Synthesis, Hemolytic Activity, and In Silico Studies of New Bile Acid Dimers Connected with a 1,2,3-Triazole Ring

• Published in: ACS omega 2024-09, Vol.9 (37), p.39277-39286
• Main Authors: Hajdaś, Grzegorz, Kułaga, Damian, Koenig, Hanna, Sosnowska, Katarzyna, Mrówczyńska, Lucyna, Pospieszny, Tomasz
• Format: Article
• Language: English
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.4c07103

The synthesis of bile acid conjugates plays a significant role in pharmacology and organic chemistry. These complex compounds are widely studied due to their potential therapeutic applications (e.g., drug carriers or antibacterial agents) and their impact on interactions with biological target systems. It is important to determine the biological activity of the obtained conjugates with potential pharmacological applications. The research aimed to synthesize acyl conjugates of bile acids, determine the influence of acyl groups on potential antibacterial activity and evaluate the impact of conjugation on hemolytic activity. New acetyl bile acid acetyl dimers were synthesized using the “Click Chemistry” reaction, aiming to investigate their hemolytic and antibacterial activity. The structures of all compounds were confirmed through spectral analysis techniques, including 1H and 13C nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), and electrospray ionization-mass spectrometry (ESI-MS). The PM5 semiempirical method was also used to estimate the heat of formation of individual conjugates, and the prediction of activity spectra for substances (PASS) technique was used to determine the pharmacokinetic potential of compounds. Docking studies indicate that obtained conjugates have the potential ability to inhibit the biosynthesis of Lipid II and block DNA gyrase. These compounds can therefore be treated as potential candidates for antibacterial compounds. Research findings suggest that conjugating bile acids and their derivatives through 1,2,3-triazole ring, results in final products with reduced hemolytic activity.