Next Article in Journal
A New 9,10-Dihydrophenanthrene and Cell Proliferative 3,4-δ-Dehydrotocopherols from Stemona tuberosa
Previous Article in Journal
Carboxylated Acyclonucleosides: Synthesis and RNase A Inhibition
Article Menu

Export Article

Open AccessArticle
Molecules 2015, 20(4), 5942-5964; doi:10.3390/molecules20045942

Probing the Relationship between Anti-Pneumocystis carinii Activity and DNA Binding of Bisamidines by Molecular Dynamics Simulations

Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, Warsaw 02 097, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Rino Ragno
Received: 3 March 2015 / Revised: 26 March 2015 / Accepted: 30 March 2015 / Published: 3 April 2015
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [3394 KB, uploaded 3 April 2015]   |  

Abstract

The anti-Pneumocystis carinii activity of 13 synthetic pentamidine analogs was analyzed. The experimental differences in melting points of DNA dodecamer 5'-(CGCGAATTCGCG)2-3' complexes (ΔTm), and in the biological activity measured using ATP bioluminescence assay (IC50) together with the theoretical free energy of DNA-ligand binding estimated by the proposed computational protocol, showed that the experimental activity of the tested pentamidines appeared to be due to the binding to the DNA minor groove with extended AT sequences. The effect of heteroatoms in the aliphatic linker, and the sulfonamide or methoxy substituents on the compound inducing changes in the interactions with the DNA minor groove was examined and was correlated with biological activity. In computational analysis, the explicit solvent approximation with the discrete water molecules was taken into account, and the role of water molecules in the DNA-ligand complexes was defined. View Full-Text
Keywords: water mediated DNA interaction; molecular docking; pentamidine analogs; anti-Pneumocystis carinii activity; DNA melting temperature water mediated DNA interaction; molecular docking; pentamidine analogs; anti-Pneumocystis carinii activity; DNA melting temperature
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).

Supplementary material

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

Żołek, T.; Maciejewska, D.; Żabiński, J.; Kaźmierczak, P.; Rezler, M. Probing the Relationship between Anti-Pneumocystis carinii Activity and DNA Binding of Bisamidines by Molecular Dynamics Simulations. Molecules 2015, 20, 5942-5964.

Show more citation formats Show less citations formats

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