Microwave-assisted synthesis of hybrid PABA-1,3,5-triazine derivatives as an antimalarial agent.
J Biochem Mol Toxicol
; 35(9): e22860, 2021 Sep.
Article
em En
| MEDLINE
| ID: mdl-34313355
ABSTRACT
The present manuscript deals with the development of novel p-aminobenzoic acid (PABA) associated 1,3,5-triazine derivatives as antimalarial agents. The molecules were developed via microwave-assisted synthesis and structures of compounds were ascertained via numerous analytical and spectroscopic techniques. The synthesized compounds were also subjected to ADMET analysis. In a docking analysis, the title compounds showed high and diverse binding affinities towards wild (-162.45 to -369.38 kcal/mol) and quadruple mutant (-165.36 to -209.47 kcal/mol) Pf-DHFR-TS via interacting with Phe58, Arg59, Ser111, Ile112, Phe116. The in vitro antimalarial activity suggested that compounds 4e, 4b, and 4h showed IC50 ranging from 4.18 to 8.66 µg/ml against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum. Moreover, compounds 4g, 4b, 4e, and 4c showed IC50 ranging from 8.12 to 12.09 µg/ml against chloroquine-resistant (Dd2) strain. In conclusion, our study demonstrated the development of hybrid PABA substituted 1,3,5-triazines as a novel class of Pf-DHFR inhibitor for antimalarial drug discovery.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
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Triazinas
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Micro-Ondas
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Antimaláricos
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article