Inhibition Effects of Some Non‐Proteinogenic Amino Acid Derivatives on Carbonic Anhydrase Isoenzymes and Acetylcholinesterase: An In Vitro Inhibition and Molecular Modeling Studies

• Published in: Chemistry & biodiversity 2024-12, Vol.21 (12), p.e202401225-n/a
• Main Authors: Alım, Zuhal, Rawat, Ravi, Adem, Şevki, Eyüpoğlu, Volkan, Akkemik, Ebru
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Acetylcholinesterase - metabolism; Amino acids; Amino Acids - chemistry; Amino Acids - metabolism; Amino Acids - pharmacology; Carbonic anhydrase; Carbonic anhydrase I; Carbonic Anhydrase I - antagonists & inhibitors; Carbonic Anhydrase I - metabolism; Carbonic Anhydrase II - antagonists & inhibitors; Carbonic Anhydrase II - metabolism; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Carbonic Anhydrases - metabolism; Chemical properties; Chemical synthesis; Cholinesterase inhibitors; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Dose-Response Relationship, Drug; Drug development; Enzyme inhibition; Glaucoma; Health services; Hippuric acid; Humans; Inhibitors; Isoenzymes; Isoenzymes - antagonists & inhibitors; Isoenzymes - metabolism; Methylamine; Modelling; Models, Molecular; Molecular docking; Molecular Docking Simulation; Molecular modelling; Molecular Structure; Phenethylamine; Phenylethylamine; Structure-Activity Relationship; Valine
• ISSN: 1612-1872; 1612-1880; 1612-1880
• DOI: 10.1002/cbdv.202401225

Amino acid derivatives are molecules of interest for medicinal chemistry and drug design studies due to their important chemical properties. In this study, the inhibition effects of some non‐proteinogenic amino acid derivatives (hippuric acid (A), N‐(9‐Fluorenylmethoxycarbonyl)‐D‐valine (B), N‐Z‐(1‐Benzotriazolylcarbonyl) methylamine (C), (S)‐N‐Z‐1‐Benzotriazolylcarbonyl‐2‐phenylethylamine (D)) on carbonic anhydrase I (hCA‐I), II (hCA‐II) isoenzymes and acetylcholinesterase (AChE) activity, whose inhibitors are of vital pharmacological importance, were examined. While carbonic anhydrase (CA) inhibitors are effective molecule candidates for the treatment of many diseases from glaucoma to cancer, acetylcholinesterase inhibitors are target molecules for the treatment of Alzheimer′s disease. According to the results of this study, compound D had a strong inhibitory effect on hCA‐I (IC50: 0.836 μM) and hCA‐II (IC50: 0.661 μM), while compound B (IC50: 100 μM) showed a strong inhibitory effect on AChE activity. In addition, inhibition results were supported by molecular modeling studies. We hope that the obtained results will contribute to the synthesis of new and effective amino acid derivative inhibitors for CA and AChE.