Synthesis and biological evaluation of coumarine-imidazo[1,2-c][1,2,3] triazoles: PEG-400 mediated one-pot reaction under ultrasonic irradiation

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 and absence of ultrasound, the [3 + 2] cycloaddition followed by C-N bond formation reaction be-tween 3-(iodoethynyl)-2H-chromen-2-one and substituted 2-chloro-N-phenylacetamides was carried out under relatively optimized conditions. The cancer activity of the synthesized compounds were then tested in vitro against two MCF-7 and A-549 and the majority of the examined compounds 4e-4o showed significant activity, with compounds 4f, 4 g, and 4 h surpassing the standard drug against the A-549 line, and 4 m and 4n excelling it against MCF-7. Later, in vitro EGFR results revealed that compounds 4f (IC50 = 0.420 & PLUSMN; 0.08 & mu;M), 4 g (IC50 = 0.367 & PLUSMN; 0.02 & mu;M), and 4 h (IC50 = 0.453 & PLUSMN; 0.02 & mu;M) were more effective than the conventional medicine Erlotinib (IC50 = 0.460 & PLUSMN;0.06 & mu;M). In silico investigations of more potent compounds (4f, 4 g, 4 h, 4i, 4k, 4 m, and 4n) and erlotinib on the EGFR protein indicated that all seven compounds had much higher binding energies and inhibition constants than the erlotinib. Finally, the in silico pharmacokinetic profile of compounds 4f, 4 g, 4 h, 4i, 4k, 4 m, and 4n was estimated using SWISS/ADME and pkCSM, where all compounds followed Lipinski, Veber, Egan, and Muegge rules without deviation.

Automated summary

Synthetic chemists have developed effective methods for perfect synthesis to meet the demand for crucial scaffolds in medical applications. The synthesis of fused 1,2,3-triazoles was investigated in the presence and absence of ultrasound, resulting in the discovery of several compounds with significant cancer activity. In vitro testing showed that compounds 4f, 4g, and 4h were more effective against EGFR than the standard drug Erlotinib.