2. Academic Validation
  3. Anti-chronic myeloid leukemia activity and quantitative structure-activity relationship of novel thiazole aminobenzamide derivatives

Anti-chronic myeloid leukemia activity and quantitative structure-activity relationship of novel thiazole aminobenzamide derivatives

  • Bioorg Med Chem Lett. 2021 Jul 15:44:128116. doi: 10.1016/j.bmcl.2021.128116.
Yuan Zhang 1,  Juan Liu 2,  Xin Wu 3,  Suming Yang 3,  Yao Li 3,  Songbin Liu 3,  Saifei Zhu 3,  Xuan Cao 3,  Zhizhong Xie 3,  Xiaoyong Lei 3,  Honglin Huang 4,  Junmei Peng 5
Affiliations

Affiliations

  • 1 Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang City, PR China; Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang City, Hunan Province 421001, PR China.
  • 2 Department of Pharmacy, Yiyang Central Hospital, Hunan Province 413000, PR China.
  • 3 Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang City, PR China.
  • 4 Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang City, PR China; Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang City, Hunan Province 421001, PR China. Electronic address: 516526281@qq.com.
  • 5 Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang City, PR China; Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang City, Hunan Province 421001, PR China. Electronic address: pengmarina@126.com.
PMID: 34015503 DOI: 10.1016/j.bmcl.2021.128116
Abstract

The anti-chronic myeloid leukemia activity of thiazole aminobenzamide derivatives in vitro was tested by a methanethiosulfonate (MTS)-based viability assay method, and the result showed that some compounds exhibited good inhibitory activities against human chronic myeloid leukemia cell line K562, imatinib-resistant strain K562/R and T135I mutant cell line BaF3-ABL-BCR-T315I. Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) methods were used to analyze the relationship between the structure of thiazole aminobenzamide derivatives and the inhibition of K562/R cell activity. In CoMFA, Q2 was 0.899 and R2 was 0.963; in CoMSIA, Q2 and R2 were 0.840 and 0.903, respectively. These data indicated that the selected test set showed suitable external predictive ability. Combined with the contour map results, we further analyzed the three-dimensional quantitative structure (3D-QSAR) model. The results demonstrated that in the backbone of the thiazole aminobenzamide derivative, the substitution of a small group at R1 position, or the introduction of a hydrophilic group at R2 position, or the introduction of a large-volume amino acid at R3 position may be beneficial to improve the anti-CML activity of the compound.

Keywords

3D QSAR; Cellular activity; CoMFA; CoMSIA; Thiazole aminobenzamide derivatives.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z