Design, synthesis and molecular docking study of novel triazole-quinazolinone hybrids as antimalarial and antitubercular agents.
Bioorg Med Chem Lett
; 108: 129800, 2024 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-38763480
ABSTRACT
In a quest to discover new antimalarial and antitubercular drugs, we have designed and synthesized a series of novel triazole-quinazolinone hybrids. The in vitro screening of the triazole-quinazolinone hybrid entities against the plasmodium species P. falciparum offered potent antimalarial molecules 6c, 6d, 6f, 6g, 6j & 6k owing comparable activity to the reference drugs. Furthermore, the target compounds were evaluated in vitro against Mycobacterium tuberculosis (MTB) H37Rv strain. Among the screened compounds, 6c, 6d and 6l were found to be the most active molecules with a MIC values of 19.57-40.68 µM. The cytotoxicity of the most active compounds was studied against RAW 264.7 cell line by MTT assay and no toxicity was observed. The computational study including drug likeness and ADMET profiling, DFT, and molecular docking study was done to explore the features of target molecules. The compounds 6a, 6g, and 6k exhibited highest binding affinity of -10.3 kcal/mol with docked molecular targets from M. tuberculosis. Molecular docking study indicates that all the molecules are binding to the falcipain 2 protease (PDB 6SSZ) of the P. falciparum. Our findings indicated that these new triazole-quinazolinone hybrids may be considered hit molecules for further optimization studies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plasmodium falciparum
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Triazoles
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Diseño de Fármacos
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Pruebas de Sensibilidad Microbiana
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Quinazolinonas
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Simulación del Acoplamiento Molecular
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Mycobacterium tuberculosis
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Antimaláricos
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Antituberculosos
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Reino Unido