Synthesis of triazole-containing ciprofloxacin conjugate and its in silico test as a cytochrome P450 ligand

  • Yaroslav V. Faletrov Research Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus; Belarusian State University, 4 Niezaliežnasci Avenue, Minsk 220030, Belarus https://orcid.org/0000-0001-8168-5897
  • Liliya I. Glinskaya Belarusian State University, 4 Niezaliežnasci Avenue, Minsk 220030, Belarus
  • Matvey S. Horetski Research Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus; Belarusian State University, 4 Niezaliežnasci Avenue, Minsk 220030, Belarus
  • Jan V. Panada Research Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus
  • Nina S. Frolova Research Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus
  • Vladimir M. Shkumatov Research Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus; Belarusian State University, 4 Niezaliežnasci Avenue, Minsk 220030, Belarus
DOI: https://doi.org/10.33581/2520-257X-2021-1-21-27

Abstract

Cytochromes P450 are hem-containing monooxygenases which catalyse biosynthesis of many compounds playing an essential role in cellular functions as well as degradation of drugs and xenobiotics. Some P450s (e. g., human CYP19 and CYP17, fungal CYP51) are valid target proteins for some drugs. The others P450s are also interesting for pharmacology-related researches. Aiming to design new fluorescent inhibitor of P450s we have synthesised the azole-bearing conjugate of ciprofloxacin (CPF-bab-Z1). To estimate potential of the compound as a ligand for CYPs we performed high-throughput virtual screening (multiple docking calculations) for CPF-bab-Z1 and multiple known 3D structures of P450s. The best affinity for CPF-bab-Z1 (the smallest value of energy of binding is equal -12.5 kcal/mol) were found for protein with PDB code 5esh among 28 structures of CYP51. The calculated pose of CPF-bab-Z1 in the active site of the protein is characterised by cyclopropyl (but not azole) proximity to the heme iron of the CYP51. The data obtained demonstrate perspectives for in vitro investigations of CPF-bab-Z1 with P450s.

Author Biographies

Yaroslav V. Faletrov, Research Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus; Belarusian State University, 4 Niezaliežnasci Avenue, Minsk 220030, Belarus

PhD (chemistry), docent; leading researcher at the laboratory of biochemistry of drugs, Research Institute for Physical Chemical Problems, Belarusian State University; associate professor at the department of macromolecular compounds, faculty of chemistry, Belarusian State University 

Liliya I. Glinskaya, Belarusian State University, 4 Niezaliežnasci Avenue, Minsk 220030, Belarus

student at the faculty of chemistry

Matvey S. Horetski, Research Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus; Belarusian State University, 4 Niezaliežnasci Avenue, Minsk 220030, Belarus

junior researcher at the laboratory of biochemistry of drugs, Research Institute for Physical Chemical Problems, Belarusian State University; assistant at the department of macromolecular compounds, faculty of chemistry, Belarusian State University.

Jan V. Panada, Research Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus

junior researcher at the laboratory of biochemistry of drugs

Nina S. Frolova, Research Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus

researcher at the laboratory of biochemistry of drugs

Vladimir M. Shkumatov, Research Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus; Belarusian State University, 4 Niezaliežnasci Avenue, Minsk 220030, Belarus

corresponding member of the National Academy of Sciences of Belarus, doctor of science (biology), full professor; chief researcher at the laboratory of biochemistry of drugs, Research Institute for Physical Chemical Problems, Belarusian State University; and professor at the department of macromolecular compounds, faculty of chemistry, Belarusian State University

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Published
2021-04-09
Keywords: P450, fluorescence, azoles, inhibitors, docking, ciprofioxacin
Supporting Agencies The work was supported by governmental program of scientific researches «Chemical technolo gies and materials» (task No. 2.39; reg. No. 20190221).
How to Cite
Faletrov, Y. V., Glinskaya, L. I., Horetski, M. S., Panada, J. V., Frolova, N. S., & Shkumatov, V. M. (2021). Synthesis of triazole-containing ciprofloxacin conjugate and its in silico test as a cytochrome P450 ligand. Journal of the Belarusian State University. Chemistry, 1, 21-27. https://doi.org/10.33581/2520-257X-2021-1-21-27
Issue
No 1 (2021): Journal of the Belarusian State University. Chemistry
Section
Original Articles

Copyright (c) 2021 Journal of the Belarusian State University. Chemistry

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