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Pentacycloundecane-...
Pentacycloundecane-diol-Based HIV-1 Protease Inhibitors : Biological Screening, 2D NMR, and Molecular Simulation Studies
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Honarparvar, Bahareh (author)
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Makatini, Maya M. (author)
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Pawar, Sachin A. (author)
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- Petzold, Katja (author)
- School of Chemistry, University of KwaZulu-Natal, Durban 4001 (South Africa)
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Soliman, Mahmoud E. S. (author)
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- Arvidsson, Per I. (author)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
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Sayed, Yasien (author)
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Govender, Thavendran (author)
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Maguire, Glenn E. M. (author)
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Kruger, Hendrik G. (author)
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(creator_code:org_t)
- 2012-04-27
- 2012
- English.
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In: ChemMedChem. - : Wiley. - 1860-7179 .- 1860-7187. ; 7:6, s. 1009-1019
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
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- Novel compounds incorporating a pentacycloundecane (PCU) diol moiety were designed, synthesized, and evaluated as inhibitors of the wild-type C-South African (C-SA) HIV-1 protease. Seven compounds are reported herein, three of which displayed IC50 values in the 0.50.6 mu M range. The cytotoxicity of PCU cage peptides toward human MT-4 cells appears to be several orders of magnitude less toxic than the current antiviral medications ritonavir and lopinavir. NMR studies based on the observed through-space 1H,1H distances/contacts in the EASY-ROESY spectra of three of the considered PCU peptide inhibitors enabled us to describe their secondary solution structure. Conserved hydrogen bonding interactions were observed between the hydroxy group of the PCU diol inhibitors and the catalytic triad (Asp25, Ile26, Gly27) of HIV protease in docking and molecular dynamics simulations. The biological significance and possible mode of inhibition by PCU-based HIV protease inhibitors discussed herein facilitates a deeper understanding of this family of inhibitors and their potential application to a vast number of alternative diseases related to proteases.
Subject headings
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
Keyword
- HIV-1 protease
- inhibitors
- molecular docking
- peptides
- transition-state analogues
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Honarparvar, Bah ...
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Makatini, Maya M ...
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Pawar, Sachin A.
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Petzold, Katja
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Soliman, Mahmoud ...
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Arvidsson, Per I ...
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show more...
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Sayed, Yasien
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Govender, Thaven ...
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Maguire, Glenn E ...
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Kruger, Hendrik ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Chemical Science ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medicinal Chemis ...
- Articles in the publication
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ChemMedChem
- By the university
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Uppsala University
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Umeå University