Author/Authors :
Noushini, Saeedeh islamic azad university - Department of Chemistry, ايران , Alipour, Eskandar islamic azad university - Department of Chemistry, ايران , Emami, Saeed mazandaran university of medical sciences - Faculty of Pharmacy ,Research Center - Department of Medicinal Chemistry and Pharmaceutical Sciences, ايران , Safavi, Maliheh university of tehran - Institute of Biochemistry and Biophysics, تهران, ايران , Kabudanian Ardestani, Sussan university of tehran - Institute of Biochemistry and Biophysics, تهران, ايران , Gohari, Ahmad Reza tehran university of medical sciences tums - Medicinal Plants Research Center, تهران, ايران , Shafiee, Abbas tehran university of medical sciences tums - Faculty of Pharmacy and Pharmaceutical Sciences Research Center - Department ofMedicinal Chemistry, تهران, ايران , Foroumadi, Alireza tehran university of medical sciences tums - Medicinal Plants Research Center, Faculty of Pharmacy and Pharmaceutical Sciences Research Center - Department of Medicinal Chemistry, تهران, ايران
Abstract :
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 (IC50 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.
Keywords :
Synthesis , Chalcones , Cytotoxic activity , Cancer , Chroman , 4 , one
