Julio Lopes

Federal University of Minas Gerais | UFMG · Departamento de Química

Insulin-like growth factor 1 receptor (IGF1R) acts as a critical mediator of cell proliferation and survival. Many single nucleotide polymorphisms (SNPs) found in the IGF1R gene have been associated with various diseases, including both breast and prostate cancer. The genetics of these diseases could be better understood by knowing the functions of...

A new metric for the evaluation of model performance in the field of virtual screening and quantitative structure–activity relationship applications is described. This metric has been termed the power metric and is defined as the fraction of the true positive rate divided by the sum of the true positive and false positive rates, for a given cutoff...

This paper reports the in silico prediction of biological activities of lignans from Diphylleia cymosa and Podophyllum hexandrum combined with an in vitro bioassays. The extracts from the leaves, roots and rhizomes of both species were evaluated for their antibacterial, anticholinesterasic, antioxidant and cytotoxic activities. A group of 27 lignan...

In the present study, the ethanolic extract from aerial parts of Ageratum fastigiatum was evaluated in vitro against epimastigote forms of Trypanosoma cruzi (Y strain), promastigote forms of Leishmania amazonensis (PH8 strain), and L. chagasi (BH400 strain). The extract was also evaluated against Staphylococcus aureus (ATCC 25 923), Escherichia col...

In this work, we introduced 3D-Pharma, a new Ligand-Based Virtual Screening method that uses fingerprints of pharmacophore triplets at atomic resolutions to build very simple and predictive models. Within 3D-Pharma the molecules are described by multiple representations that comprehend several prototropic species and conformations (multiple species...

Berenil, an anti-trypanosomal agent, is a dicationic bis-benzamidine that has been classified as a minor groove binding ligand in AT-rich regions of DNA. However, previous studies have suggested that berenil can bind to various DNA double strands exhibiting both intercalative and minor groove binding modes. In this work we present a biophysical stu...

Analysis of ligand-protein structures can elucidate many biological mechanisms and guide molecular docking studies. Intermolecular interactions can be encoded in different ways. Binary vectors that represent that information can be called “interaction fingerprints,” and working with them is a good strategy to work with a large set of structures. We...

NEQUIM Contact System (NCS) is a system to generate and analyze interaction vectors of protein-ligand complexes. Core features include multiple views of vectors, multiple selection options, cluster analysis and the generation of interaction vector models. The input could be from a PDB format or from files generated by automatic docking softwares Au...

Motivation: The presence of nsSNPs in genes encoding drug targets, or drug metabolizing enzymes has been increasingly associated with drug response and diseases. The use of computational tools to analyze sequence and structure data of proteins can contribute to increase prediction efficiency of the impact caused by these nsSNPs. Results: We have de...

Silver complexes containing 1,10-phenanthroline as a coordinated ligand have been of great interest due to their antibacterial and antifungal pharmacological properties. In this paper, we describe the synthesis of a new partial inclusion complex of bis(1,10-phenanthroline)silver(I) salicylate in β-cyclodextrin (β-CD) which was synthesized with a go...

Ethanolic (EB) extract and hexanic (SH) and hydromethanolic (SEM) sub-extracts of Humulus lupulus leaves were submitted to cytotoxicity evaluation and to phytochemical methods. The effect of EB and SEM on cellular cycle was evaluated by propidium iod-ide method and the phases were quantified through flow cytom-etry. The cytotoxicity assessment was...

Background Malaria greatly affects the world health, having caused more than 228 million cases only in 2018. The emergence of drug resistance is one of the main problems in its treatment, demonstrating the urge for the development of new antimalarial drugs. Objective Synthesis and in vitro antiplasmodial evaluation of triazole compounds derived fr...

Scientific research based on medicinal plants has been highlighted as a complementary treatment to T2DM, stand out the Vochysiaceae family, which have been widely used in folk medicine by traditional South American communities to treat some diseases. Our study aimed to investigate the antioxidant and antiglycation activities of ethanol extracts of...

Aspidosperma subincanum Mart. (Apocynaceae), conhecida popularmente como guatambu, é utilizada pela população para tratar diabetes mellitus, hipercolesterolemia, problemas gástricos e doenças cardiovasculares1. Várias espécies de Aspidosperma tem apresentado atividade antiprotozoaria. O número de casos de leishmanioses vem crescendo no Brasil e as...

This paper reports the in silico prediction of biological activities of lignans from Diphylleia cymosa and Podophyllum hexandrum combined with an in vitro bioassays. The extracts from the leaves, roots and rhizomes of both species were evaluated for their antibacterial, anticholinesterasic, antioxidant and cytotoxic activities. A group of 27 lignan...

Abstract Ethnopharmacological relevance Leishmaniasis is a parasitic disease that affects people all over the world. The number of cases of leishmaniasis is increasing and the drugs used for its treatment are toxic and not always effective. The recognition of the global nature of this disease and its direct or indirect effects on health economics a...

Ethnopharmacological relevance: Species of Aspidosperma are known popularly as "peroba, guatambu, carapanaúba, pau-pereiro" and "quina". The genus can be found in the Americas, mainly between Mexico and Argentina. Many species of Aspidosperma are used by the population in treating cardiovascular diseases, malaria, fever, diabetes and rheumatism. T...

The new triterpene friedelan-1,3,21-trione, the known compounds friedelan-3-one, 3β-friedelinol, 3,4-seco-friedelan-3-oic acid, 28-hydroxyfriedelan-3-one, friedelan-3-oxo28-al, friedelan-3,21-dione, 30-hydroxyfriedelan-3-one, a mixture of 30-hydroxyfriedelan3-one/21α-hydroxyfriedelan-3-one, 21β-hydroxyfriedelan-3-one, gutta-percha, squalene, and a...

Considerando o uso sustentável da biodiversidade mineira e a busca de substancias com atividade biológica, o sistema Active-IT, tem sido utilizado para identificar novas atividades biológicas potenciais visando o direcionamento de testes que serão realizados, seja com extratos brutos ou substâncias isoladas. Uma base de dados de modelos preditivos...

A espécie Croton urucurana Baill. (Euphorbiaceae) é conhecida popularmente como Sangra D’agua e utilizada na medicina tradicional para tratamento do reumatismo e na cura de feridas1 . Visando a identificação de novas substâncias bioativas, o extrato etanólico das folhas e suas frações foram avaliados em diferentes modelos in vitro para determinação...

Aspidosperma subincanum (Apocynaceae) e conhecida popularmente como guatambu sendo usada pela população para tratar doenças como diabetes mellitus, hipercolesterolemia, entre outras1. Varios alcaloides indolicosbioativos já foram isolados desta especie2. O objetivo deste trabalho foi avaliar diferentes atividades biológicos do extrato e frações de...

Species of Aspidosperma are traditionally used to treat malaria, leishmaniasis, microbial, and inflammatory diseases. Aspidosperma subincanum Mart. known as “guatambu” is used in Brazilian traditional medicine to treat diabetes, hypercholesterolemia, and digestive diseases. Its tonic properties have been employed by the indigenous populations to st...

Strategic planning and computer-aided prediction were used for the synthesis of new bis-hydrazones, which show relevant cytotoxic activity, being promising anticancer agents Abstract Among several possible novel bioactive compounds, hydrazones provide a rich platform for the design of novel bioactive compounds. They are easily synthesized and show...

Lupeol, a triterpene frequently found in Asteraceae plant species, showed moderate to low activity in different strains of Plasmodium falciparum, the most virulent malaria etiological agents. In this work, lupeol was isolated from Parahancornia fasciculata, a plant that is used to treat malaria in the Amazonia region. In the search of more activity...

The Active-IT is an in house system for large scale prediction of biological activities containing about 4000 predictive models based on high quality datasets downloaded from PubChem Bioassay and ChEMBL databases. The models were built with support vector machine (SVM) and Naïve Bayes methods and using 3D pharmacophore fingerprints as molecular des...

Neste trabalho os alcalóides isolados de A. subincanum foram submetidos à análise para a predição de atividades biológicas potenciais utilizando o sistema Active-IT, desenvolvido no Laboratório do Núcleo de Estudos de Quimioinformática (NEQUIM) do Departamento de Química da UFMG, com o objetivo de identificar novas atividades biológicas potenciais...

The work of the molecular modeling can be divided in three equally important steps. The first one is the choice of the descriptors that must be able to describe accurately the properties studied. The second one is modeling method that must be planned carefully to produce the response we are looking for. Finally, the validation process that need to...

Objective: The in silico free access web tools PASS online and ChemMapper were used to predict potential biological activities of compounds 1 to 8 isolated from Maytenus gonoclada (Celastraceae). The constituents 4’-O-methylepigalocatequin (6), tingenone (7) and proanthocyanidin A (8), and ethanolic extracts were subjected to in vitro cytotoxicity...

In this work we investigated the impact of multiple tautomeric forms of chemical compounds in 2D and 3D ligand-based virtual screening studies. We used as a benchmark the DUD database (dud.docking.org) which contains datasets for 40 biological targets, each one with a set of actives and decoys carefully picked to avoid trivial classifications. In t...

The target identification is the first step on drug discovery pipeline. Thus, techniques which address the selection of potential “druggable targets” and potential “therapeutical targets” are very relevant to the discovery of new drugs and therapies. Nowadays, public databases with drug target indication provide target similarity searching based on...

The study of drug target similarity can provide valuable guidelines on target identification, drug repurposing, and rational drug development strategies. Here, we develop a measure of similarity by using singular value decomposition and rank reduction over a vector space originally described by the functional annotation of known drug targets. We sh...

Biscationic amidines bind in the DNA minor groove and present biological activity against a range of infectious diseases. Two new biscationic compounds (bis-α,ω-S-thioureido, amino and sulfide analogues) were synthesized in good yields and fully characterized, and their interaction with DNA was also investigated. Isothermal titration calorimetry (I...

The in vitro antifungal activity of four organosulfur (PD1.1–1.4) and six organophosphorus compounds (PD2.1–2.6) against Candida spp.(C. albicans, C. glabrata and C. krusei), was evaluated. All compounds were easily synthesized in good yields with complete characterisation (FT-IR, MS, 1H/13C NMR). Susceptibility assays were performed according to t...

The present work shows the in vitro antifungal activity studies with eight bis-a,x-S-thioureido functionalized compounds (X-((CH2)n-SC = NR-NHR)2-PD3.1–PD3.8) against Candida spp. (C. albicans, C. glabrata and C. krusei). All compounds were synthesized in good yields and they were fully characterised (FT-IR, MS, 1H/13C NMR). Susceptibility assays w...

The pharmaceutical industry is going through a crisis of unheard proportions. Its cause can be related to the abrupt fall of new molecular entities approval by regulatory agencies, aggravated by the proximity of the expiration date of highly profitable classes of patented compounds and the increasing aggregated cost of drug design. The innovation o...

Drug target identification and validation are critical steps in the drug discovery pipeline. Hence, predicting potential “druggable targets”, or targets that can be modulated by some drug, is very relevant to drug discovery. Approaches using structural bioinformatics to predict “druggable domains” have been proposed, but they have only been applied...

Biscationic amidines bind in the DNA minor groove and present biological activity against a range of infectious diseases. Two new biscationic compounds (bis-α,ω-S-thioureido, amino and sulfide analogues) were synthesized in good yields and fully characterized, and their interaction with DNA was also investigated. Isothermal titration calorimetry (I...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Recebido em 5/10/09; aceito em 26/3/10; publicado na web em 20/7/10 QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) STUDIES OF BISBENZAMIDINES WITH ANTIFUNGAL ACTIVITY. This paper describes 2D-QSAR and 3D-QSAR studies against Candida albicans and Cryptococcus neofarmans for a set of 20 bisbenzamidines. In the studies of 2D-QSAR with C. albican...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The study on reactivity of several α-substituted α-sulfonyl malonates toward 1,4-diazabicyclo[2.2.2]octane (DABCO) and Bu3N is described. The reactivity with DABCO revealed the possible competition between decarbalkoxylation and unexpected desulfonylation, depending on the α-substituent, because of sterical hindrance around the electrophilic center...

Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation between humans, and have the potential to affect gene function, especially when they are located in coding or regulatory regions. Among the many types of SNPs, nonsynonymous SNPs (nsSNPs) are believed to have the greatest impact on protein function, often being ass...

CDK2 of these proteins regulate the cell cycle of various cells. This study is about cyclin-dependent kinases (CDKs) using two different approaches. In the first part of the analysis was the comparison of sequences of active sites several types of CDKs. It analyzed the aminoacids in conserved positions in active sites of CDKs and contacts with liga...

This paper describes 2D-QSAR and 3D-QSAR studies against Candida albicans and Cryptococcus neofarmans for a set of 20 bisbenzamidines. In the studies of 2D-QSAR with C. albicans it was obtained a correlation between log MIC-1 and lipolo component-Z (r2 = 0.68; Q2 = 0.51). In the case of C. neofarmans a correlation between log MIC-1 and lipolo compo...

In this article, we describe a novel methodology to extract semantic characteristics from protein structures using linear algebra in order to compose structural signature vectors which may be used efficiently to compare and classify protein structures into fold families. These signatures are built from the pattern of hydrophobic intrachain interact...

In this study, we carried out a comparative analysis between two classical methodologies to prospect residue contacts in proteins: the traditional cutoff dependent (CD) approach and cutoff free Delaunay tessellation (DT). In addition, two alternative coarse-grained forms to represent residues were tested: using alpha carbon (CA) and side chain geom...

The in situ DNA-damaging capacity of berenil (1) has been investigated usingan electrochemical approach employing double stranded (ds) DNA-modified glassy carbonelectrode biosensors. Electrochemical voltammetric sensing of damage caused by 1 todsDNA was monitored by the appearance of peaks diagnostic of the oxidation of guanineand adenine. When 1 w...

The construction of a realistic theoretical model of proteins is determinant for improving the computational simulations of their structural and functional aspects. Modeling proteins as a network of non-covalent connections between the atoms of amino acid residues has shown valuable insights into these macromolecules. The energy-related properties...

In the present work we develop a new system for inverse docking studies. Our system, called i-BioS (Inverse Biological virtual Screening), is based on Surflex docking program was used to reproduce some of the biological activities of violacein and found new ones, associated to its anti-oxidant character. (http://3dsig.weizmann.ac.il/usersfiles/3dsi...

Serine-proteases are involved in vital processes in virtually all species. They are important targets for researchers studying the relationships between protein structure and activity, for the rational design of new pharmaceuticals. Trypsin was used as a model to assess a possible differential contribution of hydration water to the binding of two s...

The Tropical Biominer Project is a recent initiative from the Federal University of Minas Gerais (UFMG) and the Oswaldo Cruz foundation, with the participation of the Biominas Foundation (Belo Horizonte, Minas Gerais, Brazil) and the start-up Homologix. The main objective of the project is to build a new resource for the chemogenomics research, on...

Some 2-phenylthio-para–substituted cyclohexanones with different oxidation states of sulfur atom were studied by systematic conformational search around C–S bonds using the parametric method 3 (PM3) Hamiltonian. The axial and equatorial regular chair conformations were subjected to calculations and each one produced three rotamers: +gauche (+G), −g...

Drug design strategies based on Comparative Molecular Field Analysis (CoMFA) have been used to predict the activity of new compounds. The major advantage of this approach is that it permits the analysis of a large number of quantitative descriptors and uses chemometric methods such as partial least squares (PLS) to correlate changes in bioactivity...

QSARs are presented for interactions between bis-benzimidazoles and DNA denaturation temperatures and topo-isomerases I and II of Pneumocystis carinii. A Carbo charge and shape similarity index was able to disclose the interaction mode for DNA and topoisomerase II. The global molecular dipole moment descriptor of molecules was found to be the one o...

An important mechanism for some drugs action is by their interaction with genetic material of infecting agent. The formation of drug-DNA complex obstructs the transcription as well DNA replication, inhibiting the multiplication of cell and production of fundamental proteins for its survival. One way for interaction is the drug insertion inside B-DN...

The leishmanicidal drug, meglumine antimoniate (MA), has been synthesized by the reaction of antimony oxyhydrated and N-methyl glucamine. Infrared and solid state NMR 13C analysis of MA and the ligand strongly suggests that antimony binds to N-methyl glucamine through the oxygen of C-3 carbon. Potentiometric titration indicated that, between pH 4.5...

The structure of water (4% D2O in H2O, v/v) solubilized by the reverse aggregates of cetyltrimethylammonium bromide in a chloroform/n-dodecane mixture (6:4, v/v) was probed by FT-IR. The vOD band of solubilized HOD was recorded as a function of the [water]/[surfactant]molar ratio, W/S, from 2.1 to 40.2. Curve fitting of this band showed the presenc...

The structure of water (4% D2O in H2O, v/v) solubilized by the reverse aggregates of cetyltrimethylammonium bromide in a chloroform/n-dodecane mixture (6:4, v/v) was probed by FT-IR. The rOD band of solubilized HOD was recorded as a function of the [water]/[surfactant] molar ratio, W/S, from 2.1 to 40.2. Curve fitting of this band showed the presen...

13C and 1H NMR data for a series of α-halo derivatives of o-xylene are presented. A dynamic 1H NMR investigation of α,α,α′,α′-tetrabromo-o-xylene (5) was performed and the spectrum of the most stable conformer at 213 K is presented. The free energy of activation for the rotation of the CHBr2 groups in 5 are determined for the first time. © 1997 Els...

The νCO IR analysis of α-phenylseleno-p-substituted propiophenones (I) indicates the existence of the cis-gauche rotational isomerism, the gauche conformer is predominant and the more polar one. The carbonyl frequency shifts for the gauche conformer of the title compounds are rather more negative than the δνCO gauche shifts of the previously studie...

The analysis of the vco bands in the IR spectra of the 3-(2′-chlorocyclopentylthio)- and 3-(2′-chloro-1′-methylpropen-1′-ylthio)-thiochromones and their 3-sulfinyl and 3-sulfonyl derivatives, supported by molecular mechanics calculations of 3-methylthio, 3-methylsulfinyl- and 3-methylsulfonyl-thiochromones, taken as model compounds, indicates the e...

The analysis of the carbonyl (ΔνCo) and carbon-carbon double bond (ΔνC[dbnd]C) frequency shifts for some 3-thio-substituted thiochromones and their 3-sulfinyl- and 3-sulfonyl derivatives indicated the occurrence of both πCO/3dSOn and nO(CO)/σC-SOn orbital interactions in the ground state of the title compounds.

The analysis of the v co bands in the IR spectra of the S-ethyl α-heterosubstituted thioacetates helped by Molecular Mechanics Calculations indicated the existence of the cis/gauche rotational isomerism. In the thioacetates series the gauche rotamers predominate over the cis ones. This has been ascribed to the large stabilization of the πco orbital...

Carbonyl stretching frequencies and apparent molar absorptivities are reported for some α-(alkylthio)-acetates, -propionate and -isobutyrate, in the fundamental and 1st overtone regions and compared to those for the corresponding unsubstituted esters. The I.R. data for α-(alkylthio)-esters indicate the cis-gauche rotational isomerism. Both the unus...