Naslov
Coumarin derivatives as inhibitors of acetylcholinesterase: QSAR study

Autori
Šubarić, Domagoj ; Agić, Dejan ; Bešlo, Drago ; Karnaš, Maja ; Molnar, Maja ; Rastija, Vesna

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
23rd European Symposium on Quantitative Structure- Activity Relationship, Integrative Data-Intensive Approaches to Drug Design, Book of Abstracts / - , 2022, 139-139

Skup
23rd European Symposium on Quantitative Structure- Activity Relationship, Integrative Data-Intensive Approaches to Drug Design

Mjesto i datum
Heidelberg, Njemačka, 26-30.09.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Coumarine derivatives ; QSAR ; inhibition

Sažetak
Coumarin and its derivatives are well-known phytochemicals that have shown great potential in acetylcholinesterase (AChE) inhibition [1]. Novel coumarin derivatives have been tested as acethylcholinesterase (AChE) inhibitors by utilizing the Ellman's method [2]. Inhibition data were expressed as a logarithm of inhibition percentages. Molecular structures were optimized by PM3 method using Hyperchem software. Molecular descriptors have been calculated by ADMEWORKS ModelBuilder software. QSAR analysis for inhibition of AChE was performed on the 34 compounds in the training set. Due to the small number of compounds, they were not split in training and test sets. The best QSAR model obtained is: log inh.% = - 1.09 – 0.11 MATS7m + 1.84 MCB + 0.17 DIPZ (1) where MATS7m is Moran autocorrelation of lag 7, weighted by atomic masses ; MCB is Balabans topological index, and DIPZ is dipole moment on Z axes. The model has achieved the following statistical performance of the internal validation: R2 = 0.78 ; F = 37.26 ; Δk = 0.23 ; CCCtr = 0.88 ; CCCcv = 0.84 ; Q2loo = 0.71 ; Q2γscr = -0.18. Williams plot for applicability domain of model (1) is shown in Figure 1. Molecular descriptors in model (1) revealed that effect of inhibition of molecules decreased with: lower number of atoms higher mass at spatial lag 7, increasing branching, and small difference in electronegativity between two bonded atoms at the Z axes.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Interdisciplinarne prirodne znanosti

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