Neural Network Modeling of AChE Inhibition by New Carbazole-Bearing Oxazolones

Abstract

Acetylcholine esterase (AChE) is one of the targeted enzymes in the therapy of important neurodegenerative diseases such as Alzheimer's disease. Many studies on carbazole- and oxazolone-based compounds have been conducted in the last decade due to the importance of these compounds. New carbazole-bearing oxazolones were synthesized from several carbazole aldehydes and p-nitrobenzoyl glycine as AChE inhibitors by the Erlenmeyer reaction in the present study. The inhibitory effects of three carbazole-bearing oxazolone derivatives on AChE were studied in vitro and the experimental results were modeled using artificial neural network (ANN). The developed ANN provided sufficient correlation between several dependent systems, including enzyme inhibition. The inhibition data for AChE were modeled by a two-layered ANN architecture. High correlation coefficients were observed between the experimental and predicted ANN results. Synthesized carbazole-bearing oxazolone derivatives inhibited AChE under in vitro conditions, and further research involving in vivo studies is recommended. An ANN may be a useful alternative modeling approach for enzyme inhibition.

Artificial intelligence and machine learning‐aided drug discovery in central nervous system diseases: State‐of‐the‐arts and future directions

“…Researchers have built ML models—SVM, ANN, and RF—to predict the inhibitory effect of compounds against AD‐related proteins—histone deacetylase (HDAC), 415 acetylcholinesterase (AChE), 416 and S100 calcium‐binding protein A9 (S100A9), 417 respectively. Although these target‐specific models were successful for predicting the bioactive compounds, a high level of reliability is necessary for prioritizing compounds that are ultimately translated into assays.…”

Inhibitory Activity of 4-Benzylidene Oxazolones Derivatives of Cinnamic Acid on Human Acetylcholinesterase and Cognitive Improvements in a Mouse Model

“…There are no reports in the literature on the inhibitory activity of oxazolones on hAChE; however, Cavas et.al., synthesized new carbazole-bearing oxazolones and studied the inhibitory activity in vitro on AChE from Electrophorus electricus (EC 3.1.1.7), and the experimental results were modeled using artificial neural network techniques. Oxazolone derivatives inhibited AChE under in vitro conditions, and the authors recommend further investigation with in vitro and vivo studies [5]. Due the importance of these compounds in the present study, we report the synthesis, characterization (see supplementary information), and hAChE inhibition properties of a series of oxazolones derivatives from cinnamic acid.…”

“…As one of the premier biological catalysts, it accelerates the hydrolysis of the neurotransmitter acetylcholine by an estimated 13 orders of magnitude [4]. Human acetylcholinesterase (hAChE) (3.1.1.7) consists of a central 12-stranded mixed β-sheet surrounded by 14 α-helices [5]. The enzyme structure contains three key features: the active catalytic site (CAS), the gorge, and the peripheral anionic site (PAS).…”

Highly Diastereo‐ and Enantioselective Aza‐Mannich Addition of Oxazolones to N‐Boc Protected α‐Amido Sulfones Catalyzed by Bifunctional Thiourea‐modified Cinchona Alkaloid

“…Over the last few years, azlactone core which makes a prominent structure of number of well-established marked drugs such as rilmenidine, furazolidone etc has attracted considerable attention of the medicinal chemistry community for the biological activities such as anticancer, [1] antidiabetic, [2] antimicrobial, [3] analgesic, [4] anti-inflammatory, [5] muscle relaxant, [6] neuroleptic, [7] antitubercular, [8] antiangiogenic, [9] immunomodulator, [10] cardiotonic, [11] cyclooxygenase-2 inhibitor, [12] Acetylcholine esterase inhibitor, [13] and tyrosinase inhibitor, [14] etc. In addition, these azlactone derivatives have been used in order to produce different kinds of polymers and nanomaterials which presented great development in the last decade.…”