Gold(I) Complexes Based on Nonsteroidal Anti-Inflammatory Derivatives as Multi-Target Drugs against Colon Cancer
Javier Sáez, Javier Quero, María Jesús Rodriguez‐Yoldi, M. Concepción Gimeno, Elena Cerrada
Abstract
High Resolution Image Download MS PowerPoint Slide Targeting inflammation and the molecules involved in the inflammatory process could be an effective cancer prevention and therapy strategy. Therefore, the use of anti-inflammatory strategies, such as NSAIDs and metal-based drugs, has become a promising approach for preventing and treating cancer by targeting multiple pathways involved in tumor progression. The present work describes new phosphane gold(I) complexes derived from nonsteroidal anti-inflammatory drugs as multitarget drugs against colon cancer. The antiproliferative effect of the most active complexes, [Au(L3)(JohnPhos)] ( 3b ), [Au(L4)(CyJohnPhos)] ( 4a ) and [Au(L4)(JohnPhos)] ( 4b ) against colon cancer cells (Caco2-/TC7) seems to be mediated by the inhibition of the enzyme cyclooxygenase-1/2, modulation of reactive oxygen species levels by targeting thioredoxin reductase (TrxR) activity, and induction of apoptosis in cancer cells. Additionally, the three complexes exhibit high selectivity index values toward noncancerous cells. The research highlights the importance of maintaining cellular redox balance and the role of TrxR in cancer cell survival.