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

• Published in: Iranian journal of basic medical sciences Vol. 16; no. 11; pp. 1155 - 1162
• Main Authors: Letafat, Bahram, Shakeri, Raheleh, Emami, Saeed, Noushini, Saeedeh, Mohammadhosseini, Negar, Shirkavand, Nayyereh, Kabudanian Ardestani, Sussan, Safavi, Maliheh, Samadizadeh, Marjaneh, Letafat, Aida, Sha Ee, Abbas, Foroumadi, Alireza
• Format: Journal Article
• Language: English
• Published: Iran Mashhad University of Medical Sciences 01-11-2013
• Subjects: Chalcones Cytotoxic activity 4-Chromanone Synthesis; Original; Chalcones; Synthesis; 4-Chromanone; Cytotoxic activity
• ISSN: 2008-3866; 2008-3874

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.
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.
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.
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.