Thiazolo[4,5-d]pyridazine analogues as a new class of dihydrofolate reductase (DHFR) inhibitors: Synthesis, biological evaluation and molecular modeling study.

•Synthesis of 1,3-thiazoles and thiazolo[4,5-d]pyridazine analogues.•Compound 26 proved to be the most active DHFR inhibitor (IC50 of 0.06μM).•Compound 4, 20, 21 showed in vitro antitumor activity against a collection of cancer cell lines.•Compound 26 proved lethal to HS 578T breast cancer cell line with IC50 value of 0.8μM, inducing apoptotic cell cycle arrest.•Binding with Phe 31 and Arg 22 amino acids is essential for DHFR binding.