QSAR Studies on a Series of Pyrazole Azabicyclo [3.2.1] Octane Sulfonamides N-acylethanolamine-hydrolyzing Acid Amidase Inhibitors

Title:QSAR Studies on a Series of Pyrazole Azabicyclo [3.2.1] Octane Sulfonamides N-acylethanolamine-hydrolyzing Acid Amidase Inhibitors

Volume: 21 Issue: 9

Author(s): Shengnan Ren, Liyang Sun, Hongzong Si, Zhuang Yu and Huan Wang*

Affiliation:

• Department of Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong, 266035, China

Keywords: NAAA inhibitor, anti-inflammatory, quantitative structure-activity relationship, model, gene expression programming, heuristic method.

Abstract:

Background: Inflammation is a common and intractable disease for humans. Current antiinflammatory drugs have a lot of side effects, which cause irreversible damage to the body.

Objective: We predict the activity of the N-acylethanolamine-hydrolyzing acid amidase (NAAA) inhibitor to find more effective compounds.

Methods: we established a quantitative structure-activity relationship (QSAR) model by gene expression programming to predict the IC₅₀ values of natural compounds. The NAAA inhibitor, as a cysteine enzyme, plays an important role in the therapy of pain, anti-inflammatory effects and application of other diseases. A total of 36 NAAA inhibitors were optimized by the heuristic method in the CODESSA program to build a linear model. The 27 compounds and 9 compounds were in train and test sets. On this basis, we selected three descriptors and used them to build nonlinear models in gene expression programming.

Results: The best model in the gene expression programming method was found, the square of correlation coefficients of R² and mean square error for the training set were 0.79 and 0.14, testing set was 0.78 and 0.20, respectively.

Conclusion: From this method, the activity of molecules could be predicted, and the best method was found. Therefore, this model has a stronger predictive ability to develop NAAA inhibitors.

Cite this article as:

Ren Shengnan, Sun Liyang, Si Hongzong, Yu Zhuang and Wang Huan*, QSAR Studies on a Series of Pyrazole Azabicyclo [3.2.1] Octane Sulfonamides N-acylethanolamine-hydrolyzing Acid Amidase Inhibitors, Letters in Drug Design & Discovery 2024; 21 (9) . https://dx.doi.org/10.2174/1570180820666230418093238