Copper-tolfenamic acid: evaluation of stability and anti-cancer activity.

Abstract

The non-steroidal anti-inflammatory drug, Tolfenamic acid (TA) acts as an anti-cancer agent in several adult and pediatric cancer models. Copper (Cu) is an important element with multiple biological functions and has gained interest in medical applications. Recently, [Cu(TA)2(bpy)] (Cu-TA) has been synthesized in order to enhance therapeutic activity. In this study, we synthesized Cu-TA using an established method, characterized it by UV visible spectroscopy and Fourier-transform infrared spectroscopy (FTIR), and tested its anti-cancer activity using twelve cell lines representing various cancers, such as Ewing sarcoma, glioblastoma, medulloblastoma, neuroblastoma, pancreatic and prostate. The anti-proliferative activity of Cu-TA was determined at 48 h post-treatment and compared with the parental compound, TA. The IC50 values were calculated using GraphPad Prism software. The biological stability of Cu-TA was evaluated using twelve-month-old powder and six-month-old stock solution. Cardiomyocytes (H9C2) were used to test the cytotoxicity in non-malignant cells. Cu-TA showed higher anti-proliferative activity, and the IC50 values were 30 to 80% lower when compared with TA. H9C2 cells were non-responsive to Cu-TA, suggesting that it is selective towards malignant cells. Comparison of the twelve-month-old powder and six-month-old stock solution using the Panc1 cell line showed similar IC50 values (<5% variation), confirming the stability of Cu-TA either in powder or solution form. These findings demonstrate the potential of Cu-TA as an effective anti-cancer agent. Further studies to delineate the detailed mechanism of action of Cu-TA for specific cancer model are underway.

• Authors: Myrna Hurtado, Umesh T Sankpal, Jaya Chhabra, Deondra T Brown, Rajasekhar Maram, Rafid Patel, Raj K Gurung, Jerry Simecka, Alvin A Holder, Riyaz Basha
• Journal: Investigational new drugs (Invest New Drugs) Vol. 37 Issue 1 Pg. 27-34 (02 2019) ISSN: 1573-0646 [Electronic] United States
• PMID: 29761244 (Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antineoplastic Agents
• ortho-Aminobenzoates
• tolfenamic acid
• Copper

Topics

• Anti-Inflammatory Agents, Non-Steroidal (chemistry, pharmacology)
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Copper (chemistry)
• Humans
• Neoplasms (drug therapy, pathology)
• Tumor Cells, Cultured
• ortho-Aminobenzoates (chemistry, pharmacology)