Study of the biotransformation of a new sydnonimine derivative with predominant cerebral vasodilatory activity

Авторы

  • Никита С. Попов Тверской государственный медицинский университет ORCID logo https://orcid.org/0000-0002-1792-7414
  • Дмитрий А. Гавриленко Тверской государственный медицинский университет ORCID logo https://orcid.org/0009-0003-8692-0878
  • Роман Д. Павлов Тверской государственный медицинский университет ORCID logo https://orcid.org/0009-0006-1215-6979
  • Михаил С. Баранов Институт биоорганической химии им. Шемякина-Овчинникова Российской академии наук ORCID logo https://orcid.org/0000-0002-9339-7603
  • Диана Е. Каурова Российский национальный научно-исследовательский медицинский университет им. Н.И. Пирогова ORCID logo https://orcid.org/0000-0002-6261-9832
  • Иван Н. Мяснянко Российский национальный научно-исследовательский медицинский университет им. Н.И. Пирогова ORCID logo https://orcid.org/0000-0002-2168-3555
  • Дмитрий С. Иванов Институт биоорганической химии им. Шемякина-Овчинникова Российской академии наук
  • Вадим Ю. Балабанян Российский национальный научно-исследовательский медицинский университет им. Н.И. Пирогова ORCID logo https://orcid.org/0000-0002-5744-7060

DOI:

https://doi.org/10.18413/rrpharmacology.11.1042

Аннотация

Introduction: Sydnonimines are a promising group of drugs for development of novel substances with predominant cerebral vasodilatory activity. One of them is experimental compound with laboratory code BBP20233. The mechanism of action of BBP2023 compound is tied to its metabolites. This study aims for identification of biotransformation products of BBP2023 using HPLC-MS/MS method.

Materials and Methods: Identification of BBP2023 biotransformation products was performed in male rats and male rabbits after intragastric administration of BBP2023 in form of oil emulsion. Blood samples were collected before and 1 and 8 hours after administration. Urine samples from rats were collected before and 24 hours after administration. Additionally, complete liver isolation was performed in another group of rats to investigate liver’s role in BBP2023 metabolism. Identification of products was performed using HPLC-MS/MS method as well as UHR-TOF method.

Results and Discussion: Analysis of rat plasma samples collected 1 hour after administration revealed the presence of parent compound, active metabolite SIN, geranamine and various isomers of OH-derivatives. Analysis of rat urine samples collected 24 hours after administration showed the presence of glucuronic acid conjugates of SIN and parent compound. Similar results were obtained from rabbit plasma samples, although with less variety of hydroxylated derivative isomers.

Conclusion: Investigated features of BBP2023 biotransformation require detailed analysis of pharmacokinetics for both BBP2023 and its metabolites to determine their role in therapeutic effect and possible adverse effects.

Графическая аннотация

Ключевые слова:

biotransformation, pharmacokinetics, sydnonimines, vasodilators, chromatography-mass spectrometry

Библиографические ссылки

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Вклад авторов

Никита С. Попов, Тверской государственный медицинский университет

PhD in Pharmaceutical Sciences, Associate Professor, Head of the Center for Pharmaceutical and Bioanalytical Research, Associate Professor of the Department of Pharmacology, Tver State Medical University, Tver, Russia; e-mail: popov@mail.ru; ORCID ID: https://orcid.org/0000-0002-1792-7414. The author contributed to the mass spectrometric metabolite identification, bioanalytical method development, and manuscript preparation.

Дмитрий А. Гавриленко, Тверской государственный медицинский университет

Teaching assistant, Department of Chemistry, Assistant at the Department of Pharmacology, Tver, State Medical University, Tver, Russia; e-mail: dimirdome@gmail.com; ORCID ID: https://orcid.org/0009-0003-8692-0878. The author contributed to the literature review, biological study execution, results analysis, and manuscript preparation.

Роман Д. Павлов, Тверской государственный медицинский университет

5th year student, the Faculty of General Medicine, Tver State Medical University, Tver, Russia; e-mail: pavlov.2002@mail.ru; ORCID ID: https://orcid.org/0009-0006-1215-6979. The author contributed to the surgical procedures on laboratory animals, and manuscript preparation.

Михаил С. Баранов, Институт биоорганической химии им. Шемякина-Овчинникова Российской академии наук

Doctor Habilit. of Chemical Sciences, Lead researcher at the Laboratory of Heterocyclic Compounds Chemistry, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia; e-mail: baranovmikes@gmail.com; ORCID ID: https://orcid.org/0000-0002-9339-7603. The author contributed to the research concept development, metabolite synthesis, and manuscript preparation.

Диана Е. Каурова, Российский национальный научно-исследовательский медицинский университет им. Н.И. Пирогова

PhD in Pharmaceutical Sciences, Senior Researcher at the Research Laboratory of Medicinal Substances Chemistry, Research Institute of Translational Medicine, N.I. Pirogov Russian National Research Medical University, Moscow, Russia; e-mail: berseneva_diana@mail.ru; ORCID ID: https://orcid.org/0000-0002-6261-9832. The author contributed to the literature review, results analysis, and manuscript preparation.

Иван Н. Мяснянко, Российский национальный научно-исследовательский медицинский университет им. Н.И. Пирогова

PhD in Chemical Sciences, Junior Researcher, Head of the Research Laboratory of Medicinal Substances Chemistry, Research Institute of Translational Medicine, N.I. Pirogov Russian National Research Medical University, Moscow, Russia; e-mail: conzbutcher@gmail.com; ORCID ID: https://orcid.org/0000-0002-2168-3555. The author contributed to the research concept development, metabolite synthesis, and manuscript preparation.

Дмитрий С. Иванов, Институт биоорганической химии им. Шемякина-Овчинникова Российской академии наук

Laboratory Technician at the Laboratory of Heterocyclic Compounds Chemistry, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia; e-mail: d-ivanov.dmitry@yandex.ru. The author contributed to the research concept development, metabolite synthesis, and manuscript preparation.

Вадим Ю. Балабанян, Российский национальный научно-исследовательский медицинский университет им. Н.И. Пирогова

Doctor Habil. of Pharmaceutical Sciences, Associate Professor, Leading Researcher at the Research Laboratory of Medicinal Substances Chemistry, Research Institute of Translational Medicine, N.I. Pirogov Russian National Research Medical University, Moscow, Russia; e-mail: pharm@mail.ru; ORCID ID: https://orcid.org/0000-0002-5744-7060. The author contributed to the study objective formulation, research design development, and manuscript preparation.

Загрузки

Опубликован

29.12.2025

Как цитировать

Popov NS, Gavrilenko DA, Pavlov RD, Baranov MS, Kaurova DE, Myasnyanko IN, Ivanov DS, Balabanyan VY (2025) Study of the biotransformation of a new sydnonimine derivative with predominant cerebral vasodilatory activity. Research Results in Pharmacology 11(4): 258–271. https://doi.org/10.18413/rrpharmacology.11.1042

Выпуск

Том 11 № 4 (2025)

Раздел

Экспериментальная фармакология

Лицензия

Copyright (c) 2025 Popov NS, Gavrilenko DA, Pavlov RD, Baranov MS, Kaurova DE, Myasnyanko IN, Ivanov DS, Balabanyan VYu

Лицензия Creative Commons

Это произведение доступно по лицензии Creative Commons «Attribution» («Атрибуция») 4.0 Всемирная.