Selenylated Imidazo [1,2-a]pyridine Induces Apoptosis and Oxidative Stress in 2D and 3D Models of Colon Cancer Cells

Abstract

Colon cancer incidence rates are increasing annually, a scenario aggravated by genetic and epigenetic alterations that promote drug resistance. Recent studies showed that novel synthetic selenium compounds are more efficient and less toxic than conventional drugs, demonstrating biocompatibility and pro-oxidant effects on tumor cells. This study aimed to investigate the cytotoxic effect of MRK-107, an imidazo [1,2- a]pyridine derivative, in 2D and 3D cell culture models of colon cancer (Caco-2 and HT-29). Sulforhodamine B results revealed a GI50 of 2.4 µM for Caco-2, 1.1 µM for HT-29, and 22.19 µM for NIH/3T3 in 2D cultures after 48 h of treatment. Cell recovery, migration, clonogenic, and Ki-67 results corroborated that MRK-107 inhibits cell proliferation and prevents cell regeneration and metastatic transition by selectively reducing migratory and clonogenic capacity; non-tumor cells (NIH/3T3) re-established proliferation in less than 18 h. The oxidative stress markers DCFH-DA and TBARS revealed increased ROS generation and oxidative damage. Caspases-3/7 are activated and induce apoptosis as the main mode of cell death in both cell models, as assessed by annexin V-FITC and acridine orange/ethidium bromide staining. MRK-107 is a selective, redox-active compound with pro-oxidant and pro-apoptotic properties and the capacity to activate antiproliferative pathways, showing promise in anticancer drug research.

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

“…Imidazo[1,2- a ]pyridine is a privileged structure that plays an important role in organic synthesis and in the pharmaceutical industry. This scaffold is present in drugs with several biological activities, such as antiviral [ 1 ], anticonvulsant [ 2 ], antibacterial [ 3 ], antipyretic [ 4 ], antituberculosis [ 5 ], anticancer [ 6 ], anthelmintic [ 5 ], antifungal [ 7 ], analgesic [ 8 ], antiulcer [ 9 ], antiprotozoal [ 10 ], antitumor [ 11 ], and anti-inflammatory [ 12 ]. Examples of commercial drugs are depicted in Figure 1 [ 13 ] and include alpidem (anxiety disorders), minodronic acid (osteoporosis), miroprofen (non-steroidal anti-inflammatory drug, NSAID), necopidem (insomnia), olprinone (acute heart failure), saripidem (type A GABA receptor agonist), zolimidine (gastroesophageal reflux disease), and zolpidem (insomnia).…”

Investigation of the Potential Targets behind the Promising and Highly Selective Antileishmanial Action of Synthetic Flavonoid Derivatives

“…As part of our research interest in synthesis and biological evaluation of heterocyclic compounds, − herein, we aimed to deeply analyze the antileishmanial action of the set of synthetic flavonol and chalcone derivatives. Considering the alarming situation involving CL, the species L. amazonensis was chosen to carry out the experimental tests.…”