Ultrasound-assisted synthesis of novel 2-aryl-3-ethoxy-5-methyl-3-oxido-2H-thiazolo[2,3-e][1,4,2]diazaphosphole-6-carboxylates and their anticancer efficacy in inducing apoptosis and autophagy and targeting cell cycle progression†

Abstract

A novel class of ethyl 2-aryl-3-ethoxy-5-methyl-3-oxido-2H-thiazolo[2,3-e][1,4,2]diazaphosphole-6-carboxylates (2a–j) were synthesized via a one-pot, three-component method. This reaction utilized ethyl 2-amino-4-methylthiazole-5-carboxylate (1) with different aromatic aldehydes and ethyl dichlorophosphite in THF under ultrasonic irradiation, with triethylamine as an efficient catalyst at 50 °C. The reaction provided the desired products 2a–j in high yields within a short timeframe. The cytotoxic effects of the synthesized compounds were assessed against two human cancer cell lines, lung cancer (A549) and renal cancer (TK-10), using the sulforhodamine B (SRB) assay. This evaluation revealed that products 2e, 2h and 2j demonstrated significantly higher cytotoxicity against the studied cancer cells than the standard drug doxorubicin. These bioactive products notably increased the late apoptosis rate in both cell lines and demonstrated a promising high ability to arrest the cell cycle at different phases in renal TK-10 and lung A549 cancer cells. Additionally, compounds 2e, 2h and 2j displayed potential for inducing autophagy.