Evaluation of antioxidant potentials and acetylcholinesterase inhibitory effects of some new salicylic acid-salicylamide hybrids

• Published in: Journal of the Iranian Chemical Society 2023-07, Vol.20 (7), p.1535-1543
• Main Authors: Koca, Mehmet, Gülçin, İlhami, Üç, Eda Mehtap, Bilginer, Sinan, Aydın, Amine Sena
• Format: Article
• Language: English
• Subjects: Acids; Alzheimer's disease; Analytical Chemistry; Antioxidants; Benzoic acid; Biochemistry; Chemical synthesis; Chemistry; Chemistry and Materials Science; Cholinergics; Cosmetics; Cupric ions; Ferric ions; Inorganic Chemistry; Molecular docking; NMR; Nuclear magnetic resonance; Organic Chemistry; Original Paper; Oxidation; Physical Chemistry; Radicals; Salicylic acid; Scavenging; Sulfonic acid
• ISSN: 1735-207X; 1735-2428
• DOI: 10.1007/s13738-023-02775-0

Antioxidants are used in foods, drugs, and many products such as cosmetics to prevent the formation of toxic radicals resulting from oxidation. It is thought that the antioxidant potentials of AChE inhibitors will contribute positively to the treatment of Alzheimer's disease (AD). In this study, firstly, hybrid molecule 2-hydroxy-4-(2-hydroxybenzamido)benzoic acid consisting of salicylic acid and salicyl amide structures, which has been previously reported in the literature, was synthesized. Then, five new amide derivatives (2-hydroxy-4-(2-hydroxybenzamido)-N-methyl/ethyl/ethyl/diethyl/isopropyl benzamides) of 2-hydroxy-4-(2-hydroxybenzamido)benzoic acid were synthesized (for the first time). The structures of all synthesized compounds were confirmed by 1 H-NMR and 13 C-NMR spectra and Q-TOF. Antioxidant potentials of the compounds were evaluated by 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical (ABTS ·+ ) scavenging assay and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH · ) scavenging assay. As an example to state the results, the synthesized salicylic acid-salicylamide hybrid derivatives (1–6) displayed IC 50 values between 40.76 and 49.50 µg/mL for DPPH · ) scavenging ability. The reducing ability of the compounds was measured by cupric ions (Cu 2+ ) reducing (CUPRAC) ability, and ferric ions (Fe 3+ ) and [Fe 3+ -(TPTZ)2] 3+ complex reducing (FRAP) abilities. The compounds were screened for AChE inhibitory activity to find out new possible drug candidate molecules. Newly synthesized salicylic acid-salicylamide hybrids (1–6) inhibited cholinergic AChE (%) inhibitory ability in the ranging of 6 ± 2 and 54 ± 3 at 100 µg/mL concentration. It was determined that compound 5 had the most AChE inhibitory potential among the synthesized compounds. Also, possible interactions between compound 5 and the active sites of the enzyme were investigated by molecular docking studies. Antioxidant tests and AChE inhibition effects were investigated in order to evaluate the antioxidant potentials of newly synthesized compounds for synthetic antioxidants, which are frequently used in the food and pharmaceutical industries, and to investigate their potential as a drug against Alzheimer's disease. Graphical Abstract