Design and Synthesis of 2-Phenylindolizine Acetamides: Molecular Docking, in Vitro Antimicrobial and Anticancer Activity Evaluation.
Chem Biodivers
; 21(5): e202400075, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38466656
ABSTRACT
In the present work, we synthesized a small library of 2-phenylindolizine acetamide derivatives 7a-i and studied their biological activity. The synthesis was accomplished starting with easily available starting material phenacyl bromide 1 proceeding through the key intermediate 6-methyl-7-nitro-2-phenylindolizine 4. All the compounds 7a-i were characterized using spectroscopy viz., 1H-NMR, 13C NMR, FTIR, and mass spectrometry. Interestingly, 2-phenylindolizine scaffolds 7c, 7f and 7g revealed a remarkable antibacterial activity against relevant organisms S. aureus, E. coli, S. pneumoniae, P. aeruginosa. The target compounds 7e and 7h showed excellent anticancer activity against Colo-205 and MDA-MB-231â
cell lines with IC50 values of 68.62, 62.91, 54.23 and 46.34â
µM respectively. Additionally, all the 2-phenylindolizine acetamide derivatives 7a-i were subjected to molecular docking prediction by Autodock 4.2. Compounds 7a, 7f and 7c exhibited very good hydrogen bonding amino acid interactions Asp83 (2.23â
Å), Asp83 (2.08â
Å), His74 (2.05â
Å), His76 (1.71â
Å), Ser80 (1.05â
Å) with active site of Topoisomerase-IV from S. pneumoniae (4KPE). Further, the compounds 7a-i have revealed acceptable ranges for drug-likeliness properties upon evaluation using SwissADME for ADMET and physiochemical properties.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ensaios de Seleção de Medicamentos Antitumorais
/
Desenho de Fármacos
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Testes de Sensibilidade Microbiana
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Simulação de Acoplamento Molecular
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Indolizinas
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Acetamidas
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Chem Biodivers
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Índia
País de publicação:
Suíça