Naturally based pyrazoline derivatives as aminopeptidase N, VEGFR2 and MMP9 inhibitors: design, synthesis and molecular modeling

被引:1
|
作者
Batran, Rasha Z. [1 ]
Ahmed, Eman Y. [1 ]
Awad, Hanem M. [2 ]
Latif, Nehad A. Abdel [1 ]
机构
[1] Natl Res Ctr, Pharmaceut & Drug Ind Res Inst, Chem Nat Cpds Dept, Cairo 12622, Egypt
[2] Natl Res Ctr, Tanning Mat & Leather Technol Dept, Cairo 12622, Egypt
关键词
ANTICANCER ACTIVITY; INVASION; DOCKING; CANCER; CHARMM;
D O I
10.1039/d4ra01801j
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Aminopeptidase N (APN) is regarded as an attractive target for cancer treatment due to its overexpression in various types of malignancies and its close association with cancer angiogenesis, metastasis and invasion. Herein the authors describe the design, synthesis and biological evaluation of some naturally based pyrazoline derivatives. Among these compounds, the diphenylpyrazole carbothioamide 8 showed significant activity and selectivity index (SI = 4.7) on breast (MCF-7) human cancer cell line and was capable of inhibiting APN with pIC50 value of 4.8, comparable to the reference standard. Further evaluation of derivative 8 against VEGFR2 and MMP9 as biomarkers for angiogenesis and invasion showed that the selected compound had an inhibitory activity on both proteins with pIC50 values of 6.7 and 6.4, respectively. Additionally, the migration ability of cells following treatment with the diphenylpyrazole derivative decreased to record a percentage wound closure of 57.77 for compound 8versus 97.03 for the control. The promising derivative arrested cell growth at the G1 phase inducing early and late apoptosis. Finally, docking and ADMET in silico studies were performed. New naturally based pyrazoline derivatives were investigated as anti-breast cancer agents targeting APN, VEGFR2 and MMP9. The effects on wound healing, cell cycle and apoptosis were evaluated. Docking and ADMET studies were performed as well.
引用
收藏
页码:22434 / 22448
页数:15
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