Multi-component reactions of cyclohexan-1,3-dione to synthesize heterocyclic derivatives with c-Met enzymatic activity, anti-prostate, anti-proliferative and tyrosine kinase activities

Abstract

ABSTRACT. We are aiming in this work to synthesize target molecules not only possess anti-tumor activities but also kinase inhibitors. The target molecules were obtained starting from aryl hydrazones of cyclohexan-1,3-dione  followed by its heterocyclization reactions to produce anticancer molecules. The multi-component reactions of the arylhydrazocyclohexan-1,3-dione derivatives 3a-c produced the 1,4,5,6,7,8-hexahydroquinoline derivatives 6a-r and the 4,5,6,8-tetrahydrochromeno[2,3-c]pyrazole derivatives 10a-c. Other multi-component reactions were demonstrated. The anti-proliferative activity of the synthesized compounds toward the six cancer cell lines namely A549, H460, HT-29, MKN-45, U87MG, and SMMC-7721 was studied. In addition the c-Met enzymatic activities and inhibition toward the prostate cancer cell PC-3 were measured. The results obtained in most cases, indicated that the presence of electronegative Cl group through the molecule favour the inhibitions.

KEY WORDS: Multi-component reactions, Cyclohexan-1,3-dione, Chromene, Chromeno[2,3-c]pyrazole, Cytotoxicity

Bull. Chem. Soc. Ethiop. 2022, 36(1), 119-136.                                                            

DOI: https://dx.doi.org/10.4314/bcse.v36i1.11