Variations of VEGFR2 Chemical Space: Stimulator and Inhibitory Peptides.

The kinase pathway plays a crucial role in blood vessel function. Particular attention is paid to VEGFR type 2 angiogenesis and vascular morphogenesis as the tyrosine kinase pathway is preferentially activated. In silico studies were performed on several peptides that affect VEGFR2 in both stimulating and inhibitory ways. This investigation aims to examine the molecular properties of VEGFR2, a molecule primarily involved in the processes of vasculogenesis and angiogenesis. These relationships were defined by the interactions between Vascular Endothelial Growth Factor receptor 2 (VEGFR2) and the structural features of the systems. The chemical space of the inhibitory peptides and stimulators was described using topological and energetic properties. Furthermore, chimeric models of stimulating and inhibitory proteins (for VEGFR2) were computed using the protein system structures. The interaction between the chimeric proteins and VEGFR was computed. The chemical space was further characterized using complex manifolds and high-dimensional data visualization. The results show that a slightly similar chemical area is shared by VEGFR2 and stimulating and inhibitory proteins. On the other hand, the stimulator peptides and the inhibitors have distinct chemical spaces.

New Hydrophilic Matrix Tablets for the Controlled Released of Chlorzoxazone.

The modified release of active substances such as chlorzoxazone from matrix tablets, based on Kollidon®SR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on Kollidon®SR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20-40 w/w % Kollidon®SR, 3-7 w/w % chitosan while the auxiliary substances: Aerosil® 1 w/w %, magnesium stearate 0.5 w/w % and Avicel® up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0-2 h) and the second (2-36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1-the similarity factor, and f2-the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample.

Giant Intraabdominal Lymphangioma in a Pediatric Patient-A Challenging Diagnosis.

Introduction: Intra-abdominal cystic formations represent heterogeneous pathologies with varied localization and clinical manifestation. The first challenge of a giant intra-abdominal cystic lesion is identifying the organ of origin. The clinical presentation of intra-abdominal cystic lesions varies from acute manifestations to non-specific symptoms or accidental discovery. Case presentation: A 2-year-old girl presents to the emergency unit with a fever of 38.5 Celsius, loss of appetite, and apathy. The investigations showed a gigantic intra-abdominal mass whose organ belonging could not be specified. Postoperatively, a giant mesenteric lymphangioma was evident, which was completely excised. Discussion: Giant cystic formations modify the anatomical reports and become space-replacing formations, and the starting point is even more challenging to assess preoperatively. Nevertheless, the careful evaluation of the characteristics of the formation, the effect on the adjacent organs, the age of the patient, and the clinical picture can provide elements of differential diagnosis. The stated purpose of this work is to systematize intra-abdominal lesions according to the organ of origin and to make the preoperative diagnosis of an intra-abdominal cystic lesion in the pediatric patient easy to perform starting from the presented case.

Endovascular Drug Delivery.

Drug-eluting stents (DES) and balloons revolutionize atherosclerosis treatment by targeting hyperplastic tissue responses through effective local drug delivery strategies. This review examines approved and emerging endovascular devices, discussing drug release mechanisms and their impacts on arterial drug distribution. It emphasizes the crucial role of drug delivery in modern cardiovascular care and highlights how device technologies influence vascular behavior based on lesion morphology. The future holds promise for lesion-specific treatments, particularly in the superficial femoral artery, with recent CE-marked devices showing encouraging results. Exciting strategies and new patents focus on local drug delivery to prevent restenosis, shaping the future of interventional outcomes. In summary, as we navigate the ever-evolving landscape of cardiovascular intervention, it becomes increasingly evident that the future lies in tailoring treatments to the specific characteristics of each lesion. By leveraging cutting-edge technologies and harnessing the potential of localized drug delivery, we stand poised to usher in a new era of precision medicine in vascular intervention.

The Influence of Risk Factors in the Early Detection of Developmental Dysplasia of the Hip in a Country with Limited Material Resources.

Developmental dysplasia of the hip (DDH) is a condition that includes a wide spectrum of anomalies ranging from simple instability with ligamentous hyperlaxity to the complete displacement of the femoral head outside the abnormally developed cotyloid cavity. Early detection and initiation of treatment allow "restitutio ad integrum" healing, which has raised the medical community's interest in early diagnosis. However, in countries with limited material resources, where echographic screening is not performed, efforts are being made to increase the sensitivity of clinical screening. Thus, the concept of "hip at risk" is taking shape worldwide. This is the normal clinical hip, but associated with one or more risk factors. We conducted a retrospective study for the period 2010-2015 with patients who presented in the ambulatory clinic of the St. John Children's Clinical Hospital, Galati. The study included 560 patients, who were all examined clinically and sonographically, according to the Graf method, by a senior orthopedic doctor with competence in hip sonography. The data obtained from the anamnesis, clinical examination, and ultrasound examination were recorded in the DDH file. The goal of the statistical analysis of the group of patients was to find a correlation between DDH and the risk factors used in the clinical detection of this pathology. In the studied group, four risk factors were identified that have an increased association with DDH: female sex, pelvic presentation, limitation of coxo-femoral abduction, and congenital clubfoot; thus, the conclusion of the study is that patients who have at least one of the listed risk factors should be examined sonographically as quickly as possible. The early ultrasound examination will allow the identification of the disease and the initiation of treatment.

SARS-CoV-2 Spike Protein Interaction Space.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a +sense single-strand RNA virus. The virus has four major surface proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N), respectively. The constitutive proteins present a high grade of symmetry. Identifying a binding site is difficult. The virion is approximately 50-200 nm in diameter. Angiotensin-converting enzyme 2 (ACE2) acts as the cell receptor for the virus. SARS-CoV-2 has an increased affinity to human ACE2 compared with the original SAR strain. Topological space, and its symmetry, is a critical component in molecular interactions. By exploring this space, a suitable ligand space can be characterized accordingly. A spike protein (S) computational model in a complex with ACE 2 was generated using silica methods. Topological spaces were probed using high computational throughput screening techniques to identify and characterize the topological space of both SARS and SARS-CoV-2 spike protein and its ligand space. In order to identify the symmetry clusters, computational analysis techniques, together with statistical analysis, were utilized. The computations are based on crystallographic protein data bank PDB-based models of constitutive proteins. Cartesian coordinates of component atoms and some cluster maps were generated and analyzed. Dihedral angles were used in order to compute a topological receptor space. This computational study uses a multimodal representation of spike protein interactions with some fragment proteins. The chemical space of the receptors (a dimensional volume) suggests the relevance of the receptor as a drug target. The spike protein S of SARS and SARS-CoV-2 is analyzed and compared. The results suggest a mirror symmetry of SARS and SARS-CoV-2 spike proteins. The results show thatSARS-CoV-2 space is variable and has a distinct topology. In conclusion, surface proteins grant virion variability and symmetry in interactions with a potential complementary target (protein, antibody, ligand). The mirror symmetry of dihedral angle clusters determines a high specificity of the receptor space.

Molecular Motifs in Vascular Morphogenesis: Vascular Endothelial Growth Factor A (VEGFA) as the Leading Promoter of Angiogenesis.

Tissular hypoxia stimulates vascular morphogenesis. Vascular morphogenesis shapes the cell and, consecutively, tissue growth. The development of new blood vessels is intermediated substantially through the tyrosine kinase pathway. There are several types of receptors inferred to be located in the blood vessel structures. Vascular endothelial growth factor A (VEGF-A) is the leading protagonist of angiogenesis. VEGF-A's interactions with its receptors VEGFR1, VEGFR2, and VEGFR3, together with disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), connective tissue growth factor (CTGF), and neuropilin-1 (NRP1), independently, are studied computationally. Peripheral artery disease (PAD), which results in tissue ischemia, is more prevalent in the senior population. Presently, medical curatives used to treat cases of PAD-antiplatelet and antithrombotic agents, statins, antihypertensive remedies with ACE (angiotensin-converting enzyme) impediments, angiotensin receptor blockers (ARB) or ß- blockers, blood glucose control, and smoking cessation-are not effective. These curatives were largely established from the treatment of complaint cases of coronary disease. However, these medical curatives do not ameliorate lower limb perfusion in cases of PAD. Likewise, surgical or endovascular procedures may be ineffective in relieving symptoms. Eventually, after successful large vessel revascularization, the residual microvascular circulation may well limit the effectiveness of curatives in cases of PAD. It would thus feel rational to attempt to ameliorate perfusion in PAD by enhancing vascular rejuvenescence and function. Likewise, stimulating specific angiogenesis in these cases (PAD) can ameliorate the patient's symptomatology. Also, the quality of life of PAD patients can be improved by developing new vasodilative and angiogenetic molecules that stimulate the tyrosine kinase pathway. In this respect, the VEGFA angiogenetic pathway was explored computationally. Docking methodologies, molecular dynamics, and computational molecular design methodologies were used. VEGFA's interaction with its target was primarily studied. Common motifs in the vascular morphogenesis pathway are suggested using conformational energy and Riemann spaces. The results show that interaction with VEGFR2 and ADAMTS1 is pivotal in the angiogenetic process. Also, the informational content of two VEGFA complexes, VEGFR2 and ADAMTS1, is crucial in the angiogenesis process.

Editorial for Special Issue-''Research Progress and Applications of Natural Products".

This Special Issue (S [...].

Benzoquinoline Chemical Space: A Helpful Approach in Antibacterial and Anticancer Drug Design.

Benzoquinolines are used in many drug design projects as starting molecules subject to derivatization. This computational study aims to characterize e benzoquinone drug space to ease future drug design processes based on these molecules. The drug space is composed of all benzoquinones, which are active on topoisomerase II and ATP synthase. Topological, chemical, and bioactivity spaces are explored using computational methodologies based on virtual screening and scaffold hopping and molecular docking, respectively. Topological space is a geometrical space in which the elements composing it can be defined as a set of neighbors (which satisfy a particular axiom). In such space, a chemical space can be defined as the property space spanned by all possible molecules and chemical compounds adhering to a given set of construction principles and boundary conditions. In this chemical space, the potentially pharmacologically active molecules form the bioactivity space. Results show a poly-morphological chemical space that suggests distinct characteristics. The chemical space is correlated with properties such as steric energy, the number of hydrogen bonds, the presence of halogen atoms, and membrane permeability-related properties. Lastly, novel chemical compounds (such as oxadiazole methybenzamide and floro methylcyclohexane diene) with drug-like potential, active on TOPO II and ATP synthase have been identified.

Vaccine Coverage in Children Younger Than 1 Year of Age during Periods of High Epidemiological Risk: Are We Preparing for New Outbreaks?

Background: According to WHO, infectious disease control can be achieved if the vaccine coverage (VC) exceeds 90%. In recent years there has been a declining trend in VC which could lead to the recurrence of infectious diseases. Objectives: The study analyzed the determinants of VC and of parental decisions regarding immunization in children aged 0−1 year monitored during two high-risk epidemiological periods (the measles epidemic and the COVID-19 pandemic period). Methods: A retrospective observational cohort study-data regarding vaccination of children younger than 1 year of age during the periods January 2019−June 2019 (measles epidemic) and January 2020−June 2020 (COVID-19 pandemic) were analyzed. 2.850 children from 2019 and 2.823 children from 2020 were enrolled. Family physicians interacted with 2840 parents or legal guardians in 2019 and with 2800 parents or legal guardians in 2020, during the infants' consults providing medical information and answer to their questions and worries regarding their immunization. Data on immunization schedules on the determinants of parents' decisions regarding vaccination were evaluated. Results: During 2019−2020, VC has followed a declining trend for each type of vaccine included in the Romanian National Immunization Program; the most affected were infants aged 9−12 months during both periods: in 9-month aged infants, the MMR vaccine VC was 67.49% in 2019 vs. 59.04% in 2020 (p < 0.004). In the 12 months aged infants, the MMR VC was 64.29% in 2019 vs. 55.88% in 2020 (p < 0.005). For the Hexavalent vaccine administered at the age of 11 months, the VC was 71.59% in 2019 vs. 62.08% in 2020 (p < 0.001). The determinants of parents' decisions regarding vaccination included parental hesitance 2019­25% vs. 2020­35%, fear on side effects 2019­32% vs. 2020­45%, vaccination denial 2019­7% vs. 2020­10%. Conclusion: We found a declining trend in the VC in Romania during the epidemic and pandemic periods. The decrease in VC for MMR generated a major risk for new measles outbreaks Permanent awareness educational campaigns regarding infectious disease risk are needed, accompanied by the empowerment of primary care and the emergence of an immunization management program based on national regulatory legislation.

Glomangioma Supply from Profunda Femoris Artery in Peripheral Artery Disease.

This is a case report of a 5.6 cm glomangioma supplied by the femoral profunda artery in a 66-year-old male patient with severe peripheral artery disease. The patient complained of discomfort and mild pain at the place of the lesion and an accelerated growth rate in the last two months. A nodular mass located laterally on the left foot, elastic, covered with a thin skin, and mobile, was noted on the clinical exam. Doppler exam demonstrated an active vascular supply. CT angiography showed a femoral profunda artery blood supply and a severe asymptomatic bilateral peripheral artery disease (PAD). The lesion was removed entirely by surgery. A microscopy exam revealed a glomangioma. After surgery, the patient recovered unevenly. However, the patient experienced wound-healing issues that resolved after four weeks of surgery. Although the patient's PAD was severe, the lesion presented with a burst in dimensions weeks before surgery.

Obstetric fractures in caesarean delivery and risk factors as evaluated by paediatric surgeons.

INTRODUCTION: Obstetric fractures usually occur after complicated births and are sent to paediatric orthopaedics for treatment and follow-up. Clavicle fractures represent the most common orthopaedic birth injury, involving approximately 0.2 to 3.5% of births. HYPOTHESES: Caesarean delivery, elective or necessary, along with the type of presentation, may play a determinant role in the aetiology of obstetric fractures. MATERIALS AND METHODS: We chose to do a retrospective study to determine possible risk factors for this type of injury that may manifest in either delivery. Our aim was to deepen our knowledge in order to have a better prediction and a better management of this condition. Data gathered included parity, gestity, type of delivery, presentation, shoulder dystocia, type of fracture, birth weight, and APGAR score. RESULTS: We followed 136 patients that were diagnosed with Allman type I clavicle fracture, 32 of them also having brachial plexus birth palsy (BPBP) type 1 (Duchenne-Erb). Natural birth with a pelvic presentation imposes a relative risk of 6.2 of associated pathology compared to cranial presentation. Caesarean delivery and cranial presentation increase the risk of related pathology by 5.04 compared to natural birth. Statistically, pelvic presentation is 5.54 times more likely to develop related pathology than cranial presentation. Type of delivery and presentation correlate with associated pathology of clavicle fractures. DISCUSSION AND CONCLUSION: Caesarean delivery brings risks for the newborn and should be practiced only when necessary. Predictive modeling in obstetrics in third-trimester evaluations may statistically predict risks of birth complications like fracture and BPBP.

Controlling the Progression of Curvature in Children and Adolescent Idiopathic Scoliosis Following the Administration of Melatonin, Calcium, and Vitamin D.

Idiopathic scoliosis affects a severe number of children. Their quality of life and development are also disturbed. Some therapeutic strategies have been developed to control illness progression and to optimize the quality of life. In this perspective, randomized, case-control, interventional study, the impact of using melatonin, calcium, and vitamin D, respectively, on idiopathic scoliosis patients was analyzed. Our preliminary results showed that these drugs positively affected the illness progression quantified by the spine curvature. Patients with idiopathic scoliosis may benefit from a novel treatment by supplementation with vitamin D, calcium, and melatonin.

Quality of Life Evaluation Using SRS-30 Score for Operated Children and Adolescent Idiopathic Scoliosis.

Background and objective: Adolescent idiopathic scoliosis (A.I.S.) is a disorder with a significant impact on health and self-image. This spinal deformity can affect between 2% and 4% of the adolescent population and may alter one's quality of life. This study aims to assess the patient outcome, satisfaction, and quality of life following surgical treatment using the SRS-30 questionnaire. Materials and Methods: A number of 49 children and adolescent patients diagnosed with idiopathic scoliosis that had surgery were included in this study. They thoroughly completed the SRS-30 questionnaire before and after the surgery, based on which data analysis was carried on. Correlations between the test results and imagistic data (pre- and postoperative Cobb angle, correction rate of Cobb angle, number of instrumented spinal segments, and number of pedicle screws/laminar hooks used in the surgery) were performed. Results: Our results showed that 87.76% of the patients were girls, and the mean age at surgery was 14.83 years. Postoperatively, the Cobb angle improved significantly (p < 0.0001). The questionnaire domain "Satisfaction with management" improved dramatically after surgery, averaging 13.65 points (91% out of the maximum score). The average postoperative test score was 125.1 points. Statistically significant correlations were found between the correction rate and SRS-30 score improvement (p < 0.001), in total as well as per each domain of the survey, respectively. Comparing the questionnaire domains, "Self-image" was positively correlated with "Satisfaction with management" (p < 0.0001). Conclusions: Better correction rate led to higher values of SRS-30 score. Additionally, the younger the age at surgery is, the higher the score. The number of instrumented spinal segments does not alter the quality of life. Overall, the most crucial factor influencing patient satisfaction after surgical treatment is self-image.

Anticancer Activity of Natural and Synthetic Chalcones.

Cancer is a condition caused by many mechanisms (genetic, immune, oxidation, and inflammatory). Anticancer therapy aims to destroy or stop the growth of cancer cells. Resistance to treatment is theleading cause of the inefficiency of current standard therapies. Targeted therapies are the most effective due to the low number of side effects and low resistance. Among the small molecule natural compounds, flavonoids are of particular interest for theidentification of new anticancer agents. Chalcones are precursors to all flavonoids and have many biological activities. The anticancer activity of chalcones is due to the ability of these compounds to act on many targets. Natural chalcones, such as licochalcones, xanthohumol (XN), panduretin (PA), and loncocarpine, have been extensively studied and modulated. Modification of the basic structure of chalcones in order to obtain compounds with superior cytotoxic properties has been performed by modulating the aromatic residues, replacing aromatic residues with heterocycles, and obtaining hybrid molecules. A huge number of chalcone derivatives with residues such as diaryl ether, sulfonamide, and amine have been obtained, their presence being favorable for anticancer activity. Modification of the amino group in the structure of aminochalconesis always favorable for antitumor activity. This is why hybrid molecules of chalcones with different nitrogen hetercycles in the molecule have been obtained. From these, azoles (imidazole, oxazoles, tetrazoles, thiazoles, 1,2,3-triazoles, and 1,2,4-triazoles) are of particular importance for the identification of new anticancer agents.

Evaluating the Functional Outcomes and the Quality of Life for Pediatric Patients with Osteogenesis Imperfecta after Fracture Treatment with Intramedullary Rodding.

BACKGROUND AND OBJECTIVES: Osteogenesis imperfecta is a rare pathology involving the bones and the connective tissues, generating alterations that lead to frequent fractures during childhood. When fractures occur at birth, they are associated with an impairment of walking and the quality of life. Although surgical techniques have significantly improved in recent years, functional outcomes and the quality of life for pediatric patients that benefited from surgical management with telescopic rods have been less evaluated. This study aimed to measure functional results and determine the factors that influence the quality of life for the pediatric population diagnosed with Osteogenesis imperfecta and surgically treated using the telescopic rod approach after suffering a fracture or severe deformity. MATERIALS AND METHODS: We conducted a cohort study that consisted of 15 patients diagnosed with Osteogenesis imperfecta (average age of 11.6 years). All individuals possessed at least one intramedullary telescopic rod as a result of the surgical treatment. RESULTS: We observed that the pain, both acute and chronic, impairs the quality of life and interferes with daily living activities, for instance, self-care tasks. CONCLUSIONS: Osteogenesis imperfecta is associated with a severely damaged level of walking. All of the aspects of the pediatric patient's daily life activity seem to be affected. Furthermore, these patients, especially those residing in rural areas, have a poor quality of life.

A Prospective Cohort Study on Quality of Life among the Pediatric Population after Surgery for Recurrent Patellar Dislocation.

Patellofemoral instability is a frequent cause of knee pathology affecting quality of life among the pediatric population. Here, we present a prospective cohort study which included patients who had undergone surgical management using the lateral release and medial imbrication approach (LRMI) or medial patellofemoral ligament reconstruction (MPFL-R). The object of this study was to assess the quality of life among children that have undergone surgical treatment for patellar dislocation. Quality of life was assessed before and after surgery using the Pediatric International Knee Documentation Committee form (Pedi-IKDC), a questionnaire that aims to quantify knee functionality. Postoperative scarring was evaluated using The Stony Brook Scar Evaluation Scale. One hundred and eight patients were selected and grouped according to the type of procedure. Before surgery, the two groups had similar mean Pedi-IKDC scores (41,4 MPFL-R vs. 39,4 LRMI p = 0.314). Improvements were observed in the postoperative scores. The MPFL-R technique showed promising outcomes. When comparing the two surgical groups, there was a significant difference in favor of MPFL-R group (MPFL-R 77.71 points vs. LRMI 59.74 points, p < 0.0001-95% CI (11.22-24.72)). Using the Stony Brook Scar Evaluation Scale, a significant difference in scar quality in favor of MPFL-R was observed (4,5 MPFL-R vs. 2,77 LRMI p = 0.002). In conclusion, this study provides objective evidence-based outcome assessments that support the medial patellofemoral ligament reconstruction technique as the gold standard for patellofemoral instability.

Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents.

We report here the design, synthesis, experimental and in silico evaluation of the antibacterial and antifungal activity of some new benzo[f]quinoline derivatives. Two classes of benzo[f]quinolinium derivatives-(benzo[f]quinolinium salts (BQS) and pyrrolobenzo[f]quinolinium cycloadducts (PBQC)-were designed and obtained in two steps via a direct and facile procedure: quaternization followed by a cycloaddition reaction. The synthesized compounds were characterized by elemental and spectral analysis (FT-IR, 1H-NMR, 13C-NMR). The antimicrobial assay reveals that the BQS salts have an excellent quasi-nonselective antifungal activity against the fungus Candida albicans (some of them higher that the control drug nystatin) and very good antibacterial activity against the Gram positive bacterium Staphylococcus aureus. The PBQC compounds are inactive. Analysis of the biological data reveals interesting SAR correlations in the benzo[f]quinolinium series of compounds. The in silico studies furnished important data concerning the pharmacodynamics, pharmacokinetics and ADMET parameters of the BQS salts. Studies of the interaction of each BQS salt 3a-o with ATP synthase in the formed complex, reveal that salts 3j, 3i, and 3n have the best fit in a complex with ATP synthase. Study of the interaction of each BQS salt 3a-o with TOPO II in the formed complex reveals that salts 3j and 3n have the best-fit in complex with TOPO II. The in silico ADMET studies reveal that the BQS salts have excellent drug-like properties, including a low toxicity profile. Overall, the experimental and in silico studies indicate that compounds 3e and 3f (from the aliphatic series), respectively, and 3i, 3j and 3n (from the aromatic series), are promising leading drug candidates.

Hybrid Imidazole-Pyridine Derivatives: An Approach to Novel Anticancer DNA Intercalators.

Lack of specificity and subsequent therapeutic effectiveness of antimicrobial and antitumoral drugs is a common difficulty in therapy. The aim of this study is to investigate, both by experimental and computational methods, the antitumoral and antimicrobial properties of a series of synthesized imidazole-pyridine derivatives. Interaction with three targets was discussed: Dickerson-Drew dodecamer (PDB id 2ADU), G-quadruplex DNA string (PDB id 2F8U) and DNA strain in complex with dioxygenase (PDB id 3S5A). Docking energies were computed and represented graphically. On them, a QSAR model was developed in order to further investigate the structure-activity relationship. Results showed that synthesized compounds have antitumoral and antimicrobial properties. Computational results agreed with the experimental data.

Finding Needles in a Haystack: Determining Key Molecular Descriptors Associated with the Blood-brain Barrier Entry of Chemical Compounds Using Machine Learning.

In this paper we used two sets of calculated molecular descriptors to predict blood-brain barrier (BBB) entry of a collection of 415 chemicals. The set of 579 descriptors were calculated by Schrodinger and TopoCluj software. Polly and Triplet software were used to calculate the second set of 198 descriptors. Following this, modelling and a two-deep, repeated external validation method was used for QSAR formulation. Results show that both sets of descriptors individually and their combination give models of reasonable prediction accuracy. We also uncover the effectiveness of a variable selection approach, by showing that for one of our descriptor sets, the top 5 % predictors in terms of random forest variable importance are able to provide a better performing model than the model with all predictors. The top influential descriptors indicate important aspects of molecular structural features that govern BBB entry of chemicals.