Synthesis and molecular docking study of n-alkyl/aryl-2-aryl indol-3-yl glyoxylamides as novel anticancer agents

摘要

Objective: To synthesize structurally distinct N-alkyl/aryl-2-aryl indol-3yl-glyoxylamides to evaluate their anticancer activity on Murine double minutes-2(MDM2) receptor bind p53 and Pheripheral benzodiazepine receptor (PBR) protein. Methods: A series of new appropriately N-alkyl/aryl-2-aryl indol-3-yl glyoxylamides (2a-h), were synthesized by the reaction of 2-arylindoles, oxalyl chloride and different amines in one pot reaction. Structure of all the new compounds were elucidated by spectral analysis and evaluated in silico docking study with MDM2 receptor bind p53 and PBR protein. Results: Among all the tested compounds, the 2-[2-(4-chlorophenyl)-1H-indol-3-yl]-2-oxo-N-propylacetamide (2e) showed high binding affinity on MDM2 receptor bind p53 protein. While remaining, the 2-(5-chloro-2-phenyl-1H-indol-3-yl)-N-(2,4-dimethylphenyl)-2-oxoacetamide (2a), N-(4-fluorophenyl)-2-[2-(4-methylphenyl)-1H-indol-3-yl]-2-oxoacetamide (2b) and 2-[2-(4-methylphenyl)-1H-indol-3-yl]-2-oxoacetamide (2c) were shown comparably good binding affinity on PBR protein. Conclusion: The Docking study of newly synthesized compounds revealed that the N-alkyl/aryl-2-aryl indol-3yl-glyoxylamides could be a very useful scaffold for anticancer therapy particularly on MDM2 receptor bind p53 and PBR protein.