Background: Recently multi-component reactions producing pyran and pyridine derivatives acquired a
special attention due to their wide range of pharmacological activities, especially therapeutic activities. Through
the market, it was found that many pharmacological drugs containing the pyran and pyridine nucleus were
Objective: We are aiming in this work to synthesize target molecules possess not only anti-tumor activities but
also kinase inhibitors. The target molecules were obtained starting from cyclohexane-1,3-dione followed by its
heterocyclization reactions to produce anticancer target molecules.
Methods: This work demonstrated multi-component reactions of cyclohexan-1,3-dione with aromatic aldehydes
and diethylmalonate using triethylamine as a catalyst to give the 7,8-dihydro-4H-chromen-5(6H)-one derivatives
4a-c. The reaction of compounds 4a-c with either of hydrazine hydrate of phenylhydrazine gave the
chromeno[2,3-c]pyrazole derivatives 5a-f, respectively. In addition, further heterocyclization reactions were
adopted to give the chromeno[3,2-d]isoxazole, chromene-3-carboxamide derivatives. Moreover, the multicomponent
reaction of cyclohexan-1,3-dione (1) with either of aromatic aldehydes and diethylmalonate using a
catalytic amount of ammonium acetate gave the 1,4,5,6,7,8-hexahydroquinoline derivatives 13a-c. The antiproliferative
activities of the synthesized compounds toward the six cancer cell lines namely A549, H460, HT-
29, MKN-45, U87MG, and SMMC-7721 were studied. In addition, the c-Met enzymatic activities and inhibition
toward the prostate cancer cell PC-3 were measured.
Results: Anti-proliferative evaluations, c-Met enzymatic activities and inhibition toward the prostate cancer cell
PC-3 were measured, and the results obtained in most cases indicated that the presence of electronegative Cl
group through the molecule favour the inhibitions.
Conclusion: The compounds with high anti-proliferative activity towards the cancer cell lines were 4a, 4b, 6d,
6e, 6f, 10e, 10f, 12c, 14e, 14f, 15c, 16d, 16e, 16f, 19c and 20c. Compounds 4b, 6c, 6d, 8b, 10c, 10d, 12b, 13b,
14c, 14d, 15b, 16c, 16d, 17b, 17c, 19b, 20b and 20c exhibited high potency against c-Met kinase and
compounds 4a, 4b, 6b, 6c, 6d, 6f, 8b, 8c, 10c, 10d, 10e, 12b, 12c, 13a, 13b, 13c, 14c, 14d, 14e, 14f, 15b, 15c,
16b, 16c, 16d, 17b, 17c, 19c, 19d, 20a, 20b and 20c displayed high inhibitions toward PC-3 cell line.