Browsing by Author "Molina, Alfredo"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Publication Antimigratory Effect of Lipophilic Cations Derived from Gallic and Gentisic Acid and Synergistic Effect with 5-Fluorouracil on Metastatic Colorectal Cancer Cells: A New Synthesis Route(2024) Suárez, Cristian; Jara, José; Cortés, Gonzalo; Rojas, Diego; Araya, Gabriel; Molina, Alfredo; González, Fabiola; Fuentes, Sebastián; Aránguiz, Pablo; Campodónico, Paola; Maya, Juan; Vivar, Raúl; Catalán, MabelColorectal cancer (CRC) is the third leading cause of cancer deaths in the world. Standard drugs currently used for the treatment of advanced CRC-such as 5-fluorouracil (5FU)-remain unsatisfactory in their results due to their high toxicity, high resistance, and adverse effects. In recent years, mitochondria have become an attractive target for cancer therapy due to higher transmembrane mitochondrial potential. We synthesized gallic acid derivatives linked to a ten-carbon aliphatic chain associated with triphenylphosphonium (TPP+C10), a lipophilic cationic molecule that induces the uncoupling of the electron transport chain (ETC). Other derivatives, such as gentisic acid (GA-TPP+C10), have the same effects on colorectal cancer cells. Although part of our group had previously reported preparing these structures by a convergent synthesis route, including their application via flow chemistry, there was no precedent for a new methodology for preparing these compounds. In this scenario, this study aims to develop a new linear synthesis strategy involving an essential step of Steglich esterification under mild conditions (open flask) and a high degree of reproducibility. Moreover, the study seeks to associate GA-TPP+C10 with 5FU to evaluate synergistic antineoplastic effects. In addition, we assess the antimigratory effect of GA-TPP+C10 and TPP+C10 using human and mouse metastatic CRC cell lines. The results show a new and efficient synthesis route of these compounds, having synergistic effects in combination with 5FU, increasing apoptosis and enhancing cytotoxic properties. Additionally, the results show a robust antimigratory effect of GATPP+C10 and TPP+C10, reducing the activation pathways linked to tumor progression and reducing the expression of VEGF and MMP-2 and MMP-9, common biomarkers of advanced CRC. Moreover, TPP+C10 and GA-TPP+C10 increase the activity of metabolic signaling pathways through AMPK activation. The data allow us to conclude that these compounds can be used for in vivo evaluations and are a promising alternative associated with conventional therapies for advanced colorectal cancer. Additionally, the reported intermediates of the new synthesis route could give rise to analog compounds with improved therapeutic activity.Publication Therapeutic challenges in central nervous system viral infections: advancing mesenchymal stem cell-based strategies for treating neuroinflammation and promoting tissue repair(2025) Carbone, Javier; Fontecilla, Javiera; Sales, Nicolás; Chaparro, William; Molina, Alfredo; Ruete, María; González, Pablo; Machuca, Mayra; Opazo, Ma Cecilia; Ezquer, Marcelo; Duarte, LuisaAlthough significant progress has been made in medicine and antimicrobial research, viral infections continue to pose a critical global health challenge, particularly when they involve the central nervous system (CNS). Despite advances in vaccines, antiviral agents, and small molecule therapeutics, current strategies remain insufficient to address the complex consequences of many CNS infections fully. Notably, many viruses are neurotropic and can invade the CNS, triggering infectious neuroinflammation that often lead to chronic neurological disorders and lasting morbidity. Current therapeutic approaches are largely ineffective in preventing or reversing this long-term neurological damage, underscoring the urgent need for innovative prophylactic and therapeutic interventions. Mesenchymal stem cells (MSCs) have emerged as a promising strategy to counteract chronic neuroinflammation and promote tissue repair following viral CNS infections. This review provides a comprehensive overview of CNS viral infection and neuroinflammation, including epidemiology and pathophysiology, and critically examines the limitations of existing treatments, particularly their inability to mitigate persistent neurological sequelae. Furthermore, we summarize recent preclinical and clinical studies investigating the use of MSCs in the context of CNS viral infections, highlighting their immunomodulatory and neuroprotective mechanisms, and discuss the challenges and future directions for MSC-based therapies in clinical settings.