Current Topics in Medicinal Chemistry - Volume 24, Issue 14, 2024

Liposomes, spherical particles with phospholipid double layers, have been extensively studied over the years as a means of drug administration. Conventional manufacturing techniques like thin-film hydration and extrusion have limitations in controlling liposome size and distribution. Microfluidics enables superior tuning of parameters during the self-assembly of liposomes, producing uniform populations. This review summarizes microfluidic methods for engineering liposomes, including hydrodynamic flow focusing, jetting, micro mixing, and double emulsions. The precise control over size and lamellarity afforded by microfluidics has advantages for cancer therapy. Liposomes created through microfluidics and designed to encapsulate chemotherapy drugs have exhibited several advantageous properties in cancer treatment. They showcase enhanced permeability and retention effects, allowing them to accumulate specifically in tumor tissues passively. This passive targeting of tumors results in improved drug delivery and efficacy while reducing systemic toxicity. Promising results have been observed in pancreatic, lung, breast, and ovarian cancer models, making them a potential breakthrough in cancer therapy. Surface-modified liposomes, like antibodies or carbohydrates, also achieve active targeting. Overall, microfluidic fabrication improves reproducibility and scalability compared to traditional methods while maintaining drug loading and biological efficacy. Microfluidics-engineered liposomal formulations hold significant potential to overcome challenges in nanomedicine-based cancer treatment.

Many food-derived peptides have the potential to improve brain health and slow down neurodegeneration. Peptides are produced by the enzymatic hydrolysis of proteins from different food sources. These peptides have been shown to be involved in antioxidant and anti-inflammatory activity, neuro-transmission modulation, and gene expression regulation. Although few peptides directly affect chromatin remodeling and histone alterations, others indirectly affect the neuroprotection process by interfering with epigenetic changes. Fish-derived peptides have shown neuroprotective properties that reduce oxidative stress and improve motor dysfunction in Parkinson's disease models. Peptides from milk and eggs have been found to have anti-inflammatory properties that reduce inflammation and improve cognitive function in Alzheimer's disease models. These peptides are potential therapeutics for neurodegenerative diseases, but more study is required to assess their efficacy and the underlying neuroprotective benefits. Consequently, this review concentrated on each mechanism of action used by food-derived peptides that have neuroprotective advantages and applications in treating neurodegenerative diseases. This article highlights various pathways, such as inflammatory pathways, major oxidant pathways, apoptotic pathways, neurotransmitter modulation, and gene regulation through which food-derived peptides interact at the cellular level.

Several classes of compounds are applied in clinics due to their immunosuppressive properties in transplantology and the treatment of autoimmune diseases. Derivatives of mycophenolic acid, corticosteroids and chemotherapeutics bearing heterocyclic moieties like methotrexate, azathioprine, mizoribine, and ruxolitinib are active substances with investigated mechanisms of action. However, improved synthetic approaches of known drugs and novel derivatives are still being reported to attempt better accessibility and therapeutic properties. In this review article, we present the synthesis of the designed chemical structures based on recent literature reports concerning novel compounds as promising immunosuppressive drugs. Moreover, some of the discussed derivers revealed also other types of activities with prospective medicinal potential.

Background: Inflammation is a series of complex defense-related reactions. The inflammation cascade produces various pro-inflammatory mediators. Unregulated production of these pro-inflammatory mediators can lead to a wide range of diseases, including rheumatoid arthritis, sepsis, and inflammatory bowel disease. In the literature, the anti-inflammatory action of quinoline and thiazolidinedione nuclei are well established, alone, and associated with other nuclei. The synthesis of hybrid molecules is a strategy for obtaining more efficient molecules due to the union of pharmacophoric nuclei known to be related to pharmacological activity. Objectives: Based on this, this work presents the synthesis of thiazolidinedione-quinoline molecular hybrids and their involvement in the modulation of cytokines involved in the inflammatory reaction cascade. Methods: After synthesis and characterization, the compounds were submitted to cell viability test (MTT), ELISA IFN-γ and TNF-α, adipogenic differentiation, and molecular docking assay with PPARy and COX-2 targets. Results: LPSF/ZKD2 and LPSF/ZKD7 showed a significant decrease in the concentration of IFN- γ and TNF-α, with a dose-dependent behavior. LPSF/ZKD4 at a concentration of 50 μM significantly reduced IL-6 expression. LPSF/ZKD4 demonstrates lipid accumulation with significant differences between the untreated and negative control groups, indicating a relevant agonist action on the PPARγ receptor. Molecular docking showed that all synthesized compounds have good affinity with PPARγ e COX-2, with binding energy close to -10,000 Kcal/mol. Conclusion: These results demonstrate that the synthesis of quinoline-thiazolidinedione hybrids may be a useful strategy for obtaining promising candidates for new anti-inflammatory agents.