Abstract:
:Hologram quantitative structure-activity relationships (HQSAR) were applied to a data set of 41 cruzain inhibitors. The best HQSAR model (Q(2)=0.77; R(2)=0.90) employing Surflex-Sim, as training and test sets generator, was obtained using atoms, bonds, and connections as fragment distinctions and 4-7 as fragment size. This model was then used to predict the potencies of 12 test set compounds, giving satisfactory predictive R(2) value of 0.88. The contribution maps obtained from the best HQSAR model are in agreement with the biological activities of the study compounds. The Trypanosoma cruzi cruzain shares high similarity with the mammalian homolog cathepsin L. The selectivity toward cruzain was checked by a database of 123 compounds, which corresponds to the 41 cruzain inhibitors used in the HQSAR model development plus 82 cathepsin L inhibitors. We screened these compounds by ROCS (Rapid Overlay of Chemical Structures), a Gaussian-shape volume overlap filter that can rapidly identify shapes that match the query molecule. Remarkably, ROCS was able to rank the first 37 hits as being only cruzain inhibitors. In addition, the area under the curve (AUC) obtained with ROCS was 0.96, indicating that the method was very efficient to distinguishing between cruzain and cathepsin L inhibitors.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Freitas RF,Oprea TI,Montanari CAdoi
10.1016/j.bmc.2007.10.048subject
Has Abstractpub_date
2008-01-15 00:00:00pages
838-53issue
2eissn
0968-0896issn
1464-3391pii
S0968-0896(07)00897-8journal_volume
16pub_type
杂志文章abstract::Derivatives of chlorogenic acid or its analogues were synthesized by coupling protected chlorogenic acid or its analogues with p-octyloxyaniline and selected amino acids. Most of the compounds exhibited significant potency against Cryptococcus neoformans and Candida species with low toxicity to brine shrimps. The 4,5-...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(99)00130-3
更新日期:1999-09-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/0968-0896(95)00015-9
更新日期:1995-02-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(01)00080-3
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journal_title:Bioorganic & medicinal chemistry
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doi:10.1016/j.bmc.2017.02.066
更新日期:2017-04-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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更新日期:2002-03-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章,评审
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journal_title:Bioorganic & medicinal chemistry
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doi:10.1016/j.bmc.2006.04.044
更新日期:2006-08-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(01)00196-1
更新日期:2001-11-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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doi:10.1016/s0968-0896(02)00599-0
更新日期:2003-04-03 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.12.019
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.09.009
更新日期:2006-12-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.03.007
更新日期:2008-05-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:1999-05-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2003.09.004
更新日期:2003-11-17 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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doi:10.1016/s0968-0896(97)00138-7
更新日期:1997-10-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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更新日期:1994-06-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.06.052
更新日期:2016-09-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.06.043
更新日期:2013-09-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.11.052
更新日期:2006-04-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.08.047
更新日期:2007-11-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/0968-0896(95)00048-l
更新日期:1995-06-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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更新日期:2016-05-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2003.10.039
更新日期:2004-01-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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更新日期:2014-11-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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更新日期:2015-12-01 00:00:00