Synthesis and anticancer activity of new thiazolo[3,2-a]pyrimidines: DNA binding and molecular modeling study

A novel series of nitrogenous heterocycles starting from chalcones including thiazolo[3,2-a]pyrimidines (20-67), were synthesized. Structure elucidation of the synthesized compounds was attained by the use of ¹H NMR, ¹³CC NMR, and Mass spectrometry. The obtained compounds were evaluated for their in vitro anticancer activity at the National Cancer Institute (NCI) 60 cell lines panel assay. Three cell lines, non-small cell lung cancer Hop-92, ovarian cancer IGROV1, and melanoma SK-MEL-2, exhibited some sensitivity against most of the tested compounds. Six compounds have passed the 5-log dose level NCI assay. Compounds 34 and 24 proved to be the most active derivatives with GI₅₀, TGI, LC₅₀ of 5.89, 20.0, 66.1% and 5.0, 19.5, 52.5% respectively. Compounds 36, 39, 63 showed lesser activity with GI₅₀, TGI, LC₅₀ 3.2, 11.8, 38.9%, 3.4, 16.6, 60.3%, 3.5, 17.8, 66.1% respectively. DNA binding assay of synthesized compound were performed. Molecular docking showed that compounds 34, 42, and 60 could effectively fit into the minor groove and selectively bind with AT base pairs. The results could confer the anticancer activity of compounds 24, 34, 36, and 39in vitro to their abilities to bind at DNA minor groove.