J. Vicente de Julian-Ortiz

University of Valencia | UV · Physical Chemistry

The design of fungicides is a central topic in agricultural chemistry. In this manuscript, it is shown how the Superposition of Significant Interaction Rules (SSIR) method can serve the generation of new potentially active molecules. By using SSIR, it is shown how the process becomes a simple symbolic procedure without the intervention of sophistic...

A method to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC) is developed. A set of structurally heterogeneous agents against MTBC was used to obtain a mathematical model based on topological descriptors. This model was statistically validated through a Leave-n-Out test. It successfully discrimin...

A method is developed to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC). A structurally heterogeneous set of compounds active against MTBC was used to obtain a structural pattern model based on structural invariants. This model was statistically validated through a Leave-n-Out test. It successf...

The drugs used for cancer treatment have many drawbacks, as they damage both tumor and healthy cells and, in addition, they tend to be poorly soluble drugs. Their transport in nanoparticles can solve these problems as these can release the drug into tumor tissues, as well as improve their solubility, bioavailability, and efficacy, reducing their ad...

Background On the occasion of the redefinition of the Avogadro constant in May 2019, a brief history and some didactic reflections on its magnitude are presented. Purpose Some analogies are reviewed and others are suggested to help visualize the extent of its magnitude, and their usefulness is assessed. Design/Method These analogies are set in the...

Graphical Abstract Abstract. Chemical graph theory mainly deals with quantitative structure-activity (QSAR) and structure-property relationships (QSPR) studies. A large number of topological indices have been introduced by various eminent researchers. These MOL2NET, 2021, 7, ISSN: 2624-5078 2 https://mol2net-07.sciforum.net/ are found to be useful...

Traditional laboratory methods to evaluate the properties of chemicals involve a huge amount of animal testing, which represents a very important ethical impact and high costs. The EU Biocidal Products Regulation (BPR) includes specific provisions oriented to reduce animal testing, such as the Art 59, which establishes that the generation of inform...

The Superposing Significant Interaction Rules (SSIR) method is a combinatorial procedure that deals with symbolic descriptors of samples. It is able to rank the series of samples when those items are classified into two classes. The method selects preferential descriptors and, with them, generates rules that make up the rank by means of a simple vo...

The endocrine disruptors are defined as a broad and diverse class of substances of natural or anthropogenic origin with the ability to interfere with some function of the endocrine system and, in doing so, cause adverse effects on an organism or its descendants. Endocrine disruption, associated with pathologies such as cancer, obesity, diabetes, an...

Background: The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein that acts as a receptor of extracellular protein ligands of the epidermal growth factor (EGF/ErbB) family. It has been shown that EGFR is overexpressed by many tumours and correlates with poor prognosis. Therefore, EGFR can be considered as a very interesting therap...

Several experimental properties of alkanes are described by means of multilinear models at the cross-validation level. The models have been obtained considering two main sets of descriptors: mathematically-based and experimental ones. The best models are obtained normally involving one of the two sets. The main goal of this work is to show how the...

ABSTRACT Introduction: The steroid receptor coactivator (SRCs) p160 family are essential in the regulation of gene transcriptional processes during the Estrogen Receptor (ERS) signaling. The disruption of the recruitment of SRCs by agonist-activated ERs through extra-receptor or direct competition on the ligand binding domain could be an unexplored...

The mean molecular connectivity indices (MMCI) proposed in previous studies are used in conjunction with well-known molecular connectivity indices (MCI) to model eleven properties of organic solvents. The MMCI and MCI descriptors selected by the stepwise multilinear least-squares (MLS) procedure were used to perform artificial neural network (ANN)...

La predicción del riesgo de diferentes sustancias químicas, como son aquéllas con actividad biocida, es un aspecto esencial en la evaluación del riesgo por exposición a estas sustancias. Entre los distintos métodos predictivos conocidos destacan los métodos computacionales, los cuales presentan numerosas ventajas frente a ensayos de laboratorio, pe...

This volume is based on different aspects of chemical technology that are associated with research and the development of theories for chemical engineers, helping to bridge the gap between classical analysis and modern, real-life applications. The book provides practical insights into many areas of chemical engineering. This book introduces the cur...

Alzheimer’s disease (AD) is the leading cause of dementia in old people worldwide and one of the leading causes of death in developed countries. The current poor understanding of AD mechanisms makes it difficult to develop novel drugs that could be used to treat effectively this disease. Different enzymes are known to be crucial in the biochemical...

Chemoinformatics methodologies such as QSAR/QSPR have been used for decades in drug discovery projects, especially for the finding of new compounds with therapeutic properties and the optimization of ADME properties on chemical series. The application of computational techniques in predictive toxicology is much more recent, and they are experiencin...

A mini-review of developments in sampling algorithms applied to the design of new catalysts and materials is presented. The data mining technology is increasingly being used in new industrial processes, which require automatic analysis of data and related results to proceed quickly to conclusions. However, for some applications, absolute automation...

The mean molecular connectivity indices (MMCI) proposed and used in previous studies are used here in conjunction with the well-known molecular connectivity indices (MCI) to remodel six properties of organic solvents. The MMCI and MCI descriptors of the multilinear relationships for the six properties, obtained with the multilinear least - squares...

The Superposing Significant Interaction Rules (SSIR) method is revised and implemented. The method is a simple combinatorial procedure, which deals with in situ generated rules among a dichotomized congeneric molecular family, selecting the most probabilistically relevant ones. The mere counting of the number of relevant rules attached to new compo...

Rearrangements and their control are a hot topic in supramolecular chemistry due to the possibilities that these phenomena open in the design of synthetic receptors and molecular machines. Macrocycle aza-scorpiands constitute an interesting system that can reorganize their spatial structure depending on pH variations or the presence of metal cation...

The search for new drug candidates in databases is of paramount importance in pharmaceutical chemistry. The selection of molecular subsets is greatly optimized and much more promising when potential drug-like molecules are detected a priori. In this work, A about one hundred thousand molecules are ranked following a new methodology: a drug/non-drug...

Rearrangements and their control are a hot topic in supramolecular chemistry due to the possibilities that these phenomena open in the design of synthetic receptors and molecular machines. Macrocycle aza-scorpiands constitute an interesting system that can reorganize their spatial structure depending on pH variations or the presence of metal cation...

During the last years, research on coordination chemistry of platinum has aroused great interest due to their potential biological applications. Herein, we report the interaction of PtCI4²⁻ with different polyazacyclophanes containing a pyridine unit as aromatic spacer. Formation of complexes has been studied by ¹H and ¹⁹⁵Pt NMR spectroscopy. Analy...

Molecular modeling and chemoinformatics have been used for decades for the selection and optimization of new compounds with therapeutic properties. The application of these techniques in predictive toxicology is more recent, and they are experiencing an increasingly interest because of the new legal requirements imposed by the EU REACH regulation....

The Titius-Bode relationship, a wave-numbers relationship and a third example, are used to launch a wider discussion about the usefulness or significance of relationships in general and, more particularly about the meanings of QSPR/QSAR, i.e., are the published models mature enough? Is their meaning restricted to their usefulness only or does it ha...

A new type of indices, the mean molecular connectivity indices (MMCI), based on nine different concepts of mean are proposed to model, together with molecular connectivity indices (MCI), experimental parameters and random variables, eleven properties of organic solvents. Two model methodologies are used to test the different descriptors: the multil...

Human Intestinal Absorption (HIA) has been modeled many times by using classification models. However, regression models are scarce. Here, Artificial Neural Networks (ANNs) are implemented for this purpose. A dataset of structurally diverse chemicals with their respective experimental HIA were used to design robust, true predictive and widespread a...

Discerning between the concepts of difficulty and usefulness of a molecular ranking classification is of capital importance in virtual design chemistry. Here, both concepts are viewed from the statistical and practical point of view according to the standard definitions of enrichment and statistical significance p-values. These parameters are usefu...

The Titius-Bode relationship, together with a qualitative example from the Ptolemaic cosmological theory, are used to introduce a brief discussion about, not only the validity of relationships, but also about the predictive character, usefulness, and meaning of QSPR/QSAR studies.

Molecular topology has been applied to the search of QSAR models able to identify the anti-allergic activity of a wide group of heterogeneous compounds. Through the linear discriminant analysis and artificial neural networks, correct classification percentages above 85% for both the training set and the test set have been obtained. After carrying o...

Water intrusion–extrusion in hydrophobic microporous AFI, IFR, MTW and TON pure silica zeolites (zeosils) has been investigated through molecular dynamics (MD) simulations. It was found that intruded water volumes correlate with the free volume of the zeosil unit cells. Calculated adsorption isotherms allowed us to estimate the amounts of water int...

In many fields of Chemistry, ordinary or traditional Least Squares fitting method (LS) is preferentially used to fit data, especially in QSAR/QSPR and in many scientific and chemistry-related fields. Nevertheless, least-squares univariate linear regression analysis has some drawbacks which are usually overlooked. Sometimes, one alternative is to us...

Many of the numerical and algorithmic procedures used in the QSAR/QSPR field lead to rank or to predict activity values for virtual molecules. It is also well known that an image can give more information than a list of numbers. This is the reason why in order to illustrate the results obtained and its performance, several kinds of graphical repres...

In many fields of chemistry, the ordinary least-squares method is preferentially used to fit data. Nevertheless, univariate linear regression by least-squares analysis, as devised by Gauss and Legendre, has some drawbacks that are usually overlooked in experimental science courses and even in many chemical research papers. Orthogonal least-squares...

Interaction of nitrate anions with a cyclophane (L) containing two pyridine units connected to two diethylenetriamine bridges through methylene positions is reported both in pure water and in the solid state. The crystal structure of [H4L](NO3)4 shows that one of the nitrate anions resides in the macrocyclic cavity forming two sets of bifurcated hy...

The investigation of stability of as-made Beta zeolite polymorphs A, B, and C (BEA, BEB, and BEC) was carried out on the basis of lattice energy minimization and molecular dynamic atomistic simulations. The force field employed provided an excellent agreement between calculated and experimental enthalpies of formation of zeolites with respect to qu...

A critical examination of different least squares orthogonal methods (OR1-OR4) and of the ordinary least squares (LS) method, which is normally used in QSAR and QSPR studies, and in many scientific and chemistry-related fields, reveals that not always the orthogonal regression methods perform better than LS in the aforementioned fields. Nonetheless...

Trichomonas vaginalis (Tv) is the causative agent of the most common, non-viral, sexually transmitted disease in women and men worldwide. Since 1959, metronidazole (MTZ) has been the drug of choice in the systemic treatment of trichomoniasis. However, resistance to MTZ in some patients and the great cost associated with the development of new trich...

A wealth of new graph concepts can be encountered in the present developments in mathematical chemistry and chemical graph theory. Such developments extend to chemical kinetics and biomacromolecules. Meanwhile, in the field of physics, absolute theories can predict a certain property of a system from its fundamental parameters without using adjusta...

Marrero-Ponce, Yovani xD;Meneses-Marcel, Alfredo xD;Rivera-Borroto, Oscar M xD;Garcia-Domenech, Ramon xD;De Julian-Ortiz, Jesus Vicente xD;Montero, Alina xD;Escario, Jose Antonio xD;Barrio, Alicia Gomez xD;Pereira, David Montero xD;Nogal, Juan Jose xD;Grau, Ricardo xD;Torrens, Francisco xD;Vogel, Christian xD;Aran, Vicente J xD;Research Support, No...

Regression toward the mean effects are presented within the field of quantitative structure-activity relationship modeling and in situations in which multilinear regression techniques are considered for model building. The concept is related to the graphical aspect of some scatter plots (experimental vs fitted and fitted vs experimental values). Th...

Topological indices have been applied to build QSAR models for a set of 20 an-timalarial cyclic peroxy cetals. In order to evaluate the reliability of the proposed linearmodels leave-n-out and Internal Test Sets (ITS) approaches have been considered. The pro-posed procedure resulted in a robust and consensued prediction equation and here it isshown...

A database of structurally heterogeneous chemical structures with their experimental values of Lowest Observed Adverse Effect Levels (LOAELs) was modeled using graph theoretical descriptors. Variable selection for multiple linear regression (MLR) and linear discriminant analysis (LDA) was accomplished by the Internal Test Set (ITS) method in order...

An interesting and often overlooked property of the MLR least-squares method is discussed. Here it is shown how the observed vs. calculated and calculated vs. observed plots, which are usually presented as equivalent, in fact they are not. Due to the inherent properties of the MLR procedure, it is shown that the slope of the calculated vs. observed...

A quantitative structure-activity relationship study using a database of 395 compounds previously tested against chloroquine-susceptible strains of the blood stages of Plasmodium falciparum to predict new in vitro antimalarial drugs has been developed. Topological indices were used as structural descriptors and were related to antimalarial activity...

Motivation. The main goal of the present work is selecting new cytostatic lead compounds through molecular topology. This is particularly interesting since the finding of new therapeutic alternatives for cancer continues to be a very difficult task as demonstrated by the low number of lead drugs approved by the international agencies in the later y...

One of fue most significant differences between fue topological and fue physicochemical description of molecules is that fue first usually makes use of discrete mathematics while fue second handles continuous functions. Thus, molecular topology introduce discrete numbers called topological indices as fue key descriptors, whereas quantum chemistry i...

In many scientific and chemistry-related fields it is very common to represent in a bidimensional plot calculated and observed data in many scientific and chemistry-related fields. If calculated values are obtained via a linear or multilinear regression procedure it will be shown how the two representation choices, fitted vs. observed and observed...

A study on the basis of molecular topology has been carried out to predict the potency of insecticides active against malaria vectors (Culex) as well as to select novel compounds potentially active on those vectors. The results, performed over two sets of compounds, namely hormone-like and ‘common’ or wide-spectra insecticides, demonstrate that the...

To compare the activity of linezolid with a range of drugs used in the treatment of Mycobacterium kansasii infections. The percentages of resistant isolates against isoniazid, rifampicin and ethambutol were 2.9%, 1.9% and 2.9%, respectively. All isolates were susceptible to clarithromycin and moxifloxacin both with MIC(90) values of 0.125 mg/L. Lin...

A database of chronic lowest observed adverse effect levels (LOAELs) for 234 compounds, previously compiled from different sources (Toxicology Letters79, 131-143 (1995)), was modelled using graph theoretical descriptors. This study reveals that data are not homogeneous. Only those data originating from the U.S. Environmental Protection Agency (EPA)...

A method to identify chemical scaffolds potentially active against Mycobacterium tuberculosis is presented. The molecular features of a set of structurally heterogeneous antituberculosis drugs were coded by means of structural invariants. Three techniques were used to obtain equations able to model the antituberculosis activity: linear discriminant...

The complete structural analysis of the palladium complexes of the triolefinic macrocycles (E,E,E)-1,6,11-tris(arylsulfonyl)-1,6,11-triazacyclopentadeca-3,8,13-trienes, which featured from three identical to three different aryl groups, was achieved by performing X-ray diffraction studies, NMR spectroscopy, and other calculations. The stereochemica...

Grounds: The increasing resistance of P. falciparum to conventional drugs forces the search of new alternatives, either therapeutic, or preventive. A promising way is offered by the phosphatidyl choline analogues, which interact with the metabolism of the phospholipids. In the field of the prevention, the design of new more effective insecticides i...

Grounds: The increasing resistance of P. falciparum to conventional drugs forces the search of new alternatives, either therapeutic, or preventive. A promising way is offered by the phosphatidyl choline analogues, which interact with the metabolism of the phospholipids. In the field of the prevention, the design of new more effective insecticides i...

Five residual plots of modelled properties, as well as a random residual plot are analyzed to underline the importance of residual plots in detecting anomalies in the quality of a model. Residual plots can help to detect anomalies, which hide inside tables of modelled properties or activities, and which are not easily detected by the statistical pa...

Five model cases are analyzed to underline the importance and usefulness of plot methods in detecting either anomalies or in confirming the quality of a model, which, normally, are not easily detected by tables or by statistical parameters. Plot methods in QSAR model studies can be as important as spectroscopic methods in many experimental studies.

Multivariate models are reported that can predict the relative toxicity of compounds with severe environmental impact, namely polychloro dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). Multiple linear regression analysis (MLR) and partial least square projections of latent variables (PLS) show the usefulness of graph-theoretical descriptors, m...

In an article of this journal Pecka and Ponec [J. Math. Chem. 27 (2000) 13] have proposed, by means of a probability calculation, a method to evaluate the statistical importance of correlations obtained from multilinear regression equations involving an arbitrary number of experimental points and parameters. Here, it is demonstrated how this probab...

A set of 21 previously published COX-2 inhibitors has been analyzed in order to obtain a new paradigm capable of obtaining true predictions of the activity. Overfitting in the models has effectively been prevented even for small training sets. The most significant variables for the prediction of the property have been selected, and outliers have al...

A QSAR approach based on the use of various topological indices as new theoretical molecular descriptors was applied to the study of a set of 64 anti-tuberculosis agents involving the substituted benzoxazines and phenylquinazolines. In order to evaluate the reliability of the proposed linear QSAR model, several statistical tests were proposed. The...

We used molecular connectivity to search mathematical models for predicting physico-chemical (e.g. the partition coefficient, P), pharmacokinetic (e.g. the time of maximum plasma level, and toxicological properties (lethal dose, LD) for a group of antihistaminic drugs. The results obtained clearly reveal the high efficiency of molecular topology fo...

The generation of diversity and its further selection by an external system is a common mechanism for the evolution of the living species and for the current drug design methods. This assumption allows us to label the methods based on generation and selection of molecular diversity as "Darwinian" ones, and to distinguish them from the structure-bas...

Discriminating "drug-like" from "non-drug-like" compounds is a relatively emerging topic within the drug research. The basic assumption is that it is possible to obtain relevant information from structural features common to the known drugs, in order to discard a huge number of candidate chemical structures with low probability of becoming drugs. A...

Molecular connectivity has been applied to the search of mathematical models able to predict the carcinogenic and teratogenic activity of a wide group of structurally heterogeneous compounds. Through the linear discriminant analysis and the diagrams of distribution of pharmacological activity, the classification criteria that minimizes the percenta...

Discriminating “drug-like” from “non-drug-like” compounds is a relatively emerging topic within the drug research. The basic assumption is that it is possible to obtain relevant information from structural features common to the known drugs, in order to discard a huge number of candidate chemical structures with low probability of becoming drugs. A...

Molecular Topology (M.T.) has demonstrated its efficiency in the prediction of many experimental parameters. The application of the topological indices to the prediction of pharmacological properties, and, above all, to its inverse problem, the drug design, is particularly interesting [1,2]. Several attempts to explain the reasons of such efficienc...

A study is reported of the relationship between theR F values for a group of organophosphorus insecticides obtained by thin layer chromatography and a series of topological descriptors. By using multivariate regression, the corresponding connectivity functions were obtained, which had been selected on the basis of their respective statistical para...

The activity of new anti-HSV-1 chemical structures, designed by virtual combinatorial chemical synthesis and selected by a computational screening, is determined by an in vitro assay. A virtual library of phenol esters and anilides was formed from two databases of building blocks: one with carbonyl fragments and the other containing both substitute...

In this work we carry out a study of pattern recognition to detect the microbiological activity in a group of heterogeneous compounds. The structural descriptors utilized are the topological connectivity indexes. The methods followed are stepwise linear discriminant analysis (linear analysis) and artificial neural network (nonlinear analysis). Alth...

A common assumption in chemistry is that chiral behavior is associated with 3-D geometry. However, chiral information is related to symmetry, which allows the topological handling of chiral atoms by weighted graphs and the calculation of new descriptors that give a weight to the corresponding entry in the main diagonal of the topological matrix. In...

Answers questions raised by related letter. Keywords (Audience): Second-Year Undergraduate

Molecular connectivity has been used to find new β-blocker drugs using linear discriminant analysis and connectivity functions with different topological descriptors. Among the selected compounds stands out the probucol and the β-carotene. Both of them interact with β adrenoceptors.

Molecular topology has been applied to the design of new analgesic drugs. Linear discriminant analysis and connectivity functions were used to design two potentially suitable drugs which were synthesized and tested for analgesic properties by the acetic acid-induced abdominal constriction test in mice and the tail-flick test in rats. In mice, the c...