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Iran J Basic Med Sci. 2013 Nov;16(11):1155-62.

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

Author information

1
Department of Chemistry, Central Tehran-Branch, Islamic Azad University, Tehran, Iran.
2
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
3
Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
4
Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
5
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran ; Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
6
Department of Chemistry, Tabriz Branch, Islamic Azad University, Tabriz, Iran.

Abstract

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.

KEYWORDS:

4-Chromanone; Chalcones; Cytotoxic activity; Synthesis

PMID:
24494068
PMCID:
PMC3909627

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