Next Article in Journal
Leptadenia reticulata (Retz.) Wight & Arn. (Jivanti): Botanical, Agronomical, Phytochemical, Pharmacological, and Biotechnological Aspects
Next Article in Special Issue
Newly Synthesized Doxorubicin Complexes with Selected Metals—Synthesis, Structure and Anti-Breast Cancer Activity
Previous Article in Journal
Mechanistic Explanation of the Weak Carbonic Anhydrase’s Esterase Activity
Previous Article in Special Issue
Synthesis and Antiproliferative Activity of Novel All-Trans-Retinoic Acid-Podophyllotoxin Conjugate towards Human Gastric Cancer Cells
Article Menu
Issue 6 (June) cover image

Export Article

Open AccessArticle
Molecules 2017, 22(6), 1020; doi:10.3390/molecules22061020

Determination of Structural Requirements of N-Substituted Tetrahydro-β-Carboline Imidazolium Salt Derivatives Using in Silico Approaches for Designing MEK-1 Inhibitors

School of Pharmacy, China Medical University, Liaoning 110122, China
These authors contributed equally to this work
*
Author to whom correspondence should be addressed.
Received: 9 May 2017 / Revised: 8 June 2017 / Accepted: 12 June 2017 / Published: 19 June 2017
View Full-Text   |   Download PDF [3608 KB, uploaded 20 June 2017]   |  

Abstract

Novel N-substituted tetrahydro-β-carboline imidazolium salt derivatives proved to have potent antitumor activity in past research. The Topomer CoMFA and CoMSIA function in Sybyl-X 2.0 software was applied for the identification of important features of N-substituted tetrahydro-β-carboline-imidazolium salt derivative moieties. In the case of Topomer CoMFA, all the compounds were split into two fragments which were used to generate a 3D invariant representation, the statistical results of the Topomer CoMFA model: q2 value of 0.700; r2 value of 0.954; with 5 optimum components. The database alignment was utilized for building the CoMSIA model, and the CoMSIA model had q2 and r2 values of 0.615 and 0.897, with 4 optimum components. Target fishing of the PharmMapper platform was utilised for finding potential targets, the human mitogen-activated protein kinase 1 (MEK-1) was found to be the primary potential target for the three compounds with the fit scores of 6.288, 5.741, and 6.721. The molecular docking technique of MOE 2015 was carried out to identify the interactions of amino acids surrounding the ligand, and correlating QASR contour maps were used to identify structural requirements of N-substituted tetrahydro-β-carboline imidazolium salt moieties. Molecular dynamics and simulation studies proved that the target protein was stable for 0.8–5 ns. The pivotal moieties of N-substituted tetrahydro-β-carboline imidazolium salt derivatives and its potential targets were verified by the QASR study, PharmMapper, and the molecular docking study which would be helpful to design novel MEK-1 inhibitors for anticancer drugs. View Full-Text
Keywords: 3D-QSAR; MEK-1; inhibitors; docking; molecular dynamics simulations 3D-QSAR; MEK-1; inhibitors; docking; molecular dynamics simulations
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Liang, J.; Wang, M.; Li, X.; He, X.; Cao, C.; Meng, F. Determination of Structural Requirements of N-Substituted Tetrahydro-β-Carboline Imidazolium Salt Derivatives Using in Silico Approaches for Designing MEK-1 Inhibitors. Molecules 2017, 22, 1020.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top