Revisiting the Hansch–Fujita approach and development of a fundamental QSAR

Hitaoka, Seiji; Chuman, Hiroshi

doi:10.1584/jpestics.d12-082

Cited by 11 publications

(6 citation statements)

References 31 publications

(42 reference statements)

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“…As in other fields related to nanosafety, the development of QSAR/QSPR models has been guided by a trade-off between predictive performance and interpretability. On one side, the model can comprise trivial molecular descriptors, such as physicochemical properties, and present a simple learning method such as linear regression [ 190 ]. On the other side, the model can contain continuous and data-driven molecular descriptors, which offer high predictive power and present complex black-box approaches such as artificial neural networks [ 191 ].…”

Section: In Silico Tools In Nanotoxicologymentioning

confidence: 99%

Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment

et al. 2022

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The use of nanomaterials has been increasing in recent times, and they are widely used in industries such as cosmetics, drugs, food, water treatment, and agriculture. The rapid development of new nanomaterials demands a set of approaches to evaluate the potential toxicity and risks related to them. In this regard, nanosafety has been using and adapting already existing methods (toxicological approach), but the unique characteristics of nanomaterials demand new approaches (nanotoxicology) to fully understand the potential toxicity, immunotoxicity, and (epi)genotoxicity. In addition, new technologies, such as organs-on-chips and sophisticated sensors, are under development and/or adaptation. All the information generated is used to develop new in silico approaches trying to predict the potential effects of newly developed materials. The overall evaluation of nanomaterials from their production to their final disposal chain is completed using the life cycle assessment (LCA), which is becoming an important element of nanosafety considering sustainability and environmental impact. In this review, we give an overview of all these elements of nanosafety.

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Section: In Silico Tools In Nanotoxicologymentioning

confidence: 99%

Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment

et al. 2022

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“…In this, the minimum concentration (C) of the drug necessary to obtain a certain level of activity is plotted along the y axis as -logC, and the hydrophobicity is plotted along the x axis as logP, P being the octanol/water partition coefficient for the drug. Whilst a, b and c are constants, σ is the Hammett substituent constant, indicating that the equation can be a linear free energy relationship [28].…”

Section: The Hansch Equation Its Anomalies and Qsarmentioning

confidence: 99%

The Hydrophobic Effect in Chemistry, Biology and Medicine: An Update

Chandrasekhar

2021

AJOCS

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The roots of the hydrophobic effect (HE) apparently lie in certain chemical principles, although it has far-reaching implications across a swath of chemical biology. In particular, the HE drives the formation of micelles, the catalytic properties of which are believed to model the action of enzymes. The HE is also believed to be the key to drug-receptor interactions as captured in the Hansch equation and enshrined in QSAR. Yet, the HE remains paradoxical: The attributed medium effects apparently contravene normal experience, as apolar solvents are rarely (if ever) the preferred choice in practice! Indeed, the HE is complex and varied in its manifestations, affecting both structure and reactivity. The latter “kinetic hydrophobic effect” itself exists as “Types 1 and 2”, referring to reactions in water (e.g., Diels Alder) and non-aqueous media (e.g., micelles) respectively. Micellar reactivity also remains mysterious as, apparently, the HE only facilitates the formation of the micelles. The idea that micellar reactivity arises from concentration effects, in fact, appears simplistic for several reasons. Furthermore, reactions may well occur on the micellar surface, particularly with ionic reagents that would be poorly soluble in the core. There are important differences between micelles and enzymes: Enzymes are pre-configured with catalytic groups and charge-relay systems, although the contribution of the HE to activity remains uncertain. Micelles also form a separate phase, hence defining the thermodynamic ground state of the reactants (contrasting with enzymes). Certain aspects of the Hansch equation, particularly the decline of drug activity beyond the “Goldilocks zone” peak, are intriguing. However, a kinetic model of drug-receptor interactions based on the rates of drug binding and release, offers an explanation for the observations, also leading to further insights into the nature of the binding itself.

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“…Details of the formulation of the LERE-QSAR equation and its applications can be found in a review article 67 and reports of case studies, 29,[68][69][70][71] respectively. We provide a brief summary of LERE-QSAR here.…”

Section: Formulation Of the Lere-qsar Equationmentioning

confidence: 99%

“…> 0), [74][75][76] as demonstrated in the previous studies. 67,69 The third assumption is the entropy-enthalpy compensation rule, [77][78][79][80][81] which is expected to effectively hold for the binding of a series of ligands with a protein.…”

Section: Formulation Of the Lere-qsar Equationmentioning

confidence: 99%

A QSAR study on the inhibition mechanism of matrix metalloproteinase-12 by arylsulfone analogs based on molecular orbital calculations

2015

Self Cite

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A binding mechanism between human matrix metalloproteinase-12 (MMP-12) and eight arylsulfone analogs having two types of carboxylic and hydroxamic acids as the most representative zinc binding group is investigated using a quantitative structure-activity relationship (QSAR) analysis based on a linear expression by representative energy terms (LERE). The LERE-QSAR analysis quantitatively reveals that the variation in the observed (experimental) inhibitory potency among the arylsulfone analogs is decisively governed by those in the intrinsic binding and dispersion interaction energies. The results show that the LERE-QSAR analysis not only can excellently reproduce the observed overall free-energy change but also can determine the contributions of representative free-energy changes. An inter-fragment interaction energy difference (IFIED) analysis based on the fragment molecular orbital (FMO) method (FMO-IFIED) leads to the identification of key residues governing the variation in the inhibitory potency as well as to the understanding of the difference between the interactions of the carboxylic and hydroxamic acid zinc binding groups. The current results that have led to the optimization of the inhibitory potency of arylsulfone analogs toward MMP-12 to be used in the treatment of chronic obstructive pulmonary disease may be useful for the development of a new potent MMP-12 inhibitor.

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Revisiting the Hansch–Fujita approach and development of a fundamental QSAR

Cited by 11 publications

References 31 publications

Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment

Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment

The Hydrophobic Effect in Chemistry, Biology and Medicine: An Update

A QSAR study on the inhibition mechanism of matrix metalloproteinase-12 by arylsulfone analogs based on molecular orbital calculations

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