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 ۳-benzylidenchroman-۴-ones were described as rigid chalcone analogues.   Materials and Methods: The reaction of resorcinol with ۳-chloropropionic acid in the presence of CF۳SO۳H was afforded corresponding propiophenone. It was cyclized using ۲M NaOH to give ۷-hydroxy-۴-chromanone. O-Alkylation of ۷-hydroxy-۴-chromanone with alkyl iodide in the presence of K۲CO۳ gave ۷-alkoxychroman-۴-one. Finally, condensation of chroman-۴-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 K۵۶۲ (human erythroleukemia), MDA-MB-۲۳۱ (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 ۴a containing ۷-hydroxy group on chromanone ring and ۳-bromo-۴-hydroxy-۵-methoxy substitution pattern on benzylidene moiety was the most potent compound with IC۵۰ values ≤ ۳.۸۶ μg/ml. It was ۶-۱۷ times more potent than etoposide against tested cell lines. Conclusion: We described synthesis and cytotoxic activity of poly-functionalized ۳-benzylidenechroman-۴-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.