QSAR and pharmacophore analysis of thiosemicarbazone derivatives as ribonucleotide reductase inhibitors

Moorthy, N. S. Hari Narayana; Cerqueira, Nuno M. F. S. A.; Ramos, María J.; Fernandes, Pedro A.

doi:10.1007/s00044-011-9580-x

Cited by 13 publications

(7 citation statements)

References 26 publications

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“…The studied molecules and their activity has been given in Table 1 [33,34], andclassified into seven groups for further comparisons and discussion. These groups were: The degree of activity of the molecules could be differentiated through groups; each group have its own activity; related to its composition; for example, when R is hydroxy group (OH) in the position 4, the molecules were active as in the molecules (3,4,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21), but when the hydroxy group was in position 2, the molecules were inactive as in the compounds (1 and 2).…”

Section: Resultsmentioning

confidence: 99%

Quantum Chemical Studies on Some Thiosemicarbazone Derivatives as Ribonucleotide Reductase Inhibitor

Lawar

Badwe

Yalçın

et al. 2018

AJOCS

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QSAR analysis of thiosemicarbazone derivatives exposing RNR inhibitory activities [1] was performed for 21 compounds. Among these compounds, 13 of them were reported with inhibitory concentration (IC 50) in the l M range. The inhibitory concentration of those compounds was converted into-logIC 50 before being correlated with the structural features. The quantum chemical calculations have been carried out at the B3LYP at Complete Basis set (CBS) level of theory using Gaussian-09 series of program package. The density functional theory (DFT), Becke's three parameter exchange function along with the Lee-Yang-Parr correlation function (B3LYP) were considered to calculate the quantum chemical descriptors such as HOMO, LUMO, Energy gap, Hardness, Softness, Chemical potential and Dipole moment of the investigated molecules. The variables make a unique statistically significant contribution (p < 0.05). According to their beta values, electronegativity showed the biggest beta coefficient (-13.225). It has been revealed that variable has a unique contribution to a stronger explanation of dependent variables. Beta values for the electrofugality was slightly lower (8.350) , showing least contribution for rest of the elements. Other variables (Energy gap, chemical potential, nucleofugality) measured for this model was statistically significant.

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Section: Resultsmentioning

confidence: 99%

Quantum Chemical Studies on Some Thiosemicarbazone Derivatives as Ribonucleotide Reductase Inhibitor

Lawar

Badwe

Yalçın

et al. 2018

AJOCS

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“…where C 0 is a constant; a i and b i are regression coefficients; n i is the number of occurrences of the i th atom type in a molecule and B j is the number of occurrences of the j th correction factor [14,29].…”

Section: Y-randomization Resultsmentioning

confidence: 99%

Structural Analysis of 2-Piperidin-4-yl-Actamide Derivatives for hERG Blocking and MCH R1 Antagonistic Activities

Moorthy

Ramos²,

Fernandes³

2012

CDDT

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In the present investigation, a computational based structural analysis was performed on a series of 2-piperidin- 4-yl-acetamide derivatives to investigate the physicochemical features of the molecules responsible for the hERG blocking and melanin concentrating hormone receptor-1 (MCH R1) antagonistic activities. The QSAR models derived from MLR analysis were validated by various validation methods and they provided significant statistical results such as Q(2), F, t(test), R, predicated residual error values, etc. These significant models were constructed with different type of physicochemical descriptors which showed that the hydrophobic properties on the vdW surface of the molecules are favorable for both the activities (MCH R1 antagonistic and hERG blocking activities) and the presence of polar/electronegative groups in the molecules is detrimental for those activities. The presence of flexible aromatic rings in the molecules has favorable hERG blocking activity. The MCH R1 antagonistic activity also depends upon the vdW volume, shape and flexibility of the molecules. In addition, the presented results will guide for the optimized design of novel bioactive molecules with less/free of hERG blocking activities to avoid unwanted potential cardiotoxic side effects related with the use of these possible antiarrhythmic and anti-obesity agents in humans.

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“…the upper limit of the rule of thumb (six cases [compounds] per variable) was adopted in the analysis to reduce overfitting of the descriptors. 17 the significant Qsar models derived from Mlr analysis were selected for further validation studies by taking into account of high correlation coefficients (R or R 2 ), F test and t test values, and the significance of the descriptors included in the model building (variance inflation factor [Vif], durbin-Watson [dW], and beta coefficients). the selected Mlr models were validated to examine the self-consistency between them, which implies a quantitative assessment of the model's robustness and its predictive power.…”

Section: Methodsmentioning

confidence: 99%

“…The upper limit of the rule of thumb (six cases [compounds] per variable) was adopted in the analysis to reduce overfitting of the descriptors. 17…”

Section: Methodsmentioning

confidence: 99%

In Silico–Based Structural Analysis of Arylthiophene Derivatives for FTase Inhibitory Activity, hERG, and Other Toxic Effects

et al. 2011

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In the present investigation, the authors have performed an in silico–based analysis on a series of arylthiophene derivatives for the determination of their structural features responsible for farnesyltransferase (FTase) inhibitory activity, hERG blocking activity, and toxicity by quantitative structure–activity relationship and pharmacophore analysis techniques. The statistically significant models derived through multiple linear regression analysis were validated by different validation methods. The applicability of the descriptors contributed in the selected models show that the polar and polarizable properties on the van der Waals (vdW) surface area of the molecules are important for the FTase inhibitory and hERG blocking activities, while being detrimental for the toxicity of the molecules. It is interesting to note that the topological properties, molecular flexibility, and connectivity of the molecules are positively correlated to all the activities (FTase inhibition, hERG blocking, and toxicity). This implies that the flexibility of the molecules is the common feature for interaction in all targets, whereas the presence of polar groups on the molecular surface (vdW) is a determinant for the favorable (FTase inhibition) or unwanted effect (hERG blocking and toxicity) of the molecules. The pharmacophore analysis of the molecules demonstrated that the aromatic/hydrophobicity and polarizability features are important pharmacophore contours favorable for these activities.

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QSAR and pharmacophore analysis of thiosemicarbazone derivatives as ribonucleotide reductase inhibitors

Cited by 13 publications

References 26 publications

Quantum Chemical Studies on Some Thiosemicarbazone Derivatives as Ribonucleotide Reductase Inhibitor

Quantum Chemical Studies on Some Thiosemicarbazone Derivatives as Ribonucleotide Reductase Inhibitor

Structural Analysis of 2-Piperidin-4-yl-Actamide Derivatives for hERG Blocking and MCH R1 Antagonistic Activities

In Silico–Based Structural Analysis of Arylthiophene Derivatives for FTase Inhibitory Activity, hERG, and Other Toxic Effects

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