégé: Med Chem
Pays: Netherlands
ID NLM: 101240303
Informations de publication
Date de publication:
2020
2020
Historique:
received:
29
03
2019
revised:
10
07
2019
accepted:
22
07
2019
pubmed:
7
8
2019
medline:
3
6
2021
entrez:
7
8
2019
Statut:
ppublish
Résumé
Malaria is a growing infectious disease burden due to the increasing emergence of resistant strains of Plasmodium falciparum. Because of the limited therapeutic efficacy of available antimalarial drugs, the development of potent antimalarial drug agents is therefore an urgent requirement to fight against resistant malaria. The objective of this work was to develop novel quinoline-baed antimalarial agents that would be active against resistant P. falciparum malaria. Some 7-chloro-4-(2-(substituted benzylidene)hydrazineyl)quinolines were synthesized for the evaluation of their potential as possible antimalarial agents, particularly against resistant malaria. The antimalarial activity of synthesized compounds was evaluated in vitro against bloodstage parasites of P. falciparum. Further, molecular docking and drug-likeness including ADMET (Absorption, Distribution, Metabolism, Elimination and Toxicity) studies were also carried out using in silico tools. Results reveal the in vitro antimalarial activity of synthesized 7-chloro-4-(2-(substituted benzylidene)hydrazineyl)quinolines against P. falciparum. The docking study investigates the antimalarial effectiveness of synthesized quinolines as novel plasmepsin 2 inhibitors. Drug-likeness prediction exhibits acceptable drug-likeness and ADMET properties. Based upon our findings, it is concluded that the molecular scaffold of 7-chloro-4-(2- (substituted benzylidene)hydrazineyl)quinolines may be used as a lead structure for further modifications in the search of more potent antimalarial drug molecules.
Sections du résumé
BACKGROUND
BACKGROUND
Malaria is a growing infectious disease burden due to the increasing emergence of resistant strains of Plasmodium falciparum. Because of the limited therapeutic efficacy of available antimalarial drugs, the development of potent antimalarial drug agents is therefore an urgent requirement to fight against resistant malaria.
OBJECTIVE
OBJECTIVE
The objective of this work was to develop novel quinoline-baed antimalarial agents that would be active against resistant P. falciparum malaria.
METHODS
METHODS
Some 7-chloro-4-(2-(substituted benzylidene)hydrazineyl)quinolines were synthesized for the evaluation of their potential as possible antimalarial agents, particularly against resistant malaria. The antimalarial activity of synthesized compounds was evaluated in vitro against bloodstage parasites of P. falciparum. Further, molecular docking and drug-likeness including ADMET (Absorption, Distribution, Metabolism, Elimination and Toxicity) studies were also carried out using in silico tools.
RESULTS
RESULTS
Results reveal the in vitro antimalarial activity of synthesized 7-chloro-4-(2-(substituted benzylidene)hydrazineyl)quinolines against P. falciparum. The docking study investigates the antimalarial effectiveness of synthesized quinolines as novel plasmepsin 2 inhibitors. Drug-likeness prediction exhibits acceptable drug-likeness and ADMET properties.
CONCLUSION
CONCLUSIONS
Based upon our findings, it is concluded that the molecular scaffold of 7-chloro-4-(2- (substituted benzylidene)hydrazineyl)quinolines may be used as a lead structure for further modifications in the search of more potent antimalarial drug molecules.
Identifiants
pubmed: 31385774
pii: MC-EPUB-100155
doi: 10.2174/1573406415666190806154722
doi:
Substances chimiques
Antimalarials
0
Quinolines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
928-937Informations de copyright
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