Novel aromatic inhibitors of influenza virus neuraminidase make selective interactions with conserved residues and water molecules in the active site 1 1Edited by I. A. Wilson

Finley, James B.; Atigadda, Venkatram R.; Duarte, Franco; Zhao, James J; Brouillette, Wayne J.; Air, Gillian M.; Luo, Ming

doi:10.1006/jmbi.1999.3180

Cited by 57 publications

(44 citation statements)

References 30 publications

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“…Indeed, most of the reported water-mediated interactions seem to be formed to stabilize the protein-ligand complex by establishing bridges to the protein site. [5][6][7] However, usually no conclusions can be drawn about the real benefit of these water interactions as the studies lack the comparison with the corresponding water-free reference states. Moreover, it is generally believed that the displacement of the bound water molecules leads to an improved binding affinity, 8 but on the other hand, impressive cases where no gain in binding affinity could be observed upon water displacement have been reported.…”

Section: Introductionmentioning

confidence: 98%

Impact of Ligand and Protein Desolvation on Ligand Binding to the S1 Pocket of Thrombin

Biela

Khayat

Tan

et al. 2012

Journal of Molecular Biology

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Section: Introductionmentioning

confidence: 98%

Impact of Ligand and Protein Desolvation on Ligand Binding to the S1 Pocket of Thrombin

Biela

Khayat

Tan

et al. 2012

Journal of Molecular Biology

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“…However, the automated docking provides us a way to predict the postulated bioactive conformations of ligands, which can not only be used to build more reliable 3D QSAR models, but also eliminate the difficulty in aligning compounds that covers more than one structure types. To date, a number of crystal structures of NA-inhibitor complexes have been released, in which different kinds of NIs bound to the active site in a similar pattern [7,12,13,[46][47][48]. Investigation on these structures also showed that there is virtually no change in the orientation of the side chain amino acids of the NA active site, except for some minor conformational changes in Glu276 and Arg224.…”

Section: Molecular Modelingmentioning

confidence: 95%

QSAR analyses on avian influenza virus neuraminidase inhibitors using CoMFA, CoMSIA, and HQSAR

Zheng

Liu

et al. 2006

J Comput Aided Mol Des

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The recent wide spreading of the H5N1 avian influenza virus (AIV) in Asia, Europe and Africa and its ability to cause fatal infections in human has raised serious concerns about a pending global flu pandemic. Neuraminidase (NA) inhibitors are currently the only option for treatment or prophylaxis in humans infected with this strain. However, drugs currently on the market often meet with rapidly emerging resistant mutants and only have limited application as inadequate supply of synthetic material. To dig out helpful information for designing potent inhibitors with novel structures against the NA, we used automated docking, CoMFA, CoMSIA, and HQSAR methods to investigate the quantitative structure-activity relationship for 126 NA inhibitors (NIs) with great structural diversities and wide range of bioactivities against influenza A virus. Based on the binding conformations discovered via molecular docking into the crystal structure of NA, CoMFA and CoMSIA models were successfully built with the cross-validated q (2) of 0.813 and 0.771, respectively. HQSAR was also carried out as a complementary study in that HQSAR technique does not require 3D information of these compounds and could provide a detailed molecular fragment contribution to the inhibitory activity. These models also show clearly how steric, electrostatic, hydrophobicity, and individual fragments affect the potency of NA inhibitors. In addition, CoMFA and CoMSIA field distributions are found to be in well agreement with the structural characteristics of the corresponding binding sites. Therefore, the final 3D-QSAR models and the information of the inhibitor-enzyme interaction should be useful in developing novel potent NA inhibitors.

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“…Accordingly, oseltamivir presents greater lipophilicity and, consequently, greater bioavailability (Fatima et al, 2005;Finley et al, 1999;Hayden et al, 1999;He et al, 1999).…”

Section: Antiviralsmentioning

confidence: 99%

Prodrugs available on the Brazilian pharmaceutical market and their corresponding bioactivation pathways

Parise-Filho

Polli

Barberato‐Filho

et al. 2010

Braz. J. Pharm. Sci.

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The aim of this paper was to emphasize the importance of prodrug design to therapy, by examining examples available on the Brazilian pharmaceutical market. The principles of prodrug design are briefly discussed herein. Examples of prodrugs from many important therapeutic classes are shown and their advantages relative to the drugs they are derived from are also discussed. Considering the importance of these therapeutic classes, from both therapy and economic standpoints, prodrug design is a very valuable aspect in the research of new drugs and for the pharmaceutical industry as a whole.Uniterms: Prodrug design. Molecular modification. Drug development.O objetivo do trabalho foi ressaltar a importância do planejamento de pró-fármacos para a terapia, por meio de exemplos disponíveis no mercado farmacêutico brasileiro. Os princípios da latenciação são sucintamente discutidos. Apresentam-se exemplos de pró-fármacos de muitas classes terapêuticas importantes e as vantagens relativas aos fármacos dos quais derivam são, também, discutidas. Considerando-se a importância dessas classes terapêuticas, tanto do aspecto terapêutico quanto do econômico, o planejamento de pró-fármacos representa aspecto de grande valor na busca de novos fármacos e na indústria farmacêutica como um todo.Uniterms: Pró-fármacos/planejamento Fármacos/latenciação. Modificação molecular. Fármacos/ desenvolvimento.

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Novel aromatic inhibitors of influenza virus neuraminidase make selective interactions with conserved residues and water molecules in the active site 1 1Edited by I. A. Wilson

Cited by 57 publications

References 30 publications

Impact of Ligand and Protein Desolvation on Ligand Binding to the S1 Pocket of Thrombin

Impact of Ligand and Protein Desolvation on Ligand Binding to the S1 Pocket of Thrombin

QSAR analyses on avian influenza virus neuraminidase inhibitors using CoMFA, CoMSIA, and HQSAR

Prodrugs available on the Brazilian pharmaceutical market and their corresponding bioactivation pathways

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