QSAR analysis of diaryl COX-2 inhibitors: Comparison of feature selection and train-test data selection methods

Soltani, Somaieh; Abolhasani, Hoda; Zarghi, Afshin; Jouyban, Abolghasem

doi:10.1016/j.ejmech.2010.02.055

Cited by 33 publications

(30 citation statements)

References 12 publications

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“…Combining of PLS with GA provides the possibility of descriptor selection from a pool of collinear descriptors without over fitting problem which could be happen using PLS method . The GAPLS toolbox that was developed by Leardi for QSAR studies was applied using the MATLAB software for descriptor selection based on the Soltani et al (2010) procedure.…”

Section: Gapls Methodsmentioning

confidence: 99%

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Developing 2D-QSAR models for naphthyridine derivatives against HIV-1 integrase activity

et al. 2014

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HIV-1 integrase is an extremely important nominee in developing new and effective drugs especially naphthyridine compounds against acquired immune deficiency syndrome. The quantitative structure-activity relationship (QSAR) modeling is the most powerful method in computer-aided drug design and will be used to help the design of new naphthyridine derivatives. Different computational 2D-QSAR procedures applied to predict the relationship between the computational descriptors of naphthyridine derivatives with their HIV-1 integrase inhibition activities. Four different models including stepwise-MLR, consensus stepwise-MLR, GAPLS-MLR, and consensus GAPLS-MLR with appropriate correlation between the calculated and experimental biological activities (pIC 50 ) against HIV-1 integrase were generated. Predictive QSAR models were obtained with R training 2 values of 0.848, 0.862, 0.709, and 0.751 as well as R test 2 values of 0.521, 0.651, 0.502, and 0.775 for stepwise-MLR, consensus stepwise-MLR, GAPLS-MLR, and consensus GAPLS-MLR models, respectively. QSAR models are high efficiency in prediction of the pIC 50 in comparison with other models because of concerning the combination of ''quantum and molecular mechanical'' descriptors. Combination of ''quantum'' and ''molecular mechanical'' descriptors improved our models with high efficient test set activity prediction potency. The obtained results provided useful information for understanding the effects of polarizability, electronegativity, and especially functional groups such as aromatic nitrogens that are important for the activities of naphthyridine compounds. The developed QSAR models will be efficient for the rational design of potent naphthyridine derivatives against HIV-1 integrase activity.

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Section: Gapls Methodsmentioning

confidence: 99%

“…We must have methods for detecting and assessing outliers in QSAR studies. There are different methods for outlier detection in which the scoring method is one of the most frequently applied methods (Soltani et al, 2010). The Y-outlier is employed in this study for detecting the different target variables.…”

Section: Recognition Of Outliermentioning

confidence: 99%

Developing 2D-QSAR models for naphthyridine derivatives against HIV-1 integrase activity

et al. 2014

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“…38,[55][56][57] Their success, to a great degree, is dependent on proper characterizations of the molecular structure and selection of the structural descriptors. A total of 1785 molecular descriptors, including functional group counts, 2D autocorrelations, information indices, GETAWAY descriptors, 3D-MoRSE descriptors, RDF descriptors, topological indices, WHIM descriptors, etc.…”

Section: Methodsmentioning

confidence: 99%

Relationship of Chemical Structure to <i>in Vitro</i> Anti-inflammatory Activity of Tirucallane Triterpenoids from the Stem Barks of <i>Aphanamixis grandifolia</i>

Guo

Wang

Zhang

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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A series of tirucallane triterpenoids isolated from the stem barks of Aphanamixis grandifolia were assessed for their anti-inflammatory activity, exhibiting from weak to strong anti-inflammatory activity, by testing their inhibitory effects on nitric oxide (NO) production and tumor necrosis factor-α (TNF-α) level in lipopolysaccharide (LPS) induced RAW264.7 murine macrophages. To explore the relationship between the structures and anti-inflammatory activity, a vast pool of molecular descriptors for each isolate were calculated. Genetic algorithms (GA) or simulated annealing (SA) based partial least squares (GA-PLS and SA-PLS) algorithms identified some important descriptor combinations, which were correlated with both sets of the anti-inflammatory data by partial least squares 2 (PLS2) method. S-Plot was used to visualize the descriptor influence in the PLS2 model, disclosed five most important molecular descriptors, nOHt, RDF150m, lip_vio-lation, Mor32m and JhetZ.Key words Aphanamixis grandifolia; tirucallane triterpenoid; anti-inflammatory activity; nitric oxide; tumor necrosis factor-α; structure-activity relationship Inflammation is a normal and crucial response of the organism to various stimuli including physical damage, ultra violet irradiation, microbial invasion and immune reactions, playing a pivotal role in host defense.1,2) While inflammatory cascades may cause pain, tissue damage, and a wide range of human acute and chronic inflammatory diseases, such as chronic asthma, rheumatoid arthritis and multiple sclerosis, and psoriasis.3) Many of these diseases with increasing incidence rate are particularly debilitating to the patient's functional capacity and quality of life.Macrophages have vital functions in maintaining body homeostasis, as well as in inflammatory processes, which are endowed with the ability to release a variety of mediators including the free radical nitric oxide (NO), 4) one of the most versatile regulator in the immune system. 5) Overproduction of NO can exacerbate inflammation, playing an important role in the pathogenesis of several chronic and systemic inflammation diseases, such as rheumatoid arthritis. 6,7)Tumor necrosis factor-α (TNF-α), one of the most important pro-inflammatory cytokines, is also massively produced by the activated macrophages and monocytes at local sites of inflammation.8) Its excessive production further triggers the secretion of other inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) and thereby aggravates the inflammation in many autoimmune/inflammatory diseases. 9-11)Exposure to major anti-inflammatory agents, such as corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), is known to increase substantially the risk of serious side effects.3,12) Therefore, there is an unmet medical need for new treatment strategies, which could be possibly filled by rational phytopharmaceuticals with a favorable benefit/risk ratio. Recent investigations into the anti-inflamm...

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“…The principal components (PCs) as a new set of variables (mutually orthogonal) were obtained by this method. The first PC contains the largest variance and the second PC contains the second largest variance [26]. The variable selection in PCA was performed using the Fisher's weights approach and the results are summarized as the following Eqs.…”

Section: Ache-qsarmentioning

confidence: 99%

Phosphorhydrazides as urease and acetylcholinesterase inhibitors: biological evaluation and QSAR study

2016

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step of organic nitrogen mineralization to produce ammonia and carbamate. The carbamate produced during this reaction spontaneously decomposes, at physiological pH, to give a second molecule of ammonia and bicarbonate [3][4][5][6]. The hydrolysis of the reaction products causes an abrupt overall pH increase, the major cause for the negative side effects of the action of urease both for human and animal health, and for agriculture. Urease inhibitors have also been proposed to control urea hydrolysis in soil [6][7][8][9][10][11][12][13][14][15][16]. In particular, compound with the P(X)-NH2 segment (X = O, S) have received considerable attention as urease inhibitors. The most effective inhibitors are substituted both thiophosphinicamide and phosphinicamide families. Many phosphoramide compounds are the most effective compounds currently available to retard the hydrolysis of urea fertilizer in soil and to decrease ammonia volatilization and nitrite accumulation in soils treated with urea. (Thio)phosphoramide inhibited urease by forming a chelated complex with the nickel ion in the active site of enzyme. Phosphoramide acts as urease inhibitors by coordinating itself to the nickel ions of active site [15]. The oxygen or sulfur atoms and amide group of the inhibitor molecule are engaged in the formation of a bridge between the Ni(1) and Ni(2) ions. In this work, we have compared the effectiveness of new (thio) phosphorhydrazide compounds (1-17) to inhibit jack bean urease toward (thio)phosphoramides. In addition, we carried out quantitative structure-activity relationship (QSAR) studies on the aforementioned derivatives to gain an understanding of the activity shown by such compounds, to propose its union mode to the urease active site, and to try to create the correlation between the electronic and structural parameters in contrast to the inhibition potency.Abstract New phosphorhydrazide compounds (1-7, 13, 15-16) and thiophosphorhydrazide (14 and 17) were synthesized and characterized by 31 P, 13 C, 1 H NMR and IR spectroscopy. Furthermore, the crystal structure of compound (C 6 H 5 NH)(C 6 H 5 O)P(O)(NH-NH 2 ) (2) was investigated. The activities of derivatives on acetylcholinesterase (AChE) and urease were determined. Quantitative structure-activity relationship (QSAR) was used to understand the relationship between molecular structural features and inhibitory. DFT-QSAR models for enzymes demonstrated the importance of E LUMO parameter in describing the antiAChE and anti-urease activities of the synthesized compounds. The correlation matrix of QSAR models and docking analysis confirmed that electrophilicity descriptor can control the influence of the polarizability properties of N-H functional group of PAH derivatives in the inhibition of enzymes.

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QSAR analysis of diaryl COX-2 inhibitors: Comparison of feature selection and train-test data selection methods

Cited by 33 publications

References 12 publications

Developing 2D-QSAR models for naphthyridine derivatives against HIV-1 integrase activity

Developing 2D-QSAR models for naphthyridine derivatives against HIV-1 integrase activity

Relationship of Chemical Structure to <i>in Vitro</i> Anti-inflammatory Activity of Tirucallane Triterpenoids from the Stem Barks of <i>Aphanamixis grandifolia</i>

Phosphorhydrazides as urease and acetylcholinesterase inhibitors: biological evaluation and QSAR study

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