Synthesis and anti-breast cancer evaluation of fused imidazole-imidazo[1,2-c][1,2,3]triazoles: PEG-400 mediated one-pot reaction under ultrasonic irradiation

Abstract

Synthetic chemists have organized easy and effective ways for perfect synthesis in response to the requirement for scaffolds that are crucial for medical applications. To investigate the synthesis of fused 1,2,3-triazoles in the presence of ultrasound, the [3 + 2] cycloaddition followed by CN bond formation reaction between 2-chloro-N-(1-methyl-1H-imidazol-2-yl)acetamide and substituted aryl iodoalkynes was carried out ourpreviously reported condition. The cancer activity of the synthesized compounds were then tested in vitro against two breast cancer cell lines MCF-7 and MDA-MB231 and some of the compounds 5g and 5j showed more potent activity against MCF-7 compared to standard erlotinib (IC50 = 4.70 ± 0.11 μM) with IC50 values 4.02 ± 0.74 and 4.23 ± 0.65 μM. Later, in vitro EGFR results revealed that compound 5g (IC50 = 0.38 ± 0.02 μM) have shown more effective than the conventional medicine erlotinib (IC50 = 0.42 ± 0.04 μM). Compounds 5j (IC50 = 0.42 ± 0.05 μM) have shown equipotent, 5i (IC50 = 0.53 ± 0.02 μM) and 5k (IC50 = 0.58 ± 0.02 μM) were shown good activity compared to the standard erlotinib. In silico investigations of more potent compounds (5g, 5i, 5j, 5k, and 5q) and erlotinib on the EGFR protein indicated that all five compounds had comparable binding energies and inhibition constants than the erlotinib.