Synthesis and cytotoxic properties of novel (E)-3-benzylidene-7-methoxychroman-4-one derivatives

• Published in: Daru Vol. 21; no. 1; p. 31
• Main Authors: Noushini, Saeedeh, Alipour, Eskandar, Emami, Saeed, Safavi, Maliheh, Ardestani, Sussan Kabudanian, Gohari, Ahmad Reza, Shafiee, Abbas, Foroumadi, Alireza
• Format: Journal Article
• Language: English
• Published: London BioMed Central 12-04-2013; BioMed Central Ltd
• Subjects: Acetates - pharmacology; Acetic acid; Aldehydes; Antineoplastic Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Cancer; Cell Line, Tumor; Cell Proliferation - drug effects; Chemotherapy; Humans; Isoflavones - chemical synthesis; Isoflavones - pharmacology; Medicinal Chemistry; Organic acids; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Pyrazoles - pharmacology; Research Article; Structure-Activity Relationship; Chalcones; Synthesis; Chroman-4-one; Cytotoxic activity; Cancer
• ISSN: 1560-8115; 2008-2231; 2008-2231
• DOI: 10.1186/2008-2231-21-31

Background and the purpose of the study
There has been increscent interest in the field of cancer chemotherapy by discovery and development of novel agents with high efficacy, low toxicity, and minimum side effects. In order to find new anticancer agents, we replaced the pyrazolone part of well-known cytotoxic agent SJ-172550 with 7-methoxychroman-4-one. Thus, a novel series of 3-benzylidene-4-chromanones were synthesized and tested in vitro against human cancer cell lines.
Methods
The title compounds were prepared by condensation of 7-methoxychroman-4-one with suitable aldehydes in appropriate alcohol in the presence of gaseous HCl. The antiproliferative activity of target compounds were evaluated against MDA-MB-231 (breast cancer), KB (nasopharyngeal epidermoid carcinoma) and SK-N-MC (human neuroblastoma) cell lines using MTT assay.
Results
Although the direct analog of SJ-172550 (compound
5d
) did not show any cytotoxic activity against tested cell lines, but 2-(2-chloro-6-methoxyphenoxy)acetic acid methyl ester analog
5c
showed some activity against MDA-MB-231 and SK-N-MC cells. Further modification of compound
5c
resulted in the 3-chloro-4,5-dimethoxybenzylidene derivative
5b
which demonstrated better cytotoxic profile against all tested cell lines (IC
50
values = 7.56–25.04 μg/ml).
Conclusion
The results demonstrated that the cytotoxic activity of compound
5b
against MDA-MB-231 and SK-N-MC cells is more than etoposide. Therefore, compound
5b
prototype could be considered as novel cytotoxic agent for further developing new anticancer chemotherapeutics.