Synthesis of Schiff Bases Containing Phenol Rings and Investigation of Their Antioxidant Capacity, Anticholinesterase, Butyrylcholinesterase, and Carbonic Anhydrase Inhibition Properties

Abstract

The widespread usage of Schiff bases in chemistry, industry, medicine, and pharmacy has increased interest in these compounds. Schiff bases and derivative compounds have important bioactive properties. Heterocyclic compounds containing phenol derivative groups in their structure have the potential to capture free radicals that can cause diseases. In this study, we designed and synthesized eight Schiff bases (10–15) and hydrazineylidene derivatives (16–17), which contain phenol moieties and have the potential to be used as synthetic antioxidants, for the first time using microwave energy. Additionally, the antioxidant effects of Schiff bases (10–15) and hydrazineylidene derivatives (16–17) were studied using by the bioanalytical methods of 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) cation radical (ABTS•+) and 1,1-diphenyl-2-picrylhydrazyl (DPPH•) scavenging activities, and Fe3+, Cu2+, and Fe3+-TPTZ complex reducing capacities. In the context of studies on antioxidants, Schiff bases (10–15) and hydrazineylidene derivatives (16–17) were found to be as powerful DPPH (IC50: 12.15–99.01 μg/mL) and ABTS•+ (IC50: 4.30–34.65 μg/mL). Additionally, the inhibition abilities of Schiff bases (10–15) and hydrazineylidene derivatives (16–17) were determined towards some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I and II (hCAs I and II), enzymes that are linked to some global disorders including Alzheimer’s disease (AD), epilepsy, and glaucoma. In the context of studies on enzyme inhibition, it was observed that the synthesized Schiff bases (10–15) and hydrazineylidene derivatives (16–17) inhibited AChE, BChE, hCAs I, and hCA II enzymes with IC50 values in ranges of 16.11–57.75 nM, 19.80–53.31 nM, 26.08 ± 8.53 nM, and 85.79 ± 24.80 nM, respectively. In addition, in light of the results obtained, we hope that this study will be useful and guiding for the evaluation of biological activities in the fields of the food, medical, and pharmaceutical industries in the future.

Investigation of the effects of some pesticides on carbonic anhydrase isoenzymes

“…The reaction of CA with CO 2 produces H + and HCO 3 − ions. This reaction occurs in many tissues, such as kidney, gastric mucosa, and lens of the eye 35–37 …”

“…This reaction occurs in many tissues, such as kidney, gastric mucosa, and lens of the eye. [35][36][37] In this study, two CA isozymes were purified in a single step by Sepharose-4B-4-(6-amino-hexyloxy)-benzenesulfonamide affinity column chromatography. hCA I was purified 95.53-fold with a specific activity of 709.09 EU/mg and an overall yield of 70.91%, and hCA II was purified 215.56-fold with a specific activity of 1600 EU/mg and an overall yield of 52.36% (Table 2).…”

Lavandula stoechas L. subsp. stoechas, a New Herbal Source for Ursolic Acid: Quantitative Analysis, Purification and Bioactivity Studies

“…Carbonic anhydrase inhibitors have therapeutic uses in the treatment of infections, convulsions, glaucoma, and cancer. In addition, high intraocular pressure due to glaucoma can be alleviated by using carbonic anhydrase inhibitors [40–41] . Cholinesterase enzymes are activity parameters thought to be part of prophylaxis to treat neurological disorders associated with Alzheimer's disease.…”

“…In addition, high intraocular pressure due to glaucoma can be alleviated by using carbonic anhydrase inhibitors. [40][41] Cholinesterase enzymes are activity parameters thought to be part of prophylaxis to treat neurological disorders associated with Alzheimer's disease. Cholinesterase inhibition is one of the most important strategies used in the treatment of Alzheimer's disease.…”

Design, synthesis, and molecular docking studies of benzimidazole‐1,3,4‐triazole hybrids as carbonic anhydrase I and II inhibitors

“…Antioxidants reduce the production of free radicals, shielding living things from the harmful effects of ROS. Additionally, it has been suggested that ROS and free radicals have a role in a number of serious illnesses that affect people all over the world, including cancer, atherosclerosis, rheumatoid arthritis, neurodegenerative, autoimmune, cardiovascular, and age‐related diseases (Aytac et al, 2023). It is thought that the synthesized compounds showing both carbonic anhydrase and antioxidant properties will provide an advantage in the treatment of diseases for which ROS, free radicals, and carbonic anhydrases are responsible.…”