Exploring three-dimensional quantitative structural activity relationship (3D-QSAR) analysis of SCH 66336 (Sarasar) analogues of farnesyltransferase inhibitors

Equbal, Tabish; Silakari, Om; Ravikumar, Muttineni

doi:10.1016/j.ejmech.2007.02.013

Cited by 19 publications

(12 citation statements)

References 16 publications

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“…The presence of two electrostatic descriptors around R 1 group of 1,2,4-triazole ring namely H þ /556 and H þ /837 with low positive coefficient in the final QSAR model-2, describes moderate electrostatic parameters required at this position. Besides, another two electrostatic descriptors of H þ /917 with negative coefficient and H þ /728 with positive coefficient indicate that a subtle balance of electrostatic interaction needed at the opposite area of R 1 group around 1,2,4-triazole ring [35].…”

Section: Full Papersmentioning

confidence: 99%

“…MFA attempts to postulate and represent the essential features of a receptor site from the aligned common features of the molecules that bind to it [33,34]. This approach can effectively evaluate the interaction energy between a probe and the set of aligned molecules at a series of points defined by a rectangular grid, especially for the analysis of datasets with available activity data but unknown receptor site structure [35]. The interaction energy values measured for each point of a 3D-grid were computed using atomic coordinates of binding molecules and can be used in the subsequent QSAR study.…”

Section: D-qsar Analysismentioning

confidence: 99%

See 1 more Smart Citation

Quantitative Structure–Activity Relationship Analysis of Some Thiourea Derivatives with Activities Against HIV‐1 (IIIB)

Chen

Xie

et al. 2009

QSAR Comb. Sci.

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Two-dimensional (2D) and Three-dimensional (3D) Quantitative Structure -Activity Relationship (QSAR) studies have been carried out on a series of 42 recently synthesized thiourea derivatives to find out the structural requirements of their protection of MT-4 cells against Human Immunodeficiency Virus (HIV)-1 (IIIB). The statistically significant 2D-QSAR model (r 2 ¼ 0.897) was developed by Genetic Function Approximation (GFA) when the number of descriptors in equation was set to four, indicating descriptors of S_aaCH, Shadow_XYfrac, Lowest Unoccupied Molecular Orbital (LUMO), and Hydrogen-Bond Acceptors (Hbond Acceptor) mainly control the bioactivity. The validation of the model was done by the full cross-validation tests, randomization tests, and external test set prediction. Molecular Field Analysis (MFA) investigated the substitutional requirements for the favorable receptor -drug interaction and constructed the best 3D-QSAR model using Genetic Partial Least Squares (G/PLS) method, showing that the electrostatic fields contribute significantly toward bioactivity. The results obtained by combining both methodologies give insight into the key features for designing more potent analogs against HIV-1(IIIB).

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Section: Full Papersmentioning

confidence: 99%

Section: D-qsar Analysismentioning

confidence: 99%

Quantitative Structure–Activity Relationship Analysis of Some Thiourea Derivatives with Activities Against HIV‐1 (IIIB)

Chen

Xie

et al. 2009

QSAR Comb. Sci.

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“…The maximum common subgroup (MCSG) method 31,32 was used to perform the alignment in this study. This method looks at molecules as points and lines, and uses the techniques of graph theory to identify patterns.…”

Section: D-qsar Analysismentioning

confidence: 99%

“…29,30 This approach can effectively evaluate the interaction energy between a probe and the set of aligned molecules at a series of points defined by a rectangular grid, especially for the analysis of data sets with available activity data but unknown receptor site structure. 31 The interaction energy values measured for each point of a 3D-grid were computed using atomic coordinates of binding molecules and could be used as the input for subsequent QSAR study.…”

Section: D-qsar Analysismentioning

confidence: 99%

Cluster Analysis and QSAR Study of Some Anti‐hepatitis B Virus Agents Comprising 4‐Aryl‐6‐chloro‐quinolin‐2‐ones and 5‐Aryl‐7‐chloro‐1,4‐benzodiazepines

Chen

Xie

et al. 2009

Chin. J. Chem.

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Chronic hepatitis B virus (HBV) infection has caused a global health crisis by infecting more than 400 million people, constituting the ninth leading cause of death in the world. There is an urgent demand for antiviral agents to effectively inhibit HBV infection based on the development of drug resistance and increasing infected numbers. Quantitative structure-activity relationship (QSAR) models were developed for a series of potent anti-hepatitis B virus agents comprising 4-aryl-6-chloro-quinolin-2-ones and 5-aryl-7-chloro-1,4-benzodiazepines using Cerius r ＝0.989) constructed by the genetic function approximation (GFA) methodology indicates that the activity was mainly governed by E-State-keys (S_sssN and S_sCl), electronic descriptor (LUMO), thermodynamic descriptor (Foct) and conformational descriptor (Energy). 3D-QSAR models were developed based on steric and electrostatic interactions by molecular field analysis (MFA) to investigate the substitutional requirements for the favorable receptor-drug interaction, showing that electrostatic interactions is crucial for the activity. The models derived can provide a preliminary valuable guidance for continuing search for novel potent anti-hepatitis B virus agents prior to synthesis.

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“…6 Recently developed representative FPTase inhibitors are FTI276, 7 L744,382, 8 as peptidomimetics of CaaX box, clavaric acid, 9 chaetomellic acid A, B 10 which is derived from microorganism, and arteminolide 11 from plants. In addition to these, there are some other FPTase inhibitors which is under clinical experiments, such as R-115777 (IC50 = 0.9 nM), 12 SCH-66336 (IC50 = 2 nM) 13 and BMS-214662 (IC50 = 0.7 nM).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Ligand Based 3D-QSAR of 2,3-Bis-benzylidenesuccinaldehyde Derivatives as New Class Potent FPTase Inhibitor, and Prediction of Active Molecules

Soung¹,

Kim²,

Kwon³

et al. 2010

Bulletin of the Korean Chemical Society

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In order to search new inhibitors against farnesyl protein transferase (FPTase), a series of 2,3-bis-benzylidenesuccinaldehyde derivatives (1-29) were synthesized and their inhibition activities (pI50) against FPTase were measured. From based on the reported results that the inhibitory activities of dimers 2,3-bis-benzylidenesuccinaldehydes were higher than those of monomers cinnamaldehydes, 3D-QSARs on FPTase inhibitory activities of the dimers (1-29) were studied quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis ( The dependence of CoMFA models on chance correlations was evaluated with progressive scrambling analyses. And the inhibitory activity exhibited a strong correlation with steric factors of the substrate molecules. Therefore, from the results of graphical analyses on the contour maps and of predicted higher inhibitory active compounds, it is suggested that the structural distinctions and descriptors that contribute to inhibitory activities (pI50) against FPTase will be able to applied new inhibitor design.

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Exploring three-dimensional quantitative structural activity relationship (3D-QSAR) analysis of SCH 66336 (Sarasar) analogues of farnesyltransferase inhibitors

Cited by 19 publications

References 16 publications

Quantitative Structure–Activity Relationship Analysis of Some Thiourea Derivatives with Activities Against HIV‐1 (IIIB)

Quantitative Structure–Activity Relationship Analysis of Some Thiourea Derivatives with Activities Against HIV‐1 (IIIB)

Cluster Analysis and QSAR Study of Some Anti‐hepatitis B Virus Agents Comprising 4‐Aryl‐6‐chloro‐quinolin‐2‐ones and 5‐Aryl‐7‐chloro‐1,4‐benzodiazepines

Synthesis and Ligand Based 3D-QSAR of 2,3-Bis-benzylidenesuccinaldehyde Derivatives as New Class Potent FPTase Inhibitor, and Prediction of Active Molecules

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