3D-QSAR Studies on New Benzothiazole-Based Dual Functional Inhibitors of BCR-ABL Kinase Including the T315I Mutant

Title:3D-QSAR Studies on New Benzothiazole-Based Dual Functional Inhibitors of BCR-ABL Kinase Including the T315I Mutant

Volume: 15 Issue: 10

Author(s): Shunlai Li, Chaorui Ren, Chenghu Lu, Xiuxiu Li and Hongguang Du*

Affiliation:

• College of Science, Beijing University of Chemical Technology, Beijing,China

Keywords: Tyrosine kinase inhibitors, CML, benzothiazole-based inhibitors, 3D-QSAR, SOMFA, T315I mutant.

Abstract: Background: Chronic Myelogenous Leukemia (CML) is a kind of blood and bone marrow cancer. Tyrosine Kinase Inhibitors (TKIs) play an important role in the treatment of Chronic Myelogenous Leukemia (CML).

Objective: The aims of this study are to demonstrate the different binding mode of Benzothiazole- Based analogues with T315I mutant Bcr-Abl and wild-type Bcr-Abl.

Methods: In this paper, Self-Organizing Molecular Field Analysis (SOMFA), a simple Three- Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) analysis was performed on these 49 benzothiazole-based derivatives.

Results: In this paper, highly predictive SOMFA models ( r2 = 0.748, rcv 2 = 0.720, F value = 124.9, and SEE = 0.761 for T315I mutant Bcr-Abl, r2 = 0.676, rcv 2 = 0.616, F value = 52.98, and SEE = 0.767 for wild-type Bcr-Abl) were obtained, and the generated models were validated using test sets.

Conclusion: We obtained the best models of the training set and the statistical results for SOMFA model had a high predictive ability. The contour maps of potent compounds 9b was constructed by SOMFA method and some useful information was obtained for further designing new structures with high activity.

Cite this article as:

Li Shunlai , Ren Chaorui , Lu Chenghu , Li Xiuxiu and Du Hongguang *, 3D-QSAR Studies on New Benzothiazole-Based Dual Functional Inhibitors of BCR-ABL Kinase Including the T315I Mutant, Letters in Drug Design & Discovery 2018; 15 (10) . https://dx.doi.org/10.2174/1570180815666180105163053