One-pot synthesis of thiazolo[3,2-a]pyrimidine derivatives, their cytotoxic evaluation and molecular docking studies

An economical, simple and efficient one-pot method has been developed for the synthesis of thiazolo[3,2-a]pyrimidine hydrobromide derivatives. 2,4-diaryl-6,7,8,9-tetrahydro-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine hydrobromides were synthesized by the α-bromination of cyclohexanone with N-Bromosuccinamide (NBS) and followed by cyclization with 3,4-dihydropyrimidine-2(1H)-thiones, respectively, in the presence of p-toluenesulfonic acid (PTSA) in acetonitrile. However when cyclohexanone was replaced by acetyl acetone and alpha-tetralone gave the corresponding 1-(3-methyl-5,7-diaryl-5H-thiazolo[3,2-a]pyrimidin-2-yl)ethan-1-one hydrobromide and 9,11-diaryl-6,11-dihydro-5H-naphtho[1',2':4,5]thiazolo[3,2-a]pyrimidine hydrobromide derivatives, respectively. The significant features of this method are novel, simple, inexpensive experimental procedure, short reaction time, and good yield. The some of the synthesized compounds were evaluated for cytotoxic activity against human lung adenocarcinoma cell line (A549), human breast carcinoma cell line (MCF-7), human cervical cancer cell line (HeLa) and human neuronal carcinoma cell lines (SKNSH). Tested compounds 5(b-e) showed the excellent anticancer activity against various cell lines. Particularly compound 5c with IC₅₀ value of 2.2 ± 0.6 μM against A549 and compound 5e with IC₅₀ value of 5.6 ± 0.4 μM against HeLa showed best cytotoxic effects. Furthermore, Molecular docking study was performed for some of the synthesized compounds 5(b-e) against topoisomerase-II by using Auto dock method. Docking results of the compounds 5c, 5d, and 5e exhibited higher cytotoxic activity than the standard doxorubicin.