Molecular structure, spectral and theoretical study of new type bile acid-sterol conjugates linked via 1,2,3-triazole ring

New six steroid conjugates have been prepared from bile acids (tail part)and sterol (head part) deriva-tives using click chemistry method. The azide-alkyne Huisgen cycloaddition (intermolecular 1,3-dipolar cycloaddition) of the azide derivatives of lithocholic, deoxycholic, cholic acid and propiolate ester of cholesterol and cholestanol gave a new bile acid-sterol conjugates linked with a 1,2,3-triazole ring. Pre-viously, bile acids were converted into bromoacetyl substituted derivatives by the reaction of propargyl esters of lithocholic, deoxycholic, cholic with bromoacetic acid bromide in toluene with TEBA and sodium hydride. Additionally, five of the reagents: bromoacetyl and azidoacetyl substituted derivatives of propar-gyl esters of deoxycholic and cholic acids as well as 5 alpha-cholestan-3-yl-propynoatewere also obtained and characterized for the first time. All conjugates were obtained in good yields using an efficient synthe-sis method. The structures of all conjugates as well as four substrates were confirmed by spectral ( 1 H -and 13 C NMR, and FT-IR) analysis, mass spectrometry (ESI-MS), as well as PM5 semiempirical methods. Also B3LYP calculations have been carried out. The screening constants for 13 C and 1 H atoms have been calculated by the GIAO/B3LYP/6-311G(d,p) approach and analyzed. Theoretical vibrational parameters are compared with obtained experimental parameters. Estimation of the pharmacotherapeutic potential has been accomplished for the synthesized compounds on the basis of Prediction of Activity Spectra for Sub-stances (PASS). Additionally molecular docking was performed for the selected conjugate. (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Automated summary

New steroid conjugates were synthesized by click chemistry method using bile acids and sterol derivatives. The conjugates were obtained by azide-alkyne cycloaddition reaction, forming a bile acid-sterol conjugate linked with a 1,2,3-triazole ring. The structures of the conjugates and substrates were confirmed by spectral analysis, mass spectrometry, and computational calculations. The synthesized compounds were evaluated for their pharmacotherapeutic potential using prediction of activity spectra and molecular docking.