Uses of -diketones for the synthesis of novel heterocyclic compounds and their antitumor evaluations

Abstract

The reaction of the 3-oxo-N,3-diphenylpropan-amide (3) with either malononitrile or ethyl cyanoacetate in ammonium acetate gave the 1,2-dihydropyridine derivatives 6a or 6b, respectively. On the other hand, carrying the same reaction in the presence of triethylamine gave the 1,6-dihydropyridine derivatives 7a and 7b, respectively. Moreover, compound 3 reacted with 2-aminoprop-1-ene-1,1,3-tricarbonitrile to give the pyridine derivative 9. Compound 7b reacted with the active methylene derivatives 10a,b and 4a,b to give the naphthyridine derivatives 11a,b and 12a,b; respectively. Compound 3 was also used for the synthesis of thiophene derivatives 13a,b and 16a,b. In addition, the reaction of ethyl benzoylacetate (1) with o-phenylene diamine gave the benzimidazole derivative 18. The reactivity of the latter product towards different reagents was studied to give different products. The cytotoxicity of the newly synthesized products was studied towards some cancer and normal cell lines, in addition toxicity of compounds was measured and docking of the most active compounds was done. Compounds 6b, 7b, 9, 13a, 13b, 16a, 20b, 20c, 24b, 25 and 26b exhibited optimal cytotoxic effect against cancer tested cell lines. These active compounds were evaluated against c-Met kinase using foretinib as the reference drug where all compounds expressed higher activity than the reference drug.

KEY WORDS: Ethyl benzoylacetate, Pyridine, Benzimidazole, Cytotoxicity

Bull. Chem. Soc. Ethiop. 2020, 34(2), 385-405

DOI: https://dx.doi.org/10.4314/bcse.v34i2.15