Synthesis, characterization and anti-tumor activity of moxifloxacin–Copper complexes against breast cancer cell lines

• Published in: Bioorganic & medicinal chemistry letters 2011-03, Vol.21 (6), p.1802-1806
• Main Authors: Patitungkho, Sommai, Adsule, Shreelekha, Dandawate, Prasad, Padhye, Subhash, Ahmad, Aamir, Sarkar, Fazlul H.
• Format: Article
• Language: English
• Subjects: anticarcinogenic activity; Antineoplastic agents; Apoptosis - drug effects; Aza Compounds - chemical synthesis; Aza Compounds - chemistry; Aza Compounds - pharmacology; Biological and medical sciences; Breast cancer; breast neoplasms; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation - drug effects; Copper - chemistry; Copper complexes; Drug Screening Assays, Antitumor; epithelial cells; Female; Fluoroquinolones; General aspects; Humans; Medical sciences; Moxifloxacin; nitrogen; Pharmacology. Drug treatments; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Spectrophotometry, Infrared
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.01.061

Novel moxifloxacin–copper complexes were synthesized, characterized and screened for anti-proliferative and apoptosis-inducing activity against hormone dependent (MCF-7 and T47D) and hormone independent (MDA-MB-231 and BT-20) breast cancer cell lines and was compared against non-tumorigenic breast epithelial cell line (MCF-10A). The results indicated that copper conjugate 2 and its nitrogen adducts 3– 5 exert significant growth inhibition of cancer cell lines and apoptosis-induction, compared to parent moxifloxacin ( 1) without any significant effect on non-tumorigenic MCF-10A cells. Interestingly, compound 5 was found to be very active against multiple cell lines. Novel moxifloxacin–copper complexes were synthesized, characterized and screened for anti-proliferative and apoptosis-inducing activity against multiple human breast cancer cell lines (hormone-dependent MCF-7 and T47D as well as hormone-independent MDA-MB-231 and BT-20). The results indicated that the parent compound moxifloxacin ( 1) does not exert any inhibitory activity against breast cancer cell lines examined. On the other hand, the copper conjugate 2 and its nitrogen adducts 3– 5 exerted growth inhibitory and apoptosis-inducing activity against breast cancer cell lines without any substantial effect on non-tumorigenic breast epithelial cells MCF-10A at equimolar concentration, suggesting a cancer cell-specific activity. BT-20 cells were more sensitive to compounds 2 and 3, while compounds 4 and 5 exerted significant anti-proliferative and apoptosis-inducing effects on T47D, MDA-MB-231 and BT-20 cell lines. Our results suggest that these novel compounds could be useful for the treatment of breast cancer in the future.