New lipophilic conjugates of fluorescent NBD-piperazine: synthesis, in silico interactions with lipid bilayer and cytochromes P450
https://doi.org/10.29235/1561-8331-2022-58-1-62-67
Abstract
Two new fluorescent NBD-piperazine derivatives with lipophilic substituents of formylcholesterol and hexanoic acid (compounds 2 and 3, respectively) were synthesized. Using in silico calculations, their abilities to permeate through lipid bilayer and to be bound affinely with some cytochromes P450 of human (2 with lanosterol 14α-demethylase CYP51, 3 with drug-metabolizing CYP1A1, CYP2D6, CYP3A4; energy of binding Ebind from –14.4 to –10 kcal/mol) and of mycobacteria (2 with sterol 27-hydroxylase CYP125, 3 with “orphan” CYP164; Ebind from –13.3 to –9.1 kcal/mol) were demonstrated. The synthesized compounds and calculated computational data will contribute to prioritization of in vitro investigations aiming to revealing properties of the proteins.
About the Authors
Y. V. Faletrov
Belarusian State University;
Research Institute for Physical Chemical Problems of the Belarusian State University
Belarus
Belarus
Faletrov Yaroslav V. – Ph. D. (Chemistry), Associate Professor, Leading Researcher. Research Institute for Physical Chemical Problems of the Belarusian State University
14, Leningradskaya Str., 220006, Minsk
H. I. Pozniak
Belarusian State University
Belarus
Belarus
Pozniak Hleb I. – 4-year student of the Faculty of Chemistry
14, Leningradskaya Str., 220006, Minsk
P. S. Yakovets
Belarusian State University
Belarus
Belarus
Yakovets Polina S. – 5-year student of the Faculty of Chemistry
14, Leningradskaya Str., 220006, Minsk
N. S. Frolova
Belarusian State University;
Research Institute for Physical Chemical Problems of the Belarusian State University
Belarus
Belarus
Frolova Nina S. – Researcher. Research Institute for Physical-Chemical Problems of the Belarusian State University
14, Leningradskaya Str., 220006, Minsk
V. M. Shkumatov
Belarusian State University;
Research Institute for Physical Chemical Problems of the Belarusian State University
Belarus
Belarus
Shkumatov Vladimir M.– Corresponding Member of the National Academy of Sciences of Belarus, D. Sc. (Biology), Professor, Head of the Laboratory. Research Institute for Physical-Chemical Problems of the Belarusian State University
14, Leningradskaya Str., 220006, Minsk
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