A safe alternative synthesis of primary carbamates from alcohols; <i>in vitro</i> and <i>in silico</i> assessments as an alternative acetylcholinesterase inhibitors

Carbamates are important molecules because they are used in various biochemical processes. In this study, effective alternative method for the synthesis of primary carbamates from alcohols was developed in the presence of chlorosulfonyl isocyanate (CSI) in pyridine at room temperature in mild conditions. The primary carbamates were synthesized excellent yield. This method is easy, practical, and inexpensive without any additive, metal, or catalyst. Alzheimer's disease (AD) is a neurodegenerative disease and has been reported to affect approximately 50 million people worldwide in 2020. Drugs that reversibly inhibit the acetylcholinesterase (AChE) activity are used for the treatment of AD. For this reason, there is a growing interest in developing alternative AChE inhibitors. Concordantly, Anti-anticholinesterase activity of synthesized carbamate derivatives was investigated as an alternative AChE inhibitors. In order to determine the inhibitory effect of these molecules, IC50, and K-i values and inhibition types were determined. According to the K-i results, the most effective inhibitors were 3 b and 3e with the K-i values of 22 and 38 mu M, respectively. It was found that all molecules showed competitive inhibition type. For clarify the inhibitors-enzyme interactions, molecular docking studies were performed and possible binding interactions between the synthesized molecules and AChE were determined. Additionally, the pharmacokinetic and properties of the synthesized molecules were evaluated in silico. Communicated by Ramaswamy H. Sarma.

Dergi

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS

Yıl

2023

Cilt

41

Sayı

17

Sayfa

8191-8200

ISSN

0739-1102

eISSN

1538-0254

DOI

10.1080/07391102.2022.2134209

WoS UID

WOS:000866274200001