Synthesis of Heterocyclic Compounds Derived From Dimedone and Their Anti-tumor and Tyrosine Kinase Inhibitions

Abstract

The reaction of dimedone with arylaldehydes gave the benzylidene derivatives 3a–c, the latter underwent a series of heterocyclization reactions to give fused thiophene, pyrazole isoxazole and pyridazine derivatives. The synthesized compounds were evaluated against different kinds of cancer cell lines together tyrosine kinases and Pim-1 kinase inhibitions. All the synthesized compounds were assessed for the inhibitory activities against A549 (non-small cell lung cancer), H460 (human lung cancer), HT-29 (human colon cancer) and MKN-45 (human gastric cancer) cancer cell lines together with foretinib as the positive control by a MTT assay. The promising compounds were 3c, 5b, 5e, 5f, 7c, 7f, 9c, 11b, 12c, 12d, 13b, 13d, 14b, 16c and 16d among the tested compounds. On the other hand, compounds 5b, 5e, 5f, 7c, 11b, 12c, 12d, 13d, 14b, 16c and 16d were the most effective inhibitors against tyrosine kinases and compounds 5b, 11b, 12d, 13d, 14b and 16c were the most potent against Pim-1 kinase.

Keywords

• dimedone
• thiophene
• pyrazole
• isoxazole
• antitumor
• tyrosine kinase