Synthesis and cytotoxicity of nitrogen‐containing curcuminoids against cancer cell lines

Abstract

AbstractIn a previous study, we performed the structural modification of the curcumin skeleton by varying substituents in phenyl rings. In continuation of that work, we now focus on the synthesis of nitrogen‐containing curcuminoids by a pyrazole cyclization between the free β‐diketone curcuminoids bearing ‐OCH3/‐OH/‐F substituents in aromatic rings and phenyl hydrazine hydrochloride. Seven N‐phenyl pyrazole curcuminoids (1a‐7a) were synthesized in yields of 39‐73 % and derivative (7a) was reported for the first time. Synthesized compounds were evaluated for their cytotoxicities against HepG2, LU‐1 and KB cancer cell lines. Compared to the pristine compound, i.e., curcumin, compound (1a) demonstrated better inhibitory activities toward three cell lines. Derivative (2a) exhibited higher anti‐cancer capacity against HepG2 and LU‐1 than curcumin. Analogues (4a‐7a) bearing pyrazole ring and ‐OCH3/‐F groups in aromatic rings displayed low/inactive anti‐cancer activities. In addition, compared to pyrazole curcumin (PC), derivative (1a) containing N‐phenyl substituent displayed lower cytotoxicities toward HepG2 and KB cell lines.