New Indole-6-Carboxylic Acid Derivatives as Multi-Target Antiproliferative Agents: Synthesis, in Silico Studies, and Cytotoxicity Evaluation.
Chem Biodivers
; 21(2): e202301892, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38145305
ABSTRACT
Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are commonly overexpressed in cancers making them appealing targets for cancer therapeutics. Two groups of indole-6-carboxylic acid derivatives, hydrazone derivatives targeting EGFR and oxadiazole derivatives targeting VEGFR-2, were synthesized and characterized using FT-IR, 1 H-NMR, 13 CNMR, and HR-MS techniques. Binding patterns to potential molecular targets were studied using molecular docking and compared to standard EGFR and VEGFR-2 inhibitors. The newly synthesized compounds were cytotoxic to the three cancer cell lines tested (HCT-116, HeLa, and HT-29â
cell lines) as evaluated by the MTT assay. Compoundâ
3 b (EGFR-targeting) and compoundâ
6 e (VEGFR-2-targeting) possessed the highest antiproliferation activity, were cancer-selective, arrested cancer cells in the G2/M phase, induced the extrinsic apoptosis pathway, and had the highest EGFR/VEGFR-2 enzyme inhibitory activity, respectively. The structure-activity relationships of the new compounds showed that the presence of an aryl or heteroaryl fragment attached to a linker is required for the anti-tumor activity. In conclusion, the findings of the current study suggest that compoundsâ
3 b and 6 e are promising cytotoxic agents that act by inhibiting EGFR and VEGFR-2 tyrosine kinases, respectively.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptor 2 de Fatores de Crescimento do Endotélio Vascular
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Chem Biodivers
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Iraque