Chronic myelogenous leukemia (CML) which is resulted from the BCR-ABL tyrosine kinase (TK) chimeric oncoprotein, is a malignant clonal disorder of hematopoietic stem cells. Imatinib is used as an ...inhibitor of BCR-ABL TK in the treatment of CML patients. The main object of the present manuscript is focused on constructing quantitative activity relationships (QSARs) models for the prediction of inhibition potencies of a large series of imatinib derivatives against BCR-ABL TK. Herren, the inbuilt Monte Carlo algorithm of CORAL software is employed to develop QSAR models. The SMILES notations of chemical structures are used to compute the descriptor of correlation weights (CWs). QSAR models are established using the balance of correlation method with the index of ideality of correlation (IIC). The data set of 306 molecules is randomly divided into three splits. In QSAR modeling, the numerical value of R
, Q
, and IIC for the validation set of splits 1 to 3 are in the range of 0.7180-0.7755, 0.6891-0.7561, and 0.4431-0.8611 respectively. The numerical result of Formula: see text > 0.5 for all three constructed models in the Y-randomization test validate the reliability of established models. The promoters of increase/decrease for pIC
are recognized and used for the mechanistic interpretation of structural attributes.
Extensive dispersal of the pesticides to shield the different types of vegetation from pests has increased the production but at the same it has resulted in an increase in environmental pollution. ...Consequently, it is necessary to eliminate these undesired pollutants from the environment. The current investigation offers the synthesis of humic acid-coated magnetite nanoparticles towards effective removal of the most common insecticide, imidacloprid, from aqueous solution using a batch adsorption method. These synthesized nanoparticles were characterized with the help of several analytical and spectroscopic techniques. To acquire the maximum conceivable adsorption, effects of different influencing parameters like pH of the solution, time of contact, concentration of pesticide solution, amount of adsorbent and temperature were also examined. Moreover, the kinetic studies were found to be in good agreement with a pseudo-second-order kinetic model supporting the occurrence of chemisorption phenomenon. Additionally, isotherm modeling proved that the adsorption process was in accordance with the Langmuir model of isotherm. Thermodynamic parameters depicted the endothermic and spontaneous behavior of the adsorption process. Desorption studies were also carried out to examine the reusability of these nano-adsorbents. These verdicts confirmed that the surface modified magnetite nanoparticles may be treated as proficient material for exclusion of imidacloprid from the aqueous solution.
Cancers are genetically heterogeneous, so anticancer drugs show varying degrees of effectiveness on patients due to their differing genetic profiles. Knowing patient's responses to numerous cancer ...drugs are needed for personalized treatment for cancer. By using molecular profiles of cancer cell lines available from Cancer Cell Line Encyclopedia (CCLE) and anticancer drug responses available in the Genomics of Drug Sensitivity in Cancer (GDSC), we will build computational models to predict anticancer drug responses from molecular features.
We propose a novel deep neural network model that integrates multi-omics data available as gene expressions, copy number variations, gene mutations, reverse phase protein array expressions, and metabolomics expressions, in order to predict cellular responses to known anti-cancer drugs. We employ a novel graph embedding layer that incorporates interactome data as prior information for prediction. Moreover, we propose a novel attention layer that effectively combines different omics features, taking their interactions into account. The network outperformed feedforward neural networks and reported 0.90 for Formula: see text values for prediction of drug responses from cancer cell lines data available in CCLE and GDSC.
The outstanding results of our experiments demonstrate that the proposed method is capable of capturing the interactions of genes and proteins, and integrating multi-omics features effectively. Furthermore, both the results of ablation studies and the investigations of the attention layer imply that gene mutation has a greater influence on the prediction of drug responses than other omics data types. Therefore, we conclude that our approach can not only predict the anti-cancer drug response precisely but also provides insights into reaction mechanisms of cancer cell lines and drugs as well.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Malaria, a nocuous disease, which has become a major challenge for the health resulting in deaths of millions of people around the globe. Malaria is a parasitic disease propagated by mosquitoes and ...infects the human beings. Several species of
Plasmodium
are responsible for this life-threatening disease and
Plasmodium falciparum
being the most virulent. In order to eradicate the malarial parasite, the researchers are making consistent efforts in synthesizing new antimalarial drug candidates by paying attention to the various drug targets. In this manuscript, the main focus is on the antimalarial activity of numerous heterocyclic compounds reported by the researchers since 2010 against the different strains of
Plasmodium
. Antimalarial activities of the two and three nitrogen-containing heterocycles along with their structure–activity relationship are described.
Background
Acyl hydrazones are an important class of heterocyclic compounds promising pharmacological characteristics. Malaria is a life-threatening mosquito-borne blood disease caused by a ...plasmodium parasite. In some places, malaria can be treated and controlled with early diagnosis. However, some countries lack the resources to do this effectively.
Results
The present work involves the design and synthesis of some novel acyl hydrazone based molecular hybrids of 1,4-dihydropyridine and pyrazole (
5a
–
g
). These molecular hybrids were synthesised by condensation of 1,4-dihydropyridin-4-yl-phenoxyacetohydrazides with differently substituted pyrazole carbaldehyde. The final compound (
5
) showed two conformations (the major,
E
,
s
-
cis
and the minor,
E
,
s
-
trans
) as revealed by NMR spectral data and further supported by the energy calculations (MOPAC2016 using PM7 method). All the synthesised compounds were screened for their in vitro antimalarial activities against chloroquine-sensitive malaria parasite
Plasmodium falciparum
(3D7) and antimicrobial activity against Gram positive bacteria i.e.
Bacillus cereus
, Gram negative bacteria i.e.
Escherichia coli
and antifungal activity against one fungus i.e.
Aspergillus niger
. All these compounds were found more potent than chloroquine and clotrimazole, the standard drugs.
Conclusions
In vitro antiplasmodial IC
50
value of the most potent compound
5d
was found to be 4.40 nM which is even less than all the three reference drugs chloroquine (18.7 nM), pyrimethamine (11 nM) and artimisinin (6 nM). In silico binding study of compound
5d
with plasmodial cysteine protease falcipain-2 indicated the inhibition of falcipain-2 as the probable reason for the antimalarial potency of compound
5d
. All the compounds had shown good to excellent antimicrobial and antifungal activities.
Abstract In the current study, tannic acid-functionalized iron oxide nanoparticles have been synthesized using a cost-effective co-precipitation method and subsequently characterized using various ...instrumentation techniques such as Fourier transform infrared spectroscopy, X-ray diffractometer, field emission scanning electron microscopy, and thermal gravimetric analysis. Further, these surface-modified magnetite nanoparticles have been used for the adsorption of toluidine dye from an aqueous solution. The adsorption process was accompanied using batch procedure, and influences of several factors such as adsorbent dose, contact time, pH, temperature, and initial concentration of adsorbate were inspected concurrently. The maximum adsorption capacity of tannic acid-functionalized magnetite nanoparticles was found to be 50.68 mg/g. The adsorption process was observed to follow the Temkin isotherm model, whereas the kinetic study was well described by pseudo-second order. The thermodynamic study revealed the adsorption process to be endothermic and spontaneous in nature with a high degree of freedom between adsorbent and adsorbate. Therefore, the study indicated that the tannic acid-functionalized magnetite nanoparticles have promising adsorption capability and can be used as an excellent adsorbent for the removal of toluidine blue O dye from the aqueous solution.
Iridoids are secondary plant metabolites that are multitarget compounds active against various diseases. Iridoids are structurally classified into iridoid glycosides and non-glycosidic iridoids ...according to the presence or absence of intramolecular glycosidic bonds; additionally, iridoid glycosides can be further subdivided into carbocyclic iridoids and secoiridoids. These monoterpenoids belong to the cyclopentanc-pyran system, which has a wide range of biological activities, including antiviral, anticancer, antiplasmodial, neuroprotective, anti-thrombolytic, antitrypanosomal, antidiabetic, hepatoprotective, anti-oxidant, antihyperlipidemic and anti-inflammatory properties. The basic chemical structure of iridoids in plants (the iridoid ring scaffold) is biosynthesized in plants by the enzyme iridoid synthase using 8-oxogeranial as a substrate. With advances in phytochemical research, many iridoid compounds with novel structure and outstanding activity have been identified in recent years. Biologically active iridoid derivatives have been found in a variety of plant families, including Plantaginaceae, Rubiaceae, Verbenaceae, and Scrophulariaceae. Iridoids have the potential of modulating many biological events in various diseases. This review highlights the multitarget potential of iridoids and includes a compilation of recent publications on the pharmacology of iridoids. Several in vitro and in vivo models used, along with the results, are also included in the paper. This paper's systematic summary was created by searching for relevant iridoid material on websites such as Google Scholar, PubMed, SciFinder Scholar, Science Direct, and others. The compilation will provide the researchers with a thorough understanding of iridoid and its congeners, which will further help in designing a large number of potential compounds with a strong impact on curing various diseases.
Display omitted
•Toxicity of quantum dots is a major concern due to advances in medical applications.•QuasiSMILES has potential for modelling cytotoxicity of quantum dots.•Inclusion of IIC causes the ...building of robust and predictive models.•Consensus modelling improves the predictivity and accuracy of cytotoxicity models.
The assessment of cytotoxicity of quantum dots is very essential for environmental and health risk analysis. In the present work we have modelled HeLa cell cytotoxicity of sixty one CdSe quantum dots with ZnS shell as a function of its experimental conditions and molecular construction using quasiSMILES representations. The index of ideality of correlation helps in the building of ten statistically significant models having good fitting ability with value of R2 ranging from 0.8414 to 0.9609 for the training set. The split 5 model is rated as the best model with values of R2, Q2F1, Q2F2 and Q2F3 as 0.8964, 0.8267, 0.8264 and 0.8777 respectively for the calibration set. The extraction of features causing increase and decrease of cytotoxicity of quantum dots indicates importance of neutral surface charge, surface modified with protein, 72 h exposure time, combination of MTT assay with surface protein in decreasing the cytotoxicity. Amphiphilic polymer, polyol ligand with neutral charge, 0.5 – 0.6 nm quantum dot diameter with lipid ligand and unmodified positively charged surface are grouped in toxicity enhancer features. Further, consensus modelling using split 5 and 8 patterns enhances the prediction quality by increasing the R2val to 0.9361 and 0.9656 respectively.
Obesity has acquired notable attention due to its high occurrence and link with grievous health problems such as hypertension, diabetes and heart disease. It has been reported that the ...endocannabinoid system executes a pivotal part in the management of food absorption, fat augmentation, and energy balance. In the present manuscript, we report a detailed QSAR analysis for 165 CB1 cannabinoid receptor inhibitors employing the Monte Carlo optimization process incorporated within the CORAL software. Eight splits are made from the whole dataset and sixteen QSAR models are developed from these splits employing two target function TF1 (without index of ideality of correlation) and TF2 (with index of ideality of correlation). All the QSAR models developed with TF2 have better predictive potential than the models developed with TF1. The model built for split 5 using TF2 is the leading model due to the higher value of the determination coefficient of the validation set (RValid2 = 0.8518). The index of ideality of correlation (IIC) improves the statistical performance of CORAL-based QSAR-models and gives statistically robust predictive models of the investigated endpoint pIC50. In the present manuscript, a novel criterion “Correlation Contradiction Index (CCI)” is also applied to know its predictive potential. The absolute value of CCI for calibration set is less when QSAR models are developed employing IIC. The promoters of increase and decrease endpoint pIC50 are identified and these are applied to design seven new compounds. All the newly designed molecule were docked into in the active site of human cannabinoid receptor CB1 (PDB ID: 5tgz).
Display omitted
•16 QSAR models for 165 CB1 cannabinoid receptor-inhibitors are developed.•IIC is examined as a criterion of predictive potential.•Correlation Contradiction Index (CCI) is also examined as a criterion of predictive potential.•The absolute value of CCI for calibration set is less when QSAR models are developed employing IIC.•Seven new compounds are designed using the promoters of increase endpoint pIC50.
PDF
