Design, Synthesis, and Biological Evaluation of Pyrazoline-Based Hydroxamic Acid Derivatives as Aminopeptidase N (APN) Inhibitors

ChemMedChem ◽  
2018 ◽  
Vol 13 (5) ◽  
pp. 431-436 ◽  
Author(s):  
Jiangying Cao ◽  
Jie Zang ◽  
Chunhua Ma ◽  
Xiaoguang Li ◽  
Jinning Hou ◽  
...  
Keyword(s):  
Hydroxamic Acid ◽  
Biological Evaluation ◽  
Aminopeptidase N ◽  
Design Synthesis ◽  
Synthesis And Biological Evaluation ◽  
Hydroxamic Acid Derivatives

Synthesis and 4D-QSAR Studies of Alanine Hydroxamic Acid Derivatives as Aminopeptidase N Inhibitors

2019 ◽  
Vol 16 ◽  
Author(s):  
Min Gao ◽  
Qiao Li Lv ◽  
Hou Pan Zhang ◽  
Guo Gang Tu
Keyword(s):  
Biological Activity ◽  
Active Site ◽  
Hydroxamic Acid ◽  
Binding Mode ◽  
Qsar Model ◽  
Aminopeptidase N ◽  
Design Synthesis ◽  
Qsar Studies ◽  
Hydroxamic Acid Derivatives

Background: As a target for anticancer treatment, aminopeptidase N (APN) shows its overexpression on diverse malignant tumor cells and associates with cancer invasion, angiogenesis and metastasis. Objective: Design, synthesis and biological activity evaluation of alanine hydroxamic acid derivatives as APN inhibitors, and investigation the binding mode of inhibitors in the APN active site. Methods: Alanine hydroxamic acid derivatives were synthesized and evaluated for their in vitro anti-cancer activity using CCK-8 assay. Molecular docking and 4D-QSAR studies were carried out to suggest the mechanism of biological activity. Results: Compared with Bestatin, compound 9b showed the best APN inhibition activity. The putative binding mode of 9b in the APN active site was also discussed. Moreover, the robust and reliable 4D-QSAR model exhibited the following statistics: R2 = 0.9352, q2LOO = 0.8484, q2LNO =0.7920, R2Pred = 0.8739. Conclusion: Newly synthesized compounds exerted acceptable anticancer activity and further investigation on current scaffold would be beneficial.

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