Synthesis and Inhibitor Effect Novel Alkoxymethyl Derivatives of Dihetero Cycloalkanes on Carbonic Anhydrase and Acetylcholinesterase

Vagif Farzaliyev; Adem Ertürk; Malahat Abbasova; Oruj Nabiyev; Yeliz Demir; Hatice Kızıltaş; Afsun Sujayev; İlhami Gülçin

doi:10.1002/cbdv.202400296

Synthesis and Inhibitor Effect Novel Alkoxymethyl Derivatives of Dihetero Cycloalkanes on Carbonic Anhydrase and Acetylcholinesterase

Chem Biodivers. 2024 Apr 4:e202400296. doi: 10.1002/cbdv.202400296. Online ahead of print.

Authors

Vagif Farzaliyev^{1

2}, Adem Ertürk³, Malahat Abbasova¹, Oruj Nabiyev¹, Yeliz Demir⁴, Hatice Kızıltaş⁵, Afsun Sujayev¹, İlhami Gülçin³

Affiliations

¹ Institute of Chemistry of Additives, Ministry of Science and Education of the Republic of Azerbaijan, 1029, Baku, Azerbaijan.
² Baku State University, Z. Khalilov Str. 23, AZ-1148, Baku, Azerbaijan.
³ Ataturk University, Faculty of Science, Department of Chemistry, 25240, Erzurum, Türkiye.
⁴ Ardahan University, Nihat Delibalta Göle Vocational High School, Department of Pharmacy Services, 75700, Ardahan, Türkiye.
⁵ Van Yüzüncü Yıl University, Van Vocational School of Health Services, 65080, Van, Türkiye.

PMID: 38575390
DOI: 10.1002/cbdv.202400296

Abstract

1,3-Diheterocycloalkanes derivatives are important starting materials in fine organic synthesis. These compounds can be widely used in various fields such as industry, medicine, biotechnology and chemical technology. The paper is focused on synthesis and study of alkoxymethyl derivatives of diheterocycloalkanes (M1-M15) and inhibition effect on carbonic anhydrase and acetylcholinesterase. The structures of compounds were confirmed by ¹H and ¹³C NMR spectroscopy. Also, in this study alkoxymethyl derivatives of diheterocycloalkanes were assessed for their influence on various metabolic enzymes, including acetylcholinesterase (AChE) and human carbonic anhydrase isoenzymes (hCA I and hCA II). The results demonstrated that all these compounds exhibited potent inhibitory effects on all the target enzymes, surpassing the standard inhibitors, as evidenced by their IC₅₀ and K_i values. The K_i values for the compounds concerning AChE, hCA I, and hCA II enzymes were in the ranges of 1.02±0.17-8.38±1.02, 15.30±3.15-58.14±5.17 and 24.05±3.70-312.94±27.24 nM, respectively.

Keywords: 1,3-imidazolidine; 1,3-oxazine; 1,3-oxazolidine; acetylcholinesterase; benzothiazol-2-thione; carbonic anhydrase; enzyme inhibition.