Pain, dietary habits and physical activity of children with developmental disabilities in Croatia, North Macedonia and Serbia: a cross-sectional study.

Background: Multiple studies have shown that children with developmental disabilities (CDD) often live with unrecognized and untreated pain, consume inadequate diet and have inadequate levels of physical activity. This study aimed to analyze pain, dietary habits and physical activity of CDD in Croatia, North Macedonia and Serbia.

Methods: A cross-sectional study was conducted in Croatia, North Macedonia and Serbia in March-April 2023 within the Erasmus+ SynergyEd project.

In silico development of novel angiotensin-converting-enzyme-I inhibitors by Monte Carlo optimization based QSAR modeling, molecular docking studies and ADMET predictions.

Within the realm of pharmacological strategies for cardiovascular diseases (CVD) like hypertension, stroke, and heart failure, targeting the angiotensin-converting enzyme I (ACE-I) stands out as a significant treatment approach. This study employs QSAR modeling using Monte Carlo optimization techniques to investigate a range of compounds known for their ACE-I inhibiting properties. The modeling process involved leveraging local molecular graph invariants and SMILES notation as descriptors to develop conformation-independent QSAR models.

Perceptions on support, challenges and needs among parents and caregivers of children with developmental disabilities in Croatia, North Macedonia and Serbia: a cross-sectional study.

Background: Parents/caregivers of children with developmental disabilities (CDD) have a wide range of support needs and there are various interventions available. Support, challenges, and needs among parents/caregivers of CDD likely vary in different geographical settings. This study aimed to analyze the perceptions of support, challenges, and needs among parents/caregivers of CDD in Croatia, North Macedonia, and Serbia.

Monte Carlo Optimization Method Based QSAR Modeling of Placental Barrier Permeability.

Purpose: In order to ensure that drug administration is safe during pregnancy, it is crucial to have the possibility to predict the placental permeability of drugs in humans. The experimental method which is most widely used for the said purpose is in vitro human placental perfusion, though the approach is highly expensive and time consuming. Quantitative structure-activity relationship (QSAR) modeling represents a powerful tool for the assessment of the drug placental transfer, and can be successfully employed to be an alternative in in vitro experiments.

Development of QSAR model based on Monte Carlo optimization for predicting GABAA receptor binding of newly emerging benzodiazepines.

Benzodiazepines and their derivatives belong to a category of new psychoactive substances that have been introduced into the continually expanding illicit market. However, there is a notable absence of available pharmacological data for these substances. To gain a deeper understanding of their pharmacology, we employed the Monte Carlo optimization conformation-independent method as a tool for developing QSAR models.

Maternal Distress during Pregnancy and the Postpartum Period: Underlying Mechanisms and Child's Developmental Outcomes-A Narrative Review.

Maternal mental health may be considered a determining factor influencing fetal and child development. An essential factor with potentially negative consequences for a child's psychophysiological development is the presence of maternal distress during pregnancy and the postpartum period. The review is organized and presented to explore and describe the effects of anxiety, stress, and depression in pregnancy and the postpartum period on adverse child developmental outcomes.

Development of Novel Therapeutics for Schizophrenia Treatment Based on a Selective Positive Allosteric Modulation of α1-Containing GABAARs-In Silico Approach.

For the development of atypical antipsychotics, the selective positive allosteric modulation of the ionotropic GABAA receptor (GABAAR) has emerged as a promising approach. In the presented research, two unrelated methods were used for the development of QSAR models for selective positive allosteric modulation of 1-containing GABAARs with derivatives of imidazo [1,2-a]-pyridine. The development of conformation-independent QSAR models, based on descriptors derived from local molecular graph invariants and SMILES notation, was achieved with the Monte Carlo optimization method.

In silico approach for the development of novel antiviral compounds based on SARS-COV-2 protease inhibition.

Unlabelled: The COVID-19 pandemic emerged in 2019, bringing with it the need for greater stores of effective antiviral drugs. This paper deals with the conformation-independent, QSAR model, developed by employing the Monte Carlo optimization method, as well as molecular graphs and the SMILES notation-based descriptors for the purpose of modeling the SARS-CoV-3CLpro enzyme inhibition. The main purpose was developing a reproducible model involving easy interpretation, utilized for a quick prediction of the inhibitory activity of SAR-CoV-3CLpro.

Clinically used antifungal azoles as ligands for gold(III) complexes: the influence of the Au(III) ion on the antimicrobial activity of the complex.

In a search for novel antimicrobial metal-based therapeutic agents, mononuclear gold(III) complexes 1-7 of the general formula [AuCl(azole)], where azole stands for imidazole (im, 1), 1-isopropylimidazole (ipim, 2), 1-phenylimidazole (phim, 3), clotrimazole (ctz, 4), econazole (ecz, 5), tioconazole (tcz, 6) and voriconazole (vcz, 7) were synthesized, characterized and biologically evaluated. In all complexes, the corresponding azole ligand is monodentately coordinated to the Au(III) the imidazole or triazole nitrogen atom, while the remaining coordination sites are occupied by chloride anions leading to the square-planar arrangement. antimicrobial assays showed that the complexation of inactive azoles, imidazole, 1-isopropylimidazole and 1-phenylimidazole, to the Au(III) ion led to complexes 1-3, respectively, with moderate activity against the investigated strains and low cytotoxicity on the human normal lung fibroblast cell line (MRC-5).

Neuroinflammation in Autism and Supplementation Based on Omega-3 Polyunsaturated Fatty Acids: A Narrative Review.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction across multiple contexts and restricted, repetitive patterns of behavior, interests and activities. The maternal status of polyunsaturated fatty acids (PUFA) regulates microglial activity and neuroinflammatory pathways during a child's brain development. In children with ASD, the metabolism of PUFA is thought to be deficient or abnormal, leading to increased production of proinflammatory cytokines, increased oxidative stress and an imbalance in the formation and action of neurotransmitters.

In silico development of potential therapeutic for the pain treatment by inhibiting voltage-gated sodium channel 1.7.

The voltage-gated sodium channel Nav1.7 can be considered as a promising target for the treatment of pain. This research presents conformational-independent and 3D field-based QSAR modeling for a series of aryl sulfonamide acting as Nav1.

Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential.

Copper(II) and zinc(II) complexes with clinically used antifungal drug fluconazole (fcz), {[CuCl(fcz)]5HO}, , and {[ZnCl(fcz)]·2CHOH}, , were prepared and characterized by spectroscopic and crystallographic methods. The polymeric structure of the complexes comprises four fluconazole molecules monodentately coordinated via the triazole nitrogen and two chlorido ligands. With respect to fluconazole, complex showed significantly higher antifungal activity against and .

SARS-CoV M inhibitory activity of aromatic disulfide compounds: QSAR model.

The main protease (M) of SARS-associated coronavirus (SARS-CoV) had caused a high rate of mortality in 2003. Current events (2019-2020) substantiate important challenges for society due to coronaviruses. Consequently, advancing models for the antiviral activity of therapeutic agents is a necessary component of the fast development of treatment for the virus.

In silico development of anesthetics based on barbiturate and thiobarbiturate inhibition of GABA.

The inhibition of GABA can be used in general anesthesia. Although, barbiturates and thiobarbiturates are used in anesthesia, the mechanism of their action hasn't been established. QSAR modeling is a wieldy used technique in these cases and this study presents the QSAR modeling for a group of barbiturates and thiobarbiturates with determined anesthetic activity.

The Application of the Combination of Monte Carlo Optimization Method based QSAR Modeling and Molecular Docking in Drug Design and Development.

In recent years, one of the promising approaches in the QSAR modeling Monte Carlo optimization approach as conformation independent method, has emerged. Monte Carlo optimization has proven to be a valuable tool in chemoinformatics, and this review presents its application in drug discovery and design. In this review, the basic principles and important features of these methods are discussed as well as the advantages of conformation independent optimal descriptors developed from the molecular graph and the Simplified Molecular Input Line Entry System (SMILES) notation compared to commonly used descriptors in QSAR modeling.

Design and development of novel therapeutics for coronary heart disease treatment based on cholesteryl ester transfer protein inhibition - approach.

Cholesteryl ester transfer protein (CETP) belongs to the group of enzymes which inhibition have the application in the treatment of cardiovascular diseases. This study presents QSAR modeling for a set of compounds acting as CETP inhibitors based on the Monte Carlo optimization with SMILES notation and molecular graph-based descriptors, and field-based 3D modeling. A 3D QSAR model was developed for one random split into the training and test sets, whereas conformation independent QSAR models were developed for three random splits, with the results suggesting there is an excellent correlation between them.

Design and development of novel therapeutics for brucellosis treatment based on carbonic anhydrase inhibition.

Carbonic anhydrase is a metalloprotein, an enzyme with strong inhibition in antibacterial treatment. This study presents QSAR modeling for a series of 41 chemical compounds, 40 sulfonamides and one sulfamate, including 13 clinically tested drugs as carbonic anhydrase inhibitors based on the Monte Carlo optimization with molecular descriptors based on the SMILES notation and local invariants of the molecular graph, and field 3D based methods. Conformation independent QSAR models were developed for three random splits and a 3D QSAR model for one random split into the training and test sets.

The study of the index of ideality of correlation as a new criterion of predictive potential of QSPR/QSAR-models.

Acetylcholinesterase (AChE) inhibitors, dihydrofolate reductase inhibitors (DHFR), Toxicity in Tetrahymena pyriformis (TP), Acute Toxicity in fathead minnow (TFat), Water solubility (WS), and Acute Aquatic Toxicity in Daphnia magna (DM) are examined as endpoints to establish quantitative structure - property/activity relationships (QSPRs/QSARs). The Index of Ideality of Correlation (IIC) is a measure of predictive potential. The IIC has been studied in a few recent works.

Development and design of novel cardiovascular therapeutics based on Rho kinase inhibition-In silico approach.

Rho kinases, one of the best-known members of the serine/threonine (Ser/Thr) protein kinase family, can be used as target enzymes for the treatment of many diseases such as cancer or multiple sclerosis, and especially for the treatment of cardiovascular diseases. This study presents QSAR modeling for a series of 41 chemical compounds as Rho kinase inhibitors based on the Monte Carlo method. QSAR models were developed for three random splits into the training and test set.

Semi-correlations combined with the index of ideality of correlation: a tool to build up model of mutagenic potential.

Mutagenicity is the ability of a substance to induce mutations. This hazardous ability of a substance is decisive from point of view of ecotoxicology. The number of substances, which are used for practical needs, grows every year.

Development of non-peptide ACE inhibitors as novel and potent cardiovascular therapeutics: An in silico modelling approach.

Angiotensin-converting enzyme (ACE) inhibitors have been acknowledged as first-line agents for the treatment of hypertension and a variety of cardiovascular disorders. In this context, quantitative structure-activity relationship (QSAR) models for a series of non-peptide compounds as ACE inhibitors are developed based on Simplified Molecular Input-Line Entry System (SMILES) notation and local graph invariants. Three random splits into the training and test sets are used.

The anesthetic action of some polyhalogenated ethers-Monte Carlo method based QSAR study.

Up to this date, there has been an ongoing debate about the mode of action of general anesthetics, which have postulated many biological sites as targets for their action. However, postoperative nausea and vomiting are common problems in which inhalational agents may have a role in their development. When a mode of action is unknown, QSAR modelling is essential in drug development.

QSPR in forensic analysis - The prediction of retention time of pesticide residues based on the Monte Carlo method.

A method for the prediction of retention indices of pesticides using the Monte Carlo method and with optimal molecular descriptors based on local graph invariants and the SMILES notation of studied compounds has been presented. Quite satisfactory results were obtained with the proposed method, since a robust model with good statistical quality was developed. The predictive potential of the applied approach was tested and the robustness of the model was proven with different methods.

Potent anti-melanogenic activity and favorable toxicity profile of selected 4-phenyl hydroxycoumarins in the zebrafish model and the computational molecular modeling studies.

7-Hydroxy-4-phenylcoumarin (7C) and 5,7-dihydroxy-4-phenylcoumarin (5,7C) have been evaluated as potential anti-melanogenic agents in the zebrafish (Danio rerio) model in comparison to commercially utilized depigmenting agents hydroquinone and kojic acid. 7C and 5,7C decreased the body pigmentation at 5 µg/mL, while did not affect the embryos development and survival at doses ≤50 µg/mL and ≤25 µg/mL. Unlike hydroquinone and kojic acid, 4-phenyl hydroxycoumarins were no melanocytotoxic, showed no cardiotoxic side effects, neither caused neutropenia in zebrafish embryos, suggesting these compounds may present novel skin-whitening agents with improved pharmacological properties.