Acta Pharm. 65 (2015) 53-63

 

full paper

Original research paper

 

Potential antiproliferative effect of isoxazolo- and thiazolo coumarin derivatives on breast cancer mediated bone and lung metastases

LULZIME BALLAZHI, EMIL POPOVSKI, AHMED JASHARI, FAIK IMERI, IBRAHIM IBRAHIMI, BOZHANA MIKHOVA and KRISTINA MLADENOVSKA

krml@ff.ukim.edu.mk

1 Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University “Ss. Cyril and Methodius”, 1000 Skopje, Republic of Macedonia

2 Institute of Chemistry, Faculty of Natural Sciences & Mathematics, University “Ss. Cyril & Methodius”, PO Box 162, 1000 Skopje, Republic of Macedonia

3 Faculty of Natural Sciences & Mathematics, State University of Tetovo, 1200 Tetovo, Republic of Macedonia

4 Institute of Pharmacology, University of Bern, CH-3010 Bern, Switzerland

5 Faculty of Medical Sciences, State University of Tetovo, 1200 Tetovo, Republic of Macedonia

6 Institute of Organic Chemistry with Centre of Phytochemistry Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria

Accepted October 13, 2014

 

The study highlights the current progress in the development of coumarin scaffolds for drug discovery as novel anticancer agents in metastatic breast cancer. Eight  compounds, combining the coumarin core and five membered heterocycles (isoxazoles and thiazoles) in hydrazinyldiene-chroman-2,4-diones, were characterized in terms of a potential antiproliferative effect on bone (SCP1833) and lung (SCP4175) metastatic breast cancer cell lines using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Cell viability was evaluated after 48 and 72 h of treatment and the 50 % inhibitory concentrations were determined. The results demonstrated dose- and time-dependent activity, with the most potent molecules having a thiazole moiety, without or with additional methyl group(s) attached to the carbon(s) at position(s) 5 and/or 4 in the thiazole ring. These molecules possessed significantly higher potency against both test cell lines compared to 4-hydroxycoumarin.

 

Keywords: chromandiones, breast cancer, metastatic cells, antiproliferative effect