Multivariate QSAR

Ferreira, Márcia M. C.

doi:10.1590/s0103-50532002000600004

Cited by 124 publications

(164 citation statements)

References 11 publications

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“…Due to the relatively small size of the training set (n = 21), the statistical restriction which imposes a limit from four up to five observations (compounds) per descriptor or independent variable (Ferreira, 2002;Tavares, 2004) were respected in this approach and a maximum of four molecular descriptors per model was considered.…”

Section: Methodsmentioning

confidence: 99%

A 2D-QSPR approach to predict blood-brain barrier penetration of drugs acting on the central nervous system

Sá

Pasqualoto

Rangel-Yagui

2010

Braz. J. Pharm. Sci.

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Drugs acting on the central nervous system (CNS) have to cross the blood-brain barrier (BBB) in order to perform their pharmacological actions. Passive BBB diffusion can be partially expressed by the blood/ brain partition coefficient (logBB). As the experimental evaluation of logBB is time and cost consuming, theoretical methods such as quantitative structure-property relationships (QSPR) can be useful to predict logBB values. In this study, a 2D-QSPR approach was applied to a set of 28 drugs acting on the CNS, using the logBB property as biological data. The best QSPR model [n = 21, r = 0.94 (r² = 0.88), s = 0.28, and Q² = 0.82] presented three molecular descriptors: calculated n-octanol/water partition coefficient (ClogP), polar surface area (PSA), and polarizability (α). Six out of the seven compounds from the test set were well predicted, which corresponds to good external predictability (85.7%). These findings can be helpful to guide future approaches regarding those molecular descriptors which must be considered for estimating the logBB property, and also for predicting the BBB crossing ability for molecules structurally related to the investigated set.Uniterms: Two-dimensional quantitative structure-property relationships (2D-QSPR). Calculated n-octanol/water partition coefficient (ClogP). Blood-brain barrier. Benzodiazepines.Fármacos que atuam no sistema nervoso central (SNC) devem atravessar a barreira hematoencefálica (BHE) para exercerem suas ações farmacológicas. A difusão passiva através da BHE pode ser parcialmente expressa pelo coeficiente de partição entre os compartimentos encefálico e sanguíneo (logBB, brain/blood partition coefficient). Considerando-se que a avaliação experimental de logBB é dispendiosa e demorada, métodos teóricos como estudos das relações entre estrutura química e propriedade (QSPR, Quantitative Structure-Property Relationships) podem ser utilizados na previsão dos valores de logBB. Neste estudo, uma abordagem de QSPR-2D foi aplicada a um conjunto de 28 moléculas com ação central, usando logBB como propriedade biológica. O melhor modelo de QSPR [n = 21, r = 0,94 (r² = 0,88), s = 0,28 e Q² = 0,82] apresentou três descritores moleculares: o coeficiente calculado de partição n-octanol/água (ClogP), área de superfície polar (PSA) e polarizabilidade (α). Seis dos sete compostos do conjunto de avaliação foram bem previstos pelo modelo, o que corresponde a um bom poder de previsão externa (85,7%). Os resultados obtidos podem auxiliar de forma relevante em estudos futuros, orientando quais descritores moleculares devem ser considerados para estimar logBB e prever a passagem através da BHE de moléculas estruturalmente relacionadas às do conjunto investigado. Unitermos:Relações quantitativas bidimensionais entre estrutura química e propriedade (2D-QSPR). Coeficiente calculado de partição n-octanol/água (ClogP). Barreira hematoencefálica. Benzodiazepínicos.

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Section: Methodsmentioning

confidence: 99%

A 2D-QSPR approach to predict blood-brain barrier penetration of drugs acting on the central nervous system

Sá

Pasqualoto

Rangel-Yagui

2010

Braz. J. Pharm. Sci.

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“…Exploratory data analysis comprised two unsupervised methods: hierarchical cluster analysis (HCA) and principal components analysis (PCA) (32,33). HCA and PCA were carried out using Pirouette 3.11 (Infometrix Inc., 1990-2003).…”

Section: Calculation Of Molecular Properties and Exploratory Data Anamentioning

confidence: 99%

“…The distance values were transformed into a similarity matrix whose elements are the similarity indices (similarity kl = 1-d kl /d max , where d max is the largest distance in the data set). The similarity scale ranges from zero (dissimilar samples or variables) to one (identical samples or variables), and the larger the similarity index, the smaller the distance between any pair of samples or variable (32,33). The findings are expressed as a two-dimensional tree named dendrogram.…”

Section: Calculation Of Molecular Properties and Exploratory Data Anamentioning

confidence: 99%

To Be Drug or Prodrug: Structure-Property Exploratory Approach Regarding Oral Bioavailability

et al. 2014

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-Purpose. Prodrug design is a strategy that can be used to adjust physicochemical properties of drugs in order to overcome pharmacokinetic problems, such as poor oral bioavailability. However, Lipinski´s and Veber´s rules predict whether compounds will have absorption problems even before the design of prodrugs. In this context, our goal was to evaluate the molecular properties which most influenced the absorption process of prodrugs compared to its precursor through exploratory data analysis approach. Methods: A variety of prodrugs and respective precursors were randomly selected and classified by its' percentage of human intestinal absorption. Subsequently, different molecular properties were calculated and hierarchical cluster analysis (HCA) and principal components analysis (PCA) were carried out. Results: According to the findings, antiviral, anti-hypertensive, and antibiotic prodrugs exhibited higher absorption levels than their respective precursors. Also, some relevant descriptors (molecular weight, MW, routable bonds, rot_bonds, hydrogen bond acceptors, HBA_count and polar surface area, PSA), which are included in Lipinski´s and Veber´s rules, influenced the separation process between prodrugs and drugs. Furthermore, other molecular properties, such as polarizability (α) and molar refractivity (MR), were pointed out. Conclusion: Lipinski´s and Veber´s rules proved to be important to design an orally administered drug but other descriptors should be considered by medicinal chemists in the prodrug designing process.

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“…The distances between samples or variables are calculated and transformed into a similarity matrix whose elements correspond to the similarity indexes (Ferreira, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…The PCs are completely uncorrelated and are built as a simple linear combination of original variables. Furthermore, the PCs contain most of the variability in the data set within a much smaller dimensional space (Ferreira, 2002).…”

Section: Introductionmentioning

confidence: 99%

Chalcones and N-acylhydrazones: direct analogues? Exploratory data analysis applied to potential novel antileishmanial agents

Rando

Giarolla

Pasqualoto

et al. 2010

Braz. J. Pharm. Sci.

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Leishmaniasis is an important health and social problem for which there is limited effective therapy. Chalcones and N-acylhydrazones have been studied as promising antileishmanial agents in enzymatic inhibition and in vitro assays. Since these chemical classes of compounds also resemble each other structurally, it would be useful to investigate whether they share direct analogy. Exploratory data analysis was applied to a library of chalcones and nitrated N-acylhydrazones assayed against Leishmania donovani to investigate their similarity. Under the conditions applied in the present study, the two classes did not present functional or structural analogy. Uniterms:Chalcones. N-acylhydrazones. Antileishmanial agents. Leishmaniasis. Chemometrics.As leishmanioses são importantes problemas sociais e de saúde pública para os quais a terapia farmacológica atual é, ainda, limitada. Chalconas e N-acilidrazonas têm sido estudadas como promissores agentes leishmanicidas tanto em ensaios in vitro quanto em ensaios de inibição de cisteíno-proteases importantes para o parasito. Uma vez que estas classes de compostos apresentam similaridade bidimensional, seria interessante estudar se estes compostos guardariam relação de analogia direta entre si. Análise exploratória de dados foi aplicada, então, à biblioteca de chalconas e N-acilidrazonas nitradas ensaiadas contra Leishmania donovani para investigar suas relações de similaridade. Os resultados mostraram que, ao menos sob as condições consideradas neste estudo, as duas classes de compostos não apresentam analogia estrutural e funcional simultaneamente, embora elas apresentem alguma similaridade estrutural. Unitermos:Chalconas. N-acilidrazonas. Agentes leishmanicidas. Leishmaniose. Quimiometria.

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Multivariate QSAR

Cited by 124 publications

References 11 publications

A 2D-QSPR approach to predict blood-brain barrier penetration of drugs acting on the central nervous system

A 2D-QSPR approach to predict blood-brain barrier penetration of drugs acting on the central nervous system

To Be Drug or Prodrug: Structure-Property Exploratory Approach Regarding Oral Bioavailability

Chalcones and N-acylhydrazones: direct analogues? Exploratory data analysis applied to potential novel antileishmanial agents

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