Hybrid 2D/3D-quantitative structure-activity relationship and modeling studies perspectives of pepstatin A analogs as cathepsin D inhibitors

被引：7

作者：

Arodola, Olayide A. ^{[1
]}

Soliman, Mahmoud E. S. ^{[1
]}

机构：

[1] Univ KwaZulu Natal, Dept Pharmaceut Chem, ZA-4000 Durban, Kwazulu Natal, South Africa

来源：

FUTURE MEDICINAL CHEMISTRY | 2018年 / 10卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

2D-QSAR; 3D-QSAR; accelerated molecular dynamics; ADME profiling; cathepsin D; conventional molecular dynamics; docking study; HIV/cancer co-infection; hybrid QM/MM; QSAR validation; MOLECULAR-DYNAMICS SIMULATIONS; BREAST-CANCER CELLS; AIDS-RELATED MALIGNANCIES; CYCLIC TERTIARY-AMINES; PROCATHEPSIN-D; KAPOSIS-SARCOMA; FORCE-FIELD; ACTIVATION PEPTIDE; HOMOSEXUAL-MEN; CRYSTAL-STRUCTURES;

D O I：

10.4155/fmc-2017-0077

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Aim: Cathepsin D, one of the attractive targets in the treatment of breast cancer, has been implicated in HIV neuropathogenesis with potential proteolytic effects on chemokines. Methodology/result: Diverse modeling tools were used to reveal the key structural features affecting the inhibitory activities of 78 pepstatin A analogs. Analyses were performed to investigate the stability, rationality and fluctuation of the analogs. Results showed a clear correlation between the experimental and predicted activities of the analogs as well as the variation in their activities relative to structural modifications. Conclusion: The insight gained from this study offers theoretical references for understanding the mechanism of action of cathepsin D and will aid in the design of more potent and clinically-relevant drugs.

引用

页码：5 / 26

页数：22

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