Background: A wide range of thiazole, pyrazole and pyran derivatives gained special
attention due to pharmacological activities especially therapeutic activities. Many pharmacological
drugs containing the thiazole and pyrazole nuclei are known in the market.
Methods: The 2-arylidencyclohexan-1,3-dione 3a-c were the key starting compounds for many
heterocyclic reactions to produce substituted heterocyclic derivatives.
Results: Antiproliferative activities of the produced compounds against six cancer cell lines A549,
HT-29, MKN-45, U87MG, SMMC-7721 and H460 were measured in which the compounds showed
high inhibition. The most promising compounds were tested against tyrosine kinases (c-Kit, Flt-3,
VEGFR-2, EGFR, and PDGFR). Structure-Activity Relationship (SAR) was rationalized by
assessing the varying structural features of the molecules. In addition, the most active compounds
were selected for Pim-1 inhibition.
Conclusion: Thirty compounds were synthesized. Ten of them (3a, 3c, 5a, 5c, 7a, 10f, 11a, 13c, 16a
and 16c) were the most active compounds for selected cancer cell lines. Compounds 3c, 5c, 7a, 10f,
13c and 16c showed high inhibition toward the tyrosine kinases while compounds 3c, 5c and 10f
were the most potent to inhibit Pim-1.