Design, synthesis, and cytotoxic activity of some novel N-(substituted) benzamide derivatives bearing coumarin and 1-azocoumarin compounds

ABSTRACT. Among oxygen-containing heterocyclic compounds such as coumarin and azacoumarin derivatives, the scaffold has become an important construction motif for developing new drugs. Coumarin its derivatives possess many types of biological activities have been reported to show significant cytotoxic activity. N-(6,8-disubstituted coumarin-3-yl)benzamides (8a-c) namely (3-N-(benzoyl) aminocoumarin-6-ylmethyl acetate (8a); N-[6-(1-acetylpyrazol-3-yldiazineyl) coumarin-3-yl] benzamide (8b); N-(8-methoxy-6-bromo-coumarin-3-yl) (8c), were synthesized via a cyclocondensation reaction 5-(chloromethyl)-2-hydroxybenzaldehyde (3), 5-(pyrazol-3-yl-diazineyl)-2-hydroxybenzaldehyde (4), 5-bromo-3-methoxy- 2-hydroxybenzaldehyde (5) with N-benzoylglycine (7), in good yield. Treatment compound 8c ammonia presence anhydrous potassium carbonate yield N-(5-bromo-8-methoxy-1-azocoumarin-3-yl) (9). Compound (9) was acetylated acetic anhydride give N-(2-acetoxy-5-bromo-8-methoxyquinolin-3-yl) (10). N-(substituted azacoumarin-3-yl) benzamides (8-10) tested their vitro activity against (HepG2) cell line. Furthermore, DNA flow cytometry investigation over HepG2 cells indicated that 8a demonstrated arrest at G1/S stages cycle induction apoptosis by rising pre-G1 stage. displayed tubulin polymerization inhibition.
 
 KEY WORDS: Synthesis, Coumarin, Azacoumarin, Drugs, Cytotoxicity
 Bull. Chem. Soc. Ethiop. 2023, 37(4), 1003-1019. DOI: https://dx.doi.org/10.4314/bcse.v37i4.16