synthesis and in vitro cytotoxic activity of novel chalcone-like agents

objective(s): chalcones and their rigid analogues represent an important class of small molecules having anticancer activities. therefore, in this study the synthesis and cytotoxic activity of new 3-benzylidenchroman-4-ones were described as rigid chalcone analogues.   materials and methods: the reaction of resorcinol with 3-chloropropionic acid in the presence of cf3so3h was afforded corresponding propiophenone. it was cyclized using 2m naoh to give 7-hydroxy-4-chromanone. o-alkylation of 7-hydroxy-4-chromanone with alkyl iodide in the presence of k2co3 gave 7-alkoxychroman-4-one. finally, condensation of chroman-4-one derivatives with different aldehydes afforded target compounds in good yields. the newly synthesized compounds were tested in vitro against different human cancer cell lines including k562 (human erythroleukemia), mda-mb-231 (human breast cancer), and sk-n-mc (human neuroblastoma) cells. the cell viability was evaluated using mtt colorimetric assay. results: most of the compounds showed good inhibitory activity against cancer cells. among them, compound 4a containing 7-hydroxy group on chromanone ring and 3-bromo-4-hydroxy-5-methoxy substitution pattern on benzylidene moiety was the most potent compound with ic50 values ≤ 3.86 μg/ml. it was 6-17 times more potent than etoposide against tested cell lines. conclusion: we described synthesis and cytotoxic activity of poly-functionalized 3-benzylidenechroman-4-ones as new chalcone-like agents. these compounds can be considered as conformationally constrained congeners of chalcones to tolerate the poly-functionalization on the core structures for further optimization.