Heterocyclization of Thiophenes derived from Estrone followed by cytotoxic, HTRF kinase and Pim-1 kinase evaluations.

BACKGROUND: Among wide range of heterocyclic steroidal derivatives acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs containing the steroid nucleus were known in the market.

OBJECTIVE: Our main aim of this work was to synthesis a seies of heterocyclic compounds especially thiophene and thienopyridine derivatives containing the estrone nucleuous. The synthesized compounds possising antitumor and kinases inhibitions.

METHOD: Thiophene derivatives of estrone were synthesized and used for further heterocyclization reactions through the reaction with different reagent.

RESULTS: Antiproliferative evaluations and c-Met kinase, Pim-1 kinse inhibitions were performed where some compounds revealed high activities.

CONCLUSION: Compounds that showed high antiprolifeative activity and c-Met- kinase inhibitions were tested for all compounds. The most promising compounds 3b, 5c, 6c, 8d, 8f, 13e, 13f, 18b and 20d were further investigated against tyrosin kinase (c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR). Compounds 6b, 13b, 16b and 16c were selected to examine their Pim-1 kinase inhibition activity where compounds 11c, 18b and 20f showed high activities. Structure-activity relationship (SAR) was rationalized by looking at the varying structural features of the molecules.