Synthesis and anticancer activity of newthiazolo [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 H-1 NMR, (CC)-C-13 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, nonsmall 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 GI(50), 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 39 in vitro to their abilities to bind at DNA minor groove. (C) 2017 Elsevier Inc. All rights reserved.