| Simple but highly effective three-dimensional chemical-feature-based pharmacophore model for diketo acid derivatives as hepatitis C virus RNA-dependent RNA polymerase inhibitors. | |
| | |
MedLine Citation:
|
PMID: 16190757 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
A molecular modeling strategy using aryl diketo acid (ADK) derivatives recently reported in the literature as hepatitis C virus (HCV) polymerase inhibitors was designed. A 3D chemical-feature-based pharmacophore model was developed using Catalyst software, which produced 10 pharmacophore hypotheses. The top-ranked one (Hypo 1), characterized by a high correlation coefficient (r = 0.965), consisted of two hydrogen bond acceptors, one negative ionizable moiety, and two hydrophobic aromatics. This model was used to predict the anti-RNA-dependent RNA polymerase (anti-RdRp) activity of 6-(1-arylmethylpyrrol-2-yl)-1,4-dioxo-5-hexenoic acids and other ADK derivatives previously synthesized in our laboratories as HIV-1 integrase inhibitors. Furthermore, the experimental IC50 values of 9 compounds, tested in vitro against recombinant HCV polymerase, were compared with the corresponding values predicted using Hypo1. A good agreement between experimental and simulated data was obtained. The results demonstrate that the hypothesis derived in this study can be considered to be a useful tool in designing new leads based on ADK scaffolds as HCV RdRp inhibitors. |
| | |
Authors:
|
Roberto Di Santo; Maurizio Fermeglia; Marco Ferrone; Maria Silvia Paneni; Roberta Costi; Marino Artico; Alessandra Roux; Mirko Gabriele; Keith D Tardif; Aleem Siddiqui; Sabrina Pricl |
Related Documents
:
|
22165277 - Russia: district court upholds legal ban on opioid substitution treatment. 23324657 - Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography... 21938107 - Clinico-epidemiological profile of hiv/tb coinfected patients in vadodara, gujarat. 21956987 - Use of dried-blood-spot samples and in-house assays to identify antiretroviral drug res... 9512147 - Vitritis as the primary manifestation of ocular syphilis in patients with hiv infection. 23509897 - Formal hepatitis c education enhances hcv care coordination, expedites hcv treatment an... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Journal of medicinal chemistry Volume: 48 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 2005 Oct |
Date Detail:
|
Created Date: 2005-09-29 Completed Date: 2005-11-28 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 6304-14 Citation Subset: IM |
Affiliation:
|
Istituto Pasteur-Fondazione Cenci Bolognetti-Dipartimento di Studi Farmaceutici, University of Rome La Sapienza, P.le Aldo Moro 5, I-00185 Roma, Italy. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antiviral Agents
/
chemistry* Drug Design Enzyme Inhibitors / chemistry* Hepacivirus / enzymology* Keto Acids / chemistry* Models, Molecular Molecular Structure Quantitative Structure-Activity Relationship RNA Replicase / antagonists & inhibitors*, chemistry* |
| Chemical | |
Reg. No./Substance:
|
0/Antiviral Agents; 0/Enzyme Inhibitors; 0/Keto Acids; EC 2.7.7.48/RNA Replicase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: DrugScore(CSD)-knowledge-based scoring function derived from small molecule crystal data with superi...
Next Document: Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular model...