分子模拟背景简介

分子对接技术的应用情况

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Contents

分子模拟背景简介

医学

物理

生命科学

材料学

分子模拟分子模拟 化学

分子模拟背景简介

分子对接技术应用情况

分子对接就是从已知结构的受体（靶蛋白或活性位点）和配体出发，通过化学计量学方法模拟分子的几何结构和分子间作用力来进行分子间相互作用识别并预测受体 - 配体复合物结构的方法。

目前，分子对接技术主要在药物研究领域发挥了重要作用。例如，研究小分子探针与细胞内生物大分子的相互作用，寻找小分子在生物体内的作用靶点，为新药开发寻找突破口；以结构生物学为基础，对正常生理过程中及与肝癌、肝炎等疾病相关的重要蛋白质的结构和功能进行系统的研究与分析，得到蛋白质药靶的三维结构，进行药物与靶标蛋白相互作用的动力学模拟研究。

早期的药物设计偏重于提高小分子活性的设计，并取得了一定的成果。因此，发展、利用各种分子对接方法进行新药的发现将成为一个研究热点。

文献

From: Bioorganic & Medicinal Chemistry

Authors: Qing-Zhong Zheng, Fei Zhang, Kui Cheng, YingYang, YuChen,

YongQian, Hong-Juan Zhang, Huan-Qiu Li, Chang-Fang Zhou, Shu-Qing An *,

Qing-Cai Jiao *, Hai-Liang Zhu *

IIII

IIIIIIII

IIIIIIIIIIII

IVIVIVIV

Introduction

Experiment

Results and discussion

Conclusion

Contents

文献

文献 -Introduction

Breast cancerBreast cancer

Ovarian cancerOvarian cancer

Lung cancerLung cancer

Prostate cancerProstate cancer

Receptor protein tyrosine kinasesReceptor protein tyrosine kinases

EGFREGFR

HER-2HER-2

文献 -Introduction

Nitrogen mustards are widely used in the treatment of a variety of cancer. But because of the high reactivity of nitrogen mustards, they are chemically unstable and produce many unwanted side effects including bone marrow toxicity and genotoxicity.

However, benzoic nitrogen mustard possessing relatively low toxicity is one of the earliest antitumor drugs in antibody-directed enzyme prodrug therapy. It is reported that benzoic nitrogen mustard derivatives possess favorable anticancer activity.

The synthesis

Biological

evaluation

Docking stimulation

文献 -Experiment

General procedure for the preparation of target compounds 5a–t

General procedure for the preparation of target compounds 5a–t

Cell proliferation assayCell proliferation assay

Preparation, purification of HER-2 and EGFR and inhibitory assay

Preparation, purification of HER-2 and EGFR and inhibitory assay

Molecular docking modelingMolecular docking modeling

ExperimentExperiment ELISA assay

MTT assay

文献 -Result and discussion

文献 -Result and discussion

文献 -Result and discussion

A series of new amide-coupled benzoic nitrogen mustard derivatives were synthesized, some of which displayed potent EGFR and HER-2 inhibitory.

Of all the studied compounds, compounds 5b and 5t exhibited the most potent inhibitory activity (as for 5b, IC50= 0.08μM for EGFR and IC50= 0.41μM for HER-2; as for 5t, IC50= 0.09μM for EGFR and IC50= 0.35μM for HER-2).

Docking simulation was performed to position compounds 5b and 5t into the EGFR active site to determine the probable binding model.

Antiproliferative assay results indicated that some of the benzoic nitrogen mustard derivatives possessed high antiproliferative activity against MCF-7. In particular, compounds 5b and 5t with potent inhibitory activity in tumor growth inhibition would be potential antitumor agents.

A series of new amide-coupled benzoic nitrogen mustard derivatives were synthesized, some of which displayed potent EGFR and HER-2 inhibitory.

Of all the studied compounds, compounds 5b and 5t exhibited the most potent inhibitory activity (as for 5b, IC50= 0.08μM for EGFR and IC50= 0.41μM for HER-2; as for 5t, IC50= 0.09μM for EGFR and IC50= 0.35μM for HER-2).

Docking simulation was performed to position compounds 5b and 5t into the EGFR active site to determine the probable binding model.

Antiproliferative assay results indicated that some of the benzoic nitrogen mustard derivatives possessed high antiproliferative activity against MCF-7. In particular, compounds 5b and 5t with potent inhibitory activity in tumor growth inhibition would be potential antitumor agents.

Conclusion

文献 -Conclusion

文献 -Reference

1. Yarden, Y.; Sliwkowski, M. X. Mol. Cell Biol. 2001, 2, 127.2. Hynes, N. E.; Stern, D. F. Biochim. Biophys. Acta 1994, 1198, 165.3. Slamon, D. J.; Clark, G. M.; Wong, S. G.; Levin, W. J.; Ullrich, A.; McGuire, W. L.Science 1987, 235, 177.4. Slamon, D. J.; Godolphin, W.; Jones, L. A. Science (Wash. DC) 1989, 244, 7075. Scheurle, D.; Jahanzeb, M.; Aronsohn, R. S.; Watzek, L.; Narayanan, R. H. Anticancer Res. 2000, 20, 2091.6. Cox, G.; Vyberg, M.; Melgaard, B.; Askaa, J.; Oster, A.; O’Byrne, K. J. Int. J. Cancer 2001, 92, 480.7. Gullick, W. J. Br. Med. Bull. 1991, 47, 87.8. Moscatello, D. K.; Holgado-Mudruga, M.; Godwin, A. K.; Ramirez, G.; Gunn, G.; Zoltick, P. W.; Biegel, J. A.; Hayes, R. L.; Wong, A. J. Cancer Res. 1995, 55, 5536.9. Wikstrand, C. J.; McLendon, R. E.; Friedman, A.; Bigner, D. D. Cancer Res. 1997, 57, 4130.

文献 -Reference

10. Bridges, A. J. Curr. Med. Chem. 1999, 6, 825.11. Boschelli, D. H. Drugs Future 1999, 24, 515.12. Denny, W. A. Curr. Med. Chem. 2001, 8, 533.13. Alexanian, R.; Dimopoulos, M. A. N. Eng. J. Med. 1994, 330, 484.14. Hansson, J.; Lewensohn, R.; Ringborg, U.; Nilsson, B. Cancer Res. 1987, 47, 2631.15. Rodney, M.; Carney, J. P.; Kelley, M. R.; Glassner, B. J.; Williams, D. A.; Samson,L. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 206.16. Brendal, M.; Ruhland, A. Mutat. Res. 1984, 133, 51.17. Zakaria, R.; Fouad, B.; Qiyu, Q.; Christopher, W.; Janet, M. H.; John, A. H.;Bertrand, J. J. C. J. Med. Chem. 2007, 50, 2605.18. Springer, C. J.; Antoniw, P.; Bagshawe, K. D.; Searle, F.; Bisset, G. M.; Jarman, M.J. Med. Chem. 1990, 33, 677.19. Niculescu-Duvaz, I.; Scanlon, I.; Niculescu-Duvaz, D.; Friedlos, F.; Martin, J.;Marais, R.; Springer, C. J. J. Med. Chem. 2004, 47, 2651.20. Taylor, C. K.; Abel, P. W.; Hulce, M.; Smith, D. D. Chem. Biol. Drug Des. 2007, 70, 216.

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