2025 / 03

DOI: 10.24075/brsmu.2025.026
Copyright: © 2025 by the authors. Licensee: Pirogov University.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (CC BY).

ORIGINAL RESEARCH

In vivo assessment of the role of liver metabolism in sydnone imine biotransformation

Popov NS1, Terekhov VM1, Baranov MS2, Balabanyan VYu2, Kaurova DE2, Myasnyanko IN2, Terekhova EA1
About authors

1 Tver State Medical University, Tver, Russia

2 Research Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russia

Correspondence should be addressed: Nikita S. Popov
Sovetskaya, 4, Tver, 170100, Russia; ur.liam@vopop.sn

About paper

Funding: the study was carried out under the state assignment for the research project “Development of the Candidate Drug Possessing Mostly Central Vasodilatory Activity for Treatment of Cerebrovascular Disorders”, state registration number 124020900020-4.

Author contribution: Popov NS — search for the BBP2023 compound metabolites, bioanalytical method development, manuscript writing; Terekhov VM — developing the design of vascular liver isolation in rats, surgical procedure; Baranov MS — synthesis of the BBP2023 compound and its metabolites, manuscript writing; Balabanyan VYu — goal setting, developing the study design, manuscript writing, Kaurova DE — literature review, manuscript writing; Myasnyanko IN — synthesis of the BBP2023 compound and its metabolites, manuscript writing; Terekhova EA — developing the design of vascular liver isolation in rats, surgical procedure; all authors contributed to the publication equally, they confirm compliance of authorship with the ICMJE international criteria.

Compliance with ethical standards: the study was approved by the Ethics Committee of the Tver State Medical University (protocol No. 5 dated 19 June 2024). All experiments were conducted in accordance with the principles of Good Laboratory Practice (Order of the Ministry of Health of the Russian Federation No. 708n of 23.08.2010, Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes).

Received: 2025-04-16 Accepted: 2025-04-30 Published online: 2025-05-15
|
  1. Shanu-Wilson J, Evans L, Wrigley S, Steele J, Atherton J, Boer J. Biotransformation: impact and application of metabolism in drug discovery. ACS Medicinal Chemistry Letter. 2020; 11 (11): 2087– 2107. DOI: 10.1021/acsmedchemlett.0c00202.
  2. Baillie TA, Rettie AE. Role of biotransformation in drug-induced toxicity: influence of intra-and inter-species differences in drug metabolism. Drug metabolism and pharmacokinetics. 2011; 26 (1): 15–29. DOI: 10.2133/dmpk.DMPK-10-RV-089.
  3. Obach RS. Pharmacologically active drug metabolites: impact on drug discovery and pharmacotherapy. Pharmacological reviews. 2013; 65 (2): 578–640. DOI: 10.1124/pr.111.005439.
  4. Fura A. Role of pharmacologically active metabolites in drug discovery and development. Drug discovery today. 2006; 11 (3–4): 133–42. DOI: 10.1016/S1359-6446(05)03681-0.
  5. Mahanur V, Rajge R, Tawar MA. Review on emerging oral dosage forms which helps to bypass the hepatic first pass metabolism. Asian Journal of Pharmacy and Technology. 2022; 12 (1): 47–52. DOI: 10.52711/2231-5713.2022.00009.
  6. Klomp F, Wenzel C, Drozdzik M, Oswald S. Drug–drug interactions involving intestinal and hepatic CYP1A enzymes. Pharmaceutics. 2020; 12 (12): 1201. DOI: 10.3390/pharmaceutics12121201.
  7. Cerny MA, Kalgutkar AS, Obach RS, Sharma R, Spracklin DK, Walker GS. Effective application of metabolite profiling in drug design and discovery. Journal of Medicinal Chemistry. 2020; 63 (12): 6387–406. DOI: 10.1021/acs.jmedchem.9b01840.
  8. Rai M, Paudel N, Sakhrie M, Gemmati D, Khan IA, Tisato V, Singh AV. Perspective on quantitative structure–toxicity relationship (QSTR) models to predict hepatic biotransformation of xenobiotics. Livers. 2023; 3 (3): 448–62. DOI: 10.3390/livers3030032.
  9. Peeters L, Vervliet P, Foubert K, Hermans N, Pieters L, Covaci A. A comparative study on the in vitro biotransformation of medicagenic acid using human liver microsomes and S9 fractions. Chemico-Biological Interactions. 2020; 328: 109192. DOI: 10.1016/j.cbi.2020.109192.
  10. Horspool AM, Wang T, Scaringella YS, Taub ME, Chan TS. Human liver microsomes immobilized on magnetizable beads: a novel approach to study in vitro drug metabolism. Drug Metabolism and Disposition. 2020; 48 (8): 645–654. DOI: 10.1124/dmd.120.090696.
  11. Ooka M, Lynch C, Xia M. Application of in vitro metabolism activation in high-throughput screening. International journal of molecular sciences. 2020; 21 (21): 8182. DOI: 10.3390/ijms21218182.
  12. Knights KM, Stresser DM, Miners JO, Crespi CL. In vitro drug metabolism using liver microsomes. Current protocols in pharmacology. 2016; 74 (1): 7–8. DOI: 10.1002/cpph.9.
  13. Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Human drug metabolism and the cytochromes P450: application and relevance of in vitro models. The Journal of Clinical Pharmacology. 2001; 41 (11): 1149–79. DOI: 10.1177/00912700122012724.
  14. Pelkonen O, Raunio H. In vitro screening of drug metabolism during drug development: can we trust the predictions? Expert opinion on drug metabolism & toxicology. 2005; 1 (1): 49–59. DOI: 10.1517/17425255.1.1.49.
  15. Zhu C, Wan M, Cheng H, Wang H, Zhu M, Wu C. Rapid detection and structural characterization of verapamil metabolites in rats by UPLC–MSE and UNIFI platform. Biomedical Chromatography. 2020; 34 (1): e4702. DOI: 10.1002/bmc.4702.
  16. Lee K, Lee JY, Lee K, Jung CR, Kim MJ, Kim JA, Oh SJ. Metabolite profiling and characterization of LW6, a novel HIF-1α inhibitor, as an antitumor drug candidate in mice. Molecules. 2021; 26 (7): 1951. DOI: 10.3390/molecules26071951.