Study on CCR5 Receptor Antagonists as an Anti-Prostate Cancer: Inhibition Activity, QSAR and Molecular Docking

DOI

10.2991/iccst-15.2015.9How to use a DOI?

Keywords

CCR5, docking, maraviroc, prostate, QSAR

Abstract

Chemokine receptor CCR5, a G protein-coupled receptor (GPCR), has been shown as a viable target in drug discovery due to its involvement in HIV entry and cancer. In HIV pathogenesis, CCR5 acts as an essential co-receptor for HIV invasion into host cells; whereas in cancer, it provides a pro-inflammatory environment promoting cell invasion and proliferation in several cancers. Within those cancers, prostate cancer specimens have also been shown to over express CCR5. Thus, development of CCR5 antagonists may provide novel prostate cancer therapy. Several small molecule CCR5 antagonists have been developed as anti-prostate cancer such as anibamine and carboxymethyl-glucan (CM-G). In this paper, we designed a series of N-(5-(1-benzylpiperidin-4-yl)-2-hydroxyphenyl)formamide derivatives as anti-prostate cancer. The developed model was conducted based on molecular docking studies and validated by standard QSAR parameters. The QSAR analysis using a series of N-(5-(1-benzylpiperidin-4-yl)-2-hydroxyphenyl)formamide derivatives was successfully carried out to build a statistically significant model possessing a good correlative and predictive capability for the inhibition CCR5 antagonists. This analysis could be help in developing potential inhibition candidates for an anti-prostate cancer. Docking simulation was performed by AutoDock 4.1.5.6. The results showed that the main parameters of QSAR equation for inhibition CCR5 activity were AM1_dipole, AM1_HOMO, ASA_H, AM1_E and mr with r2, q2 and F of 0.865; 0.997216 and 4.233015, respectively. The docking results revealed that N-(5-(1-benzylpiperidin-4-yl)-2-hydroxyphenyl) formamide and its derivative can interact to binding sites of the studied CCR5 receptor formed hydrogen bond with Tyr37, Trp86, Tyr108, Phr182, Gln194, Ile198, Tyr251, Glu283, and Met287. They have the same pattern of hydrogen bonds with the known binding ligands maraviroc (PDB ID 4MBS) for CCR5.

Copyright

© 2015, the Authors. Published by Atlantis Press.

Open Access

This is an open access article distributed under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

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TY  - CONF
AU  - Nursamsiar
AU  - Lina Nurfadhila
AU  - Iman S. Pratama
AU  - Aiyi Asnawi
AU  - Slamet I. Surantaatmadja
PY  - 2015/01
DA  - 2015/01
TI  - Study on CCR5 Receptor Antagonists as an Anti-Prostate Cancer: Inhibition Activity, QSAR and Molecular Docking
BT  - Proceedings of the 3rd International Conference on Computation for Science and Technology
PB  - Atlantis Press
SP  - 40
EP  - 44
SN  - 2352-538X
UR  - https://doi.org/10.2991/iccst-15.2015.9
DO  - 10.2991/iccst-15.2015.9
ID  - 2015/01
ER  -