Drugs and Drug Candidates

Background/Objectives: Bauhinia cheilantha Bong. Steud. (Leguminosae; “pata-de-vaca”) is traditionally used in folk medicine for its antidiabetic, anti-inflammatory, and sedative properties. This study aimed to evaluate aqueous leaf extracts of B. cheilantha, non-delipidated and delipidated, regarding their phytochemical composition, phenolic profile, antioxidant potential, and cytotoxic, genotoxic, and antigenotoxic effects. Methods: Phytochemical screening was performed by TLC, and phenolic compounds were determined by HPLC. Antioxidant activity was assessed using DPPH, ABTS, and phosphomolybdenum assays. Cytotoxicity, genotoxicity, and antigenotoxicity were evaluated in L929 murine fibroblast cells using MTT and cytokinesis-block micronucleus (CBMN) assays. Results: Both extracts contained anthocyanins, phenolics, lignans, saponins, and hydrolyzable tannins. The delipidated extract showed higher total phenolic content (17.54 mg/kg) than the non-delipidated (13.76 mg/kg). Major constituents included kaempferol 3-glucoside, quercetin, hesperidin, naringenin, and t-cinnamic acid. Antioxidant assays revealed EC₅₀ values of 25.84, 13.60, and 66.09 µg/mL for the non-delipidated extract, and 26.19, 16.34, and 52.78 µg/mL for the delipidated extract in the DPPH, ABTS, and phosphomolybdenum assays, respectively. No cytotoxicity was observed, except at 1600 µg/mL for the non-delipidated extract and 800–1600 µg/mL for the delipidated extract. Genotoxicity occurred only at 400 µg/mL. Antigenotoxic evaluation showed that the non-delipidated extract (100 µg/mL) reduced methyl methanesulfonate-induced chromosomal damage in simultaneous and post-treatment conditions, while the delipidated extract was only effective for post-treatment. Conclusions: Aqueous extracts of B. cheilantha exhibit antioxidant and antigenotoxic properties. At active concentrations, they were non-cytotoxic and non-genotoxic. The non-delipidated extract, in particular, showed the strongest genome-protective potential, supporting its traditional use and highlighting its relevance in the development of natural therapeutic agents.

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.