Mirela Nicolov

Background: This study evaluates the translational relevance of free computer-assisted ADMET platforms in drug discovery by comparing SwissADME and FAF-Drugs4 predictions with regulatory and curated reference data for approved anticancer drugs. Methods: Fourteen approved anticancer agents representing diverse chemical classes were analyzed using SwissADME and FAF-Drugs4. We compared predicted physicochemical, pharmacokinetic, and toxicity-related properties with information extracted from FDA- and EMA-approved product information, DrugBank, and PubChem. We evaluated the concordance for oral absorption, permeability, metabolic stability, and toxicity-related trends. Results: The platforms showed good concordance for broad descriptor-driven properties, particularly oral suitability and physicochemical trends. Strong agreement was observed for intravenously administered taxanes, which displayed unfavorable oral drug characteristics, and for several orally active small molecules with generally compatible profiles. Partial concordance was observed for compounds such as temozolomide, whose clinical behavior is influenced by factors not fully captured by descriptor-based models. Toxicity outputs were informative as early warning signals, with vandetanib showing the clearest alignment between predicted elevated risk and documented safety concerns. Conclusions: Free computational ADMET tools are valuable computer-assisted drug discovery resources for early triage, predictive toxicology, and prioritization of repositioning candidates, but they should complement rigorous experimental and clinical evaluation.

The high incidence of melanoma leading to a poor prognosis rate endorses the development of alternative and innovative approaches in the treatment of melanoma. Therefore, the present study aims to develop and characterize, in terms of physicochemical features and biological impact, an aqueous suspension of magnetite (Fe₃O₄) coated with β-cyclodextrin (Fe₃O₄@β-CD) as a potential innovative alternative nanosystem for melanoma therapy. The nanosystem exhibited physicochemical characteristics suitable for biological applications, revealing a successful complexation of Fe₃O₄ NPs with β-CD and an average size of 18.1 ± 2.1 nm. In addition, the in vitro evaluations revealed that the newly developed nanosystem presented high biocompatibility on a human keratinocyte (HaCaT) monolayer and selective antiproliferative activity on amelanotic human melanoma (A375) cells, inducing early apoptosis features when concentrations of 10, 15, and 20 μg/mL were employed for 48 h and 72 h. Collectively, the Fe₃O₄@β-CD nanosystem reveals promising features for an adjuvant approach in melanoma treatment, mainly due to its β-cyclodextrin coating, thus endorsing a potential co-loading of therapeutic drugs. Furthermore, the intrinsic magnetic core of Fe₃O₄ NPs supports the magnetically based cancer treatment strategies.