Exploration of physicochemical properties and molecular modelling studies of 2-sulfonyl-phenyl-3-phenyl-indole analogs as cyclooxygenase-2 inhibitors

Gupta, Arun Kumar; Gupta, Revathi A.; Soni, Love Kumar; Kaskhedikar, S. G.

doi:10.1016/j.ejmech.2007.06.022

Cited by 26 publications

(13 citation statements)

References 24 publications

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“…The sulfonamide moiety, which is important for COX-2 selectivity, interacts with the amino acid residues of a second enzyme pocket by forming hydrogen bonds between O-atoms of the SO 2 NH 2 substituent and Phe 518 . [46] Due to the lower COX-2 inhibition activity of 3d it seems that the carbaborane cluster exhibits different interactions with the hydrophobic cavity, which is possibly also due to the approximately 40% larger volume compared to a phenyl ring. Furthermore, the moderate COX-1 inhibition of compound 3d suggests a different binding mode in comparison to sulfonyl-containing 1,2-diphenyl indoles.…”

Section: Resultsmentioning

confidence: 99%

2‐Carbaborane‐3‐phenyl‐1H‐indoles—Synthesis via McMurry Reaction and Cyclooxygenase (COX) Inhibition Activity

et al. 2013

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Cyclooxygenase-2 (COX-2) inhibitors have been in the focus of medicinal chemistry for years and many compounds exhibiting high selectivity and affinity were developed. As carbaboranes represent interesting pharmacophores as phenyl mimetics in drug development, this paper presents the synthesis of carbaboranyl derivatives of COX-2-selective 2,3-disubstituted indoles. Despite the lability of carbaboranes under reducing conditions, 2-carbaborane-3-phenyl-1H-indoles could be synthesized by McMurry cyclization of the corresponding amides. While the meta-carbaboranyl-substituted derivatives (3a-c) lacked COX inhibition activity, the ortho-carbaboranyl analog (3d) was active but showed a selectivity shift towards COX-1.

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Section: Resultsmentioning

confidence: 99%

2‐Carbaborane‐3‐phenyl‐1H‐indoles—Synthesis via McMurry Reaction and Cyclooxygenase (COX) Inhibition Activity

et al. 2013

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“…The studies demonstrated the presence of hydrophobic cavity which is lined by Tyr 385 , Trp 387 , Leu 384 and Met 522 and the unsubstituted phenyl ring positions in this cavity. Presence of methyl or methoxy substitutes on para position of the phenyl ring enhances hydrophobic interaction with the enzyme and therefore increases compound potency (36,53). We found a quadratic effect for liphophilicity, which indicates that it should have an optimum value.…”

Section: Resultsmentioning

confidence: 99%

Exploring QSAR for Substituted 2‐Sulfonyl‐Phenyl‐Indol Derivatives as Potent and Selective COX‐2 Inhibitors Using Different Chemometrics Tools

et al. 2008

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Selective inhibition of cyclooxygenase-2 inhibitors is an important strategy in designing of potent anti-inflammatory compounds with significantly reduced side effects. The present quantitative structure-activity relationship study, attempts to explore the structural and physicochemical requirements of 2-sulfonyl-phenyl-indol derivatives (n = 30) for COX-2 inhibitory activity using chemical, topological, geometrical, and quantum descriptors. Some statistical techniques like stepwise regression, multiple linear regression with factor analysis as the data preprocessing (FA-MLR), principal component regression analysis, and genetic algorithms partial least squares analysis were applied to derive the quantitative structure-activity relationship models. The generated equations were statistically validated using cross-validation and external test set. The quality of equations obtained from stepwise multiple linear regression, FA-MLR, principal component regression analysis and PLS were in the acceptable statistical range. The best multiple linear regression equation obtained from factor analysis (FA-MLR) as the preprocessing step could predict 77.5% of the variance of the cyclooxygenase-2 inhibitory activity whereas that derived from genetic algorithms partial least squares could predict 84.2% of variances. The results of quantitative structure-activity relationship models suggested the importance of lipophilicity, electronegativity, molecular area and steric parameters on the cyclooxygenase-2 inhibitory activity.

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“…For reliability of the model, we have calculated regression-associated statistical parameter called probable error of correlation (PE) (26). In model-1, the value of coefficient of correlation is significantly higher than 6PE, supporting reliability and goodness (19).…”

Section: Resultsmentioning

confidence: 90%

“…To further access the robustness and statistical confidence of the model, bootstrapping analysis was performed (19). In our study, the bootstrapping analysis data of each expressions fall within the agreement (Table 2).…”

Section: Resultsmentioning

confidence: 99%

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2‐(pyrazin‐2‐yloxy)acetohydrazide Analogs QSAR Study: An Insight into the Structural Basis of Antimycobacterial Activity

Gupta

Gupta²,

Soni

et al. 2010

Chem Biol Drug Des

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Quantitative structure activity relationship analysis based on classical Hansch approach was adopted on reported novel series of 2-(pyrazin-2-yloxy)acetohydrazide analogs. Various types of descriptors like topological, spatial, thermodynamic, and electronic were used to derive a quantitative relationship between the antitubercular activity and structural properties. The consensus scoring function showed a significant statistics of training and test set. Coefficient of determination (r 2 ) of consensus model and predictive squared correlation coefficient (r 2 pred ) were found to be 0.889 and 0.782, respectively. The model is not only able to predict the activity of test compounds but also explained the important structural features of the molecules in a quantitative manner. The study revealed that antimycobacterium activity is predominantly explained by the molecular connectivity indices of length 6, hydrogen donor feature of the analogs, and shape factors of the substituent. The comparative investigation of antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Salmonella typhi provided structural insights on how modulation of the molecular connectivity indices, energy of lowest unoccupied molecular orbital, accessible surface area, and moment of inertia of the analogs could be usefully made to optimize the antibacterial activity.

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Exploration of physicochemical properties and molecular modelling studies of 2-sulfonyl-phenyl-3-phenyl-indole analogs as cyclooxygenase-2 inhibitors

Cited by 26 publications

References 24 publications

2‐Carbaborane‐3‐phenyl‐1H‐indoles—Synthesis via McMurry Reaction and Cyclooxygenase (COX) Inhibition Activity

2‐Carbaborane‐3‐phenyl‐1H‐indoles—Synthesis via McMurry Reaction and Cyclooxygenase (COX) Inhibition Activity

Exploring QSAR for Substituted 2‐Sulfonyl‐Phenyl‐Indol Derivatives as Potent and Selective COX‐2 Inhibitors Using Different Chemometrics Tools

2‐(pyrazin‐2‐yloxy)acetohydrazide Analogs QSAR Study: An Insight into the Structural Basis of Antimycobacterial Activity

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