Structure—hemolytic activity relationship in isobornylphenol derivatives

Synthesis and Antioxidant Ability of Novel Derivatives Based on para‐Coumaric Acid Containing Isobornyl Groups

“…Novel para ‐coumaric acid derivatives were synthesized from 2,6‐diisobornyl‐4‐methylphenol ( 1 ), which is a close analog of the known antioxidant 2,6‐di‐ tert ‐butyl‐4‐methylphenol (BHT) and has terpene fragments with isobornyl (bicyclo[2.2.1]heptane) structure instead of tert ‐butyl groups. As shown previously, compound 1 exhibits AO properties in vitro, surpassing the activity of BHT by a number of parameters, and is characterized by low hemolytic efficiency . During the experiments on laboratory animals, compound 1 showed rheologic activity in ischemia/reperfusion conditions and cardioprotective properties .…”

“…All specified compounds significantly surpassed the known antioxidant BHT, whereas amide 10 was not inferior to starter 2,6‐diisobornyl‐4‐methylphenol ( 1 ) and completely prevented the hemolysis of RBCs under the influence of H 2 O 2 . We repeatedly observed an enhancement of AOA with the introduction of the morpholine fragment in aminomethyl and amidomethyl derivatives of phenolic compounds in various in vitro models . It is known that the introduction of a substituent for this heterocyclic amine is used in the design of new pharmacological substances, including those with AOA .…”

“…We have previously noted that phenolic compounds containing a free carboxy group in their structures at a concentration of≥10 μ m have exhibited high hemolytic efficiency . Acids 3 and 11 were no exception in this regard, as after their introduction at a concentration of 10 μ m into the incubation medium, the level of hemolysis after 5 h was 94.0±0.3 % and 20.3±1.1 %, respectively.…”

“…For compounds 3 – 10 , radical‐scavenging activity (RSA) was evaluated along with 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH); AO activity (AOA) on a substrate containing the lipids of animal brain, hemolytic efficiency (cytotoxicity of red blood cells (RBCs)), and their AO and membrane‐protective (MP) properties were evaluated on the model of oxidative RBCs hemolysis. We have previously used the test systems listed above in the course of a systematic study of the activity of various classes of phenolic compounds . BHT, 2,6‐diisobornyl‐4‐methylphenol ( 1 ), as well as 4‐hydroxy‐3,5‐diisobornylbenzoic acid ( 11 ) synthesized earlier and its derivatives 12 and 13 were used as reference compounds ( Figure ).…”

“…A further study of the MP activity (MPA) of all compounds based on RBCs was carried out at a concentration of 1 μ m , as it is known that reduction of concentration or substitution of the hydrogen atom in the carboxy fragment allows to minimize hemolytic efficiency . An evaluation of MPA demonstrated that almost all compounds exhibited a statistically significant increase of cell survival under H 2 O 2 ‐oxidative stress conditions during the entire incubation period ( Figure ).…”