Literature DB >> 27904990

Computer modeling in predicting the bioactivity of human 5-lipoxygenase inhibitors.

Mengdi Zhang1, Zhonghua Xia1, Aixia Yan2,3.   

Abstract

5-Lipoxygenase (5-LOX) is a key enzyme in the inflammatory path. Inhibitors of 5-LOX are useful for the treatment of diseases like arthritis, cancer, and asthma. We have collected a dataset including 220 human 5-LOX inhibitors for classification. A self-organizing map (SOM), a support vector machine (SVM), and a multilayer perceptron (MLP) algorithm were used to build models with selected descriptors for classifying 5-LOX inhibitors into active and weakly active ones. MACCS fingerprints were used in this model building process. The accuracy (Q) and Matthews correlation coefficient (MCC) of the best SOM model (Model 1A) were 86.49% and 0.73 on the test set, respectively. The Q and MCC of the best SVM model (Model 2A) were 82.67% and 0.64 on the test set, respectively. The Q and MCC of the best MLP model (Model 3B) were 84.00% and 0.67 on the test set, respectively. In addition, 180 inhibitors with bioactivities measured by fluorescence method were further used for a quantitative prediction. Multiple linear regression (MLR) and SVM algorithms were used to build models to predict the [Formula: see text] values. The correlation coefficients (R) of the MLR model (Model Q1) and the SVM model (Model Q2) were 0.72 and 0.74 on the test set, respectively.

Entities:  

Keywords:  Human 5-lipoxygenase (5-LOX) inhibitors; Multilayer perceptron network (MLP); Self-organizing map (SOM); Structure–activity relationship (SAR); Support vector machine (SVM)

Mesh:

Substances:

Year:  2016        PMID: 27904990     DOI: 10.1007/s11030-016-9709-4

Source DB:  PubMed          Journal:  Mol Divers        ISSN: 1381-1991            Impact factor:   2.943


  47 in total

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2.  Development of 3,5-dinitrobenzoate-based 5-lipoxygenase inhibitors.

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4.  In vitro 12(S)-HETE and leukotriene metabolism inhibitory activity of sesquiterpenes of Warburgia ugandensis.

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Journal:  Planta Med       Date:  2006-05-29       Impact factor: 3.352

5.  N-1, C-3 substituted indoles as 5-LOX inhibitors--in vitro enzyme immunoaasay, mass spectral and molecular docking investigations.

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Journal:  Bioorg Med Chem Lett       Date:  2013-01-03       Impact factor: 2.823

6.  Identification of 1, 4-Dihydrothieno [3', 2':5, 6]thiopyrano[4, 3-c] pyrazole derivatives as human 5-Lipo-oxygenase inhibitors.

Authors:  Jianshu Hu; Wei Zhu; Hu Meng; Ying Liu; Xin Wang; Chun Hu
Journal:  Chem Biol Drug Des       Date:  2014-06-21       Impact factor: 2.817

7.  Ascorbic acid 6-palmitate: a potent inhibitor of human and soybean lipoxygenase-dependent lipid peroxidation.

Authors:  Riyaz Mohamed; Shaista Tarannum; Manjunath Yariswamy; Hamse K Vivek; Jalahalli M Siddesha; Nataraju Angaswamy; Bannikuppe S Vishwanath
Journal:  J Pharm Pharmacol       Date:  2013-12-22       Impact factor: 3.765

8.  Pharmacology of PF-4191834, a novel, selective non-redox 5-lipoxygenase inhibitor effective in inflammation and pain.

Authors:  Jaime L Masferrer; Ben S Zweifel; Medora Hardy; Gary D Anderson; Dawn Dufield; Luz Cortes-Burgos; Robert A Pufahl; Matthew Graneto
Journal:  J Pharmacol Exp Ther       Date:  2010-04-08       Impact factor: 4.030

9.  Bioactivity-guided fractionation of the lipoxygenase and cyclooxygenase inhibiting constituents from Chisocheton polyandrus Merr.

Authors:  Kit Yee Chan; Khalit Mohamad; Audrey J A Ooi; Zamrie Imiyabir; Lip Yong Chung
Journal:  Fitoterapia       Date:  2012-04-28       Impact factor: 2.882

10.  Discovery of a novel dual fungal CYP51/human 5-lipoxygenase inhibitor: implications for anti-fungal therapy.

Authors:  Eric K Hoobler; Ganesha Rai; Andrew G S Warrilow; Steven C Perry; Christopher J Smyrniotis; Ajit Jadhav; Anton Simeonov; Josie E Parker; Diane E Kelly; David J Maloney; S L Kelly; Theodore R Holman
Journal:  PLoS One       Date:  2013-06-24       Impact factor: 3.240

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