Cytotoxic Effects of Diclofenac and Ibuprofen Zinc (II)-Nicotinamide Ternary Complexes in Breast Cancer Cell Lines

HIGHLIGHTS

Diclofenac and ibuprofen-derived complexes decrease viability of breast cancer cell lines

Complex 1 presented antitumor effect in all breast cancer cell lines tested including on triple negative cell line (MDA-MB-231) (IC50 202µM)

Complex 1 was selective for both 4T1 and MDA-MB-231 cells

Abstract

Breast cancer is one of the leading types of cancer worldwide, and the search for new treatment options are crucial. Nonsteroidal anti-inflammatory drugs (NSAIDs) -specially ibuprofen and diclofenac-, have shown antitumoral effect against several types of cancer. The synthesis of organometallic compounds has shown significant improvements in pharmacological properties and efficacy of organic molecules. Two zinc II ternary complexes containing the NSAIDs diclofenac and ibuprofen and nicotinamide neutral linker (Nic) were obtained by the two-step solvent metalligand complexation method. The compounds Zn₂(Diclof)₄(Nic)₂ (complex 1) and Zn₂(Ibup)₄(Nic)₂ (complex 2) were tested in breast cancer cell lines (4T1, MCF-7 and MDA-MB-231) to evaluate their cytotoxicity, comparing to ibuprofen and diclofenac as controls. We found that both complex 1 and 2 exerted more than 60% reduction in 4T1 viability at 250µM, and complex 2 decreased cell viability at 250 µM and 137.5 µM in MCF-7 (34.35% and 26.42% reduction, respectively) and in MDA-MB-231 (57.2% and 22.88% reduction, respectively), all compared to controls. Complex 1 was selective only in MCF-7, and complex 2 was selective in both MCF-7 and MDA-MB-231. In summary, our data showed that the cytotoxic effect of complex 1 and 2 is increased comparing to their original NSAID in different breast cancer cell lines, highlighting their potential anti-tumoral activity.

Keywords:
NSAIDs; Zinc complexes; cytotoxicity; coordination compounds; cell viability