Haemolytic activity of formyl- and acetyl-derivatives of bile acids and their gramine salts

Synthesis and Hemolytic Activity of Bile Acid-Indole Bioconjugates Linked by Triazole

“…The effect of structural modifications of bile acid molecules on their ability to incorporate into cell membranes was investigated using red blood cells (RBCs) as a model. , Our previous study has shown that at a concentration of 0.1 mg/mL, the formyl modification of bile acids increases their hemolytic activity, especially in the case of noncytotoxic cholic acid. The hemolytic activity of acetyl-LCA and DCA was significantly higher than their native forms, whereas the acetyl-CA was not active as membrane perturbing agents at the same concentration …”

“…As mentioned before, as amphiphilic compounds, bile acids interact easily with the lipid bilayer of RBC and modify RBC shape from dysocytic to echinocytic or stomatocytic, depending on their chemical structure and concentration used . As shown in Figure , after incubation with derivatives 10 and 17 , the RBC shape is dyscocytic.…”

“…As mentioned before, as amphiphilic compounds, bile acids interact easily with the lipid bilayer of RBC and modify RBC shape from dysocytic to echinocytic or stomatocytic, depending on their chemical structure and concentration used. 36 As shown in Figure 7, after incubation with derivatives 10 and 17, the RBC shape is dyscocytic. Therefore, structural modification of bile acid formyl derivatives by introducing indole and 1,2,3triazole moieties modifies their interaction with the RBC membrane and consequently does not affect the discocytic 8) could be formed between the ligand and the protein domain.…”

“…The hemolytic activity of acetyl-LCA and DCA was significantly higher than their native forms, whereas the acetyl-CA was not active as membrane perturbing agents at the same concentration. 36 As shown in Figure 5, the hemolytic activity (%) of all synthesized formyl derivatives of bile acids propargyl esters (8−11) and their bioconjugates with modified gramine molecules linked with 1,2,3-triazole ring (15−18), is significantly decreased (in the range of 2.36−13.87%) in comparison with formyl derivatives (F-LCA, F-DCA, and F-CA in the range of 94−99%). Similarly, acetyl derivatives of bile acid propargyl esters (12−13) and their triazole bioconjugates (19−20) are less cytotoxic (3.36−8.26%) than acetylated bile acids (Ac-LCA, Ac-DCA�97−98%).…”

“…The molecular mechanism of interaction between bile acids molecules and the cell membrane, as well as the hemolysis type, is dependent on the protonation of the anionic group of bile acids. 34,35 Based on the fact that the hemolytic activity of bile acids and their formyl and acetyl derivatives can be reduced or eliminated by the introduction of gramine, 36 the newly synthesized compounds have also been evaluated for their hemolytic potency.…”