Drugs and Drug Candidates

Background/Objectives: Vincamine is an indole alkaloid initially isolated from plants of the Vinca genus and has previously been demonstrated to have antioxidant, hypoglycemic, and hypolipidemic activities. Vinpocetine, a synthetic derivative of vincamine with an enhanced pharmacological profile, has demonstrated promising antiproliferative properties. While previously reported vinpocetine derivatives have undergone extensive investigation for their pharmacological properties, the role of the E-ring ethyl ester in the antiproliferative properties of compounds with this scaffold has not yet been fully described. Methods: Here, the antiproliferative activity of two vinpocetine analogs with modifications at the E-ring was evaluated through cell viability and LDH assays, and their mechanism of action was investigated through cell cycle analysis, apoptosis detection, and reporter assays for Wnt-1, NF-κB, and STAT3 signaling. Results: Cell viability assays revealed that reduction of the ethyl ester to an alcohol exhibited strong dose-dependent antiproliferative activity across five mammalian cell lines, but did not induce significant markers of apoptosis or necrotic death as determined by FITC/Annexin V and cell cycle flow cytometry, respectively. Through label-free cell imaging, we found the antiproliferative activity of vinpocetine alcohol to be correlated with a decrease in membrane integrity in treated cells. We further observe that both analogs exhibit dose-dependent modulation of TCF/LEF, NF-kB, and STAT3 reporter cells, which appears to be coupled with trends in antiproliferative activity. Conclusions: Altogether, this work demonstrates the potential for E-ring modifications of vinpocetine as antiproliferative agents.

Introduction: The increasing prevalence of fungal infections, particularly those caused by Candida albicans, presents a significant clinical challenge due to the emergence of drug-resistant strains. Silver (I) coordination complexes show promise as antifungal agents; however, their poor water solubility limits clinical application. Methods: In this study, we developed and characterized a lipid nanoemulsion (Ag-LN) to enhance the delivery and activity of a silver (I) complex. Results: The formulation exhibited nanoscale size, spherical morphology, and stability for up to 60 days. Ag-LN showed potent antifungal effects, preventing biofilm formation and eradicating mature biofilms. Importantly, nanoencapsulation preserved antifungal activity while reducing mutagenic potential and acute toxicity compared with the free compound. Conclusions: These findings support Ag-LN as a promising antifungal platform for future preclinical studies.

Background: Type 2 diabetes mellitus (T2DM) is a complex metabolic disease requiring multi-targeted therapeutic strategies. Gunnera perpensa and Erythrina zeyheri are traditionally used in diabetes management, but their mechanisms remain poorly understood. Methods: This study used in vitro, metabolomics, and network pharmacology approaches to elucidate their antidiabetic potential. Leaf extracts were screened for glucose utilization in C2C12 cells, and cytotoxicity in Vero cells. Metabolites profiled via GC×GC-TOF-MS and those retrieved from Phytochemical Interaction Database were evaluated for drug-likeness and target prediction using SwissADME and SwissTargetPrediction. Diabetes-related targets were obtained from databases, and overlapping targets were used to construct interaction networks using Cytoscape and STRING. Functional enrichment analyses were conducted via DAVID for GO and KEGG pathways. Results: G. perpensa acetone and methanol extracts enhanced superior glucose utilization (IC₅₀ = 78.5 and 94.8 µg/mL, respectively), with low cytotoxicity (LC₅₀ > 600 µg/mL). Key compounds including arabinose, identified from both plants, showed multi-target binding potential against STAT3, PIK3RI and JAK2. Enrichment analyses revealed pathways related to insulin signaling, inflammation, and glucose metabolism. Conclusions: This study supports the therapeutic relevance of phytochemical synergy in the traditional use of both plants and demonstrated systems-level approaches for elucidating complex drug–target interactions in T2DM.