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

• Published in: Journal of molecular structure 2023-02, Vol.1273, p.134313, Article 134313
• Main Authors: Kawka, Anna, Hajdaś, Grzegorz, Kułaga, Damian, Koenig, Hanna, Kowalczyk, Iwona, Pospieszny, Tomasz
• Format: Article
• Language: English
• Subjects: 1,2,3-triazole ring; Bile acids; Click chemistry; Molecular docking; PASS; Semiempirical calculations; Sterols
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.134313

•Six novel bile acid–sterol conjugates linked with a 1,2,3-triazole ring were synthesized.•1H NMR, 13C NMR, FT-IR and ESI-MS were performed for the characterization.•Computational study was done at PM5 method level for comparative analysis.•In silico study was done to facilitate the search for pharmacological activity. New six steroid conjugates have been prepared from bile acids (tail part)and sterol (head part) derivatives 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. Previously, 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 propargyl esters of deoxycholic and cholic acids as well as 5α-cholestan-3-yl-propynoatewere also obtained and characterized for the first time. All conjugates were obtained in good yields using an efficient synthesis method. The structures of all conjugates as well as four substrates were confirmed by spectral (1H- and 13C 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 13C and 1H 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 Substances (PASS). Additionally molecular docking was performed for the selected conjugate.