Structural-fragment analysis of active pharmaceutical ingredients of antiepileptic drugs in group N03A of the Ukrainian pharmaceutical market and their pharmacophoric features

Authors

DOI:

https://doi.org/10.15587/2519-4852.2025.337842

Keywords:

antiepileptic drugs, APIs, FBDD, pharmacophore, structural clustering, ADME, Tanimoto similarity, NaV, GABA-A, SV2A, carbonic anhydrase, Ukrainian pharmaceutical market

Abstract

Epilepsy affects approximately 50 million people globally, with one-third of patients remaining resistant to available therapies, emphasizing the need for new and safer anticonvulsants. Although fragment-based and in silico approaches are effective for drug discovery, a unified structural analysis of antiepileptic APIs on the Ukrainian market remains unexplored.

The aim of the study. To analyze 16 antiepileptic APIs registered in Ukraine using fragment-based methods to identify shared pharmacophoric features, structural similarities, and correlations between structural fragments and ADME properties (including drug-likeness patterns for structure-property insights) as a basis for rational anticonvulsant design.

Materials and methods. Data were collected from the State Register of Medicinal Products of Ukraine and Compendium (June 2025) using ATC code N03A. Literature review used PubMed, PubChem, DrugBank, Scopus, Elicit, and ResearchRabbit. Structural analysis was performed using Python libraries.

Results. The study classified 16 active pharmaceutical ingredients (APIs) into structural clusters (e.g., barbiturates, dibenzazepines, amino acid derivatives) based on Tanimoto similarity coefficients and ECFP4 molecular fingerprints. Commonly identified fragments included carbonyl, amino, amide, carboxyl groups, and aromatic rings. ADME profiling revealed consistent relationships between structural features and physicochemical properties: high lipophilicity in benzodiazepines and good absorption characteristics in gabapentinoids. This analysis was performed to identify structure-dependent ADME patterns, providing a basis for fragment-based design of novel anticonvulsants.

Conclusions. Despite chemical diversity, the analyzed APIs exhibit shared spatial pharmacophore arrangements with recurring groups supporting activity at NaV, CaV, GABA-A, SV2A, and GABA-T. ADME profiling and structure–property correlations provide a basis for pharmacophore fragment modelling and CNS-oriented fragment-library design to enable rational discovery. Future design should leverage the identified pharmacophoric fragments to build multitarget molecules within a CNS ADME window

Supporting Agency

  • The study was carried out within the framework of the research project “ Search for novel potential anticonvulsant agents for the treatment of post-traumatic epilepsy in military personnel and the civilian population”, funded by the Ministry of Education and Science of Ukraine (Project registration number: 0125U001794).

Author Biographies

Maryna Stasevych, Lviv Polytechnic National University

Doctor of Chemical Sciences, Professor

Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology

Mykhailo Hoidyk, Danylo Halytsky Lviv National Medical University

PhD Student

Department of Pharmaceutical, Organic and Bioorganic Chemistry

Olexandra Roman, Danylo Halytsky Lviv National Medical University

PhD, Associate Professor

Department of General, Bioinorganic, Physicocolloid Chemistry

Roksolana Konechna, Lviv Polytechnic National University

PhD, Associate Professor

Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology

Andriy Karkhut, Lviv Polytechnic National University

PhD, Associate Professor

Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology

Andrii Lozynskyi, Danylo Halytsky Lviv National Medical University

Doctor of Pharmaceutical Sciences, Professor

Department of Pharmaceutical, Organic and Bioorganic Chemistry

Sviatoslav Polovkovych, Lviv Polytechnic National University

Doctor of Chemical Sciences, Professor

Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology

Roman Lesyk, Danylo Halytsky Lviv National Medical University

Doctor of Pharmaceutical Sciences, Professor

Department of Pharmaceutical, Organic and Bioorganic Chemistry

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Structural-fragment analysis of active pharmaceutical ingredients of antiepileptic drugs in group N03A of the Ukrainian pharmaceutical market and their pharmacophoric features

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2025-08-30

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Stasevych, M., Hoidyk, M., Roman, O., Konechna, R., Karkhut, A., Lozynskyi, A., Polovkovych, S., & Lesyk, R. (2025). Structural-fragment analysis of active pharmaceutical ingredients of antiepileptic drugs in group N03A of the Ukrainian pharmaceutical market and their pharmacophoric features. ScienceRise: Pharmaceutical Science, (4 (56), 20–34. https://doi.org/10.15587/2519-4852.2025.337842

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No. 4 (56) (2025)

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Pharmaceutical Science

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Copyright (c) 2025 Maryna Stasevych, Mykhailo Hoidyk, Olexandra Roman, Roksolana Konechna, Andriy Karkhut, Andrii Lozynskyi, Sviatoslav Polovkovych, Roman Lesyk

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