New thiazolopyrimidine as anticancer agents: Synthesis, biological evaluation, DNA binding, molecular modeling and ADMET study

[Display omitted] •New series of thiazolopyrimidine derivatives has been synthesized.•Antitumor screening according to NCI protocol against 60 different cell lines has been performed.•DNA binding affinity of the synthesized compounds has been calculated.•Predicted ADMET data for the target compounds were also estimated.•Molecular modeling study has been conducted. In the present study, new series of thiazolopyrimidine derivatives was synthesized as purine analogs. The structures of the products were confirmed through spectroscopic techniques such as NMR and mass spectrometry. In addition, the synthesized compounds were evaluated as antitumor active agent through NCI screening protocol against 60 different cell lines under 9 different panels. Furthermore, DNA binding activity of the compounds was also evaluated. The results revealed that compound 35 proved to be the most active member of the tested series and it is promoted to the 5-dose testing where it gives GI50, TGI and LC50 values of 1.07, 6.61, 34.7 μM respectively. Furthermore, it also proved to have a good DNA binding activity with value that is comparable with that produced by doxorubicin which was used as positive standard. In addition, compound 27 was proved to be the most active DNA binding agent with binding affinity 28.38 ± 1.1. The pharmacokinetic properties were also calculated. Molecular docking studies suggested binding mode of compounds 27 and 35 to DNA minor groove via hydrogen bonding interaction. The anticancer activity of compounds 27 and 35 may be attributed to DNA binding.