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dc.contributor.author
Ribone, Sergio Roman  
dc.contributor.author
Schenfeld, Esteban Martin  
dc.contributor.author
Madrid, Marcela  
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Pierini, Adriana Beatriz  
dc.contributor.author
Quevedo, Mario Alfredo  
dc.date.available
2018-10-23T19:25:59Z  
dc.date.issued
2016-01  
dc.identifier.citation
Ribone, Sergio Roman; Schenfeld, Esteban Martin; Madrid, Marcela; Pierini, Adriana Beatriz; Quevedo, Mario Alfredo; Evaluation and synthesis of AZT prodrugs with optimized chemical stabilities: Experimental and theoretical analyses; Royal Society of Chemistry; New Journal of Chemistry; 40; 3; 1-2016; 2383-2392  
dc.identifier.issn
1144-0546  
dc.identifier.uri
http://hdl.handle.net/11336/62948  
dc.description.abstract
The design of prodrugs of nucleoside reverse transcriptase inhibitors (NRTIs) constitutes a promising strategy to overcome several suboptimal pharmacotherapeutic properties of these kinds of drugs, among which zidovudine (AZT) is the most studied example. The chemical stability of prodrugs is a critical issue in the context of their pharmacotherapeutic performance since it constitutes a key event in the reconversion of the bioactive NRTIs. In this study, five prodrugs of AZT and lamivudine (3TC) were studied by means of DFT and classical molecular dynamics (MD) strategies in order to model the reaction coordinates involved in their chemical hydrolysis, and extend these conclusions to further structure rationalization of prodrugs. Therefore, the inclusion of explicit water molecules was found to be of great relevance to the mentioned reaction coordinates since it allowed a very good correlation between calculated reaction energy values and the corresponding hydrolysis constants. Based on these findings, three ester based prodrugs of AZT were designed, synthesized and evaluated regarding their chemical stability. These prodrugs exhibited optimized chemical stabilities when compared to the previously reported AZT prodrugs, which may result in an enhanced pharmacotherapeutic performance. In conclusion, the developed theoretical model provides a valuable assistance in the design and development of novel prodrugs of NTRIs with rationalized chemical stabilities.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Royal Society of Chemistry  
dc.rights
info:eu-repo/semantics/restrictedAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Prodrugs  
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Quantum Calculations  
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Chemical Stability  
dc.subject.classification
Otras Ciencias Químicas  
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Ciencias Químicas  
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CIENCIAS NATURALES Y EXACTAS  
dc.title
Evaluation and synthesis of AZT prodrugs with optimized chemical stabilities: Experimental and theoretical analyses  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2018-10-23T13:44:38Z  
dc.journal.volume
40  
dc.journal.number
3  
dc.journal.pagination
2383-2392  
dc.journal.pais
Reino Unido  
dc.description.fil
Fil: Ribone, Sergio Roman. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina  
dc.description.fil
Fil: Schenfeld, Esteban Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina  
dc.description.fil
Fil: Madrid, Marcela. Pittsburgh Supercomputing Center; Estados Unidos  
dc.description.fil
Fil: Pierini, Adriana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina  
dc.description.fil
Fil: Quevedo, Mario Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina  
dc.journal.title
New Journal of Chemistry  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1039/c5nj03002a  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://pubs.rsc.org/en/Content/ArticleLanding/2016/NJ/C5NJ03002A