Design, Synthesis, and Cytotoxic Analysis of Novel Hederagenin–Pyrazine Derivatives Based on Partial Least Squares Discriminant Analysis

Autor: Wenbo Guo, Xiao-Hua Zhang, Haimin Lei, Yu-Qin Yang, Tao Ma, Xinyu Zhang, Desheng Cai, Kang Fang, Meng Chen, Nan-Nan Xue, Hui Wang, Penglong Wang, Gao-Rong Wu, Yaotian Han
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Pyrazine
Pharmacology
PLS-DA
Catalysis
Article
Inorganic Chemistry
lcsh:Chemistry
03 medical and health sciences
chemistry.chemical_compound
Inhibitory Concentration 50
Structure-Activity Relationship
Cell Line
Tumor
medicine
Cytotoxic T cell
Cluster Analysis
Humans
antitumor activity
Physical and Theoretical Chemistry
Least-Squares Analysis
Oleanolic Acid
Cytotoxicity
Molecular Biology
IC50
Cell Shape
lcsh:QH301-705.5
Spectroscopy
A549 cell
Cisplatin
Principal Component Analysis
Cell Death
Staining and Labeling
Chemistry
Organic Chemistry
Cell Cycle
apoptosis
Discriminant Analysis
General Medicine
hederagenin
Computer Science Applications
Hederagenin
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Cell culture
Drug Design
Pyrazines
pyrazine
medicine.drug
Zdroj: International Journal of Molecular Sciences, Vol 19, Iss 10, p 2994 (2018)
International Journal of Molecular Sciences
Volume 19
Issue 10
ISSN: 1422-0067
Popis: Hederagenin (He) is a novel triterpene template for the development of new antitumor compounds. In this study, 26 new He&ndash
pyrazine derivatives were synthetized in an attempt to develop potent antitumor agents
they were screened for in vitro cytotoxicity against tumor and non-tumor cell lines. The majority of these derivatives showed much stronger cytotoxic activity than He. Remarkably, the most potent was compound 9 (half maximal inhibitory concentration (IC50) was 3.45 ±
0.59 &mu
M), which exhibited similar antitumor activities against A549 (human non-small-cell lung cancer) as the positive drug cisplatin (DDP
IC50 was 3.85 ±
0.63 &mu
M), while it showed lower cytotoxicity on H9c2 (murine heart myoblast
IC50 was 16.69 ±
0.12 &mu
M) cell lines. Compound 9 could induce the early apoptosis and evoke cell-cycle arrest at the synthesis (S) phase of A549 cells. Impressively, we innovatively introduced the method of cluster analysis modeled as partial least squares discriminant analysis (PLS-DA) into the structure&ndash
activity relationship (SAR) evaluation, and SAR confirmed that pyrazine had a profound effect on the antitumor activity of He. The present studies highlight the importance of pyrazine derivatives of He in the discovery and development of novel antitumor agents.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje