New lipophilic conjugates of fluorescent NBD-piperazine: synthesis, in silico interactions with lipid bilayer and cytochromes P450

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 E bind from –14.4 to –10 kcal/mol) and of mycobacteria (2 with sterol 27-hydroxylase CYP125, 3 with “orphan” CYP164; E bind 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.