Structure Activity Research Articles

Computational Atom-based Three-Dimensional Quantitative Structure-Activity Relationship (3D QSAR) Model for Predicting Anti-Dengue Agents

Dengue fever is a viral infection spread by the female mosquito Aedes aegypti. It is a virus spread by mosquitoes found all over the tropics with risk levels varying depending on rainfall, relative humidity, temperature and urbanization. There are no specific medications that can be used to treat the condition. The development of possible bioactive ligands to combat Dengue fever before it becomes a pandemic is a global priority. Few studies on building three-dimensional quantitative structure-activity relationship (3D QSAR) models for anti-dengue agents have been reported. Thus, we aimed at building a statistically validated atom-based 3D-QSAR model using bioactive ligands reported to possess significant anti-dengue properties. In this study, the Schrodinger PhaseTM atom-based 3D QSAR model was developed and was validated using known anti-dengue properties as ligand data. This model was also tested to see if there was a link between structural characteristics and anti-dengue activity of a series of 3-acyl-indole derivatives. The established 3D QSAR model has strong predictive capacity and is statistically significant [Model: R2 Training Set = 0.93, Q2 (R2 Test Set) = 0.72]. In addition, the pharmacophore characteristics essential for the reported anti-dengue properties were explored using combined effects contour maps (coloured contour maps: blue: positive potential and red: negative potential) of the model. In the pathway of anti-dengue drug development, the model could be included as a virtual screening method to predict novel hits.

FATTY ACID ANALYSIS FOR SEEDS OF SOME ORCHID SPECIES SPREADING IN VAN PROVINCE

Fatty acids have many important biochemical properties such as energy, metabolic and other structural activities. Orchids, which are among the common species worldwide, are used as beverages, food additives and drugs in societies. Orchid seeds are one of the smallest seeds that do not contain nutrient tissue naturally and are rich in fatty acids. Plants dried at room temperature were extracted using chloroform/methanol (2:1). Their methyl esters were analyzed using a Gas Chromatography device. As a result of the analysis, a total of 16 fatty acids were determined. Out of these, palmitic acid (16:0), oleic acid (18:1n-9) and linoleic acid (18:2n-6) were found as major fatty acids. Other fatty acids, myristic, pentadecanoic, stearic, linolenic, arachidonic and docosapentaenoic acid were detected in trace amounts. When the percentage distribution of palmitic acid was considered, it was observed that it ranged between 16.76% and 25.32%, and the highest one was in Anacamptis collina. It was also found that the distribution of stearic acid was similar among species. Oleic acid exhibited the highest distribution as percentage in Orchis simia (27.33%), Orchis mascula subsp. pinetorum (25.16%) and Orchis spitzelii (25.66%). Linoleic acid showed different distribution among species. The lowest percentage was found in Orchis tridentata (15.13%), while the highest one was in Orchis mascula subsp. pinetorum (34.02%). This study carried out on fatty acids is a part of the study on the use of natural bioactive products and fatty acids, hoping to be used in industrial applications.

Erratum: Yaragani et al. Structural, Magnetic and Gas Sensing Activity of Pure and Cr Doped In2O3 Thin Films Grown by Pulsed Laser Deposition. Coatings 2021, 11, 588

The authors wish to make the following changes to their published paper [...]

Polymorphism control of active pharmaceutical ingredients

Рolymorphism is receiving increasing attention due to its influence on the physicochemical and pharmacological properties of the active pharmaceutical ingredients (API) while maintaining the molecular structure. This review is devoted to the problem of APIs phase state control both at the development stage and during the circulation of the drug. The term «polymorphism» has different definitions depending on the branch of science. There is no unambiguous solution to this issue in the regulatory documentation of pharmaceutical industry either. Based on the analysis of literary sources, the article presents a comparison of pharmacopeia methods, recommended in Russian and foreign regulatory documents for the analysis of polymorphism of medicinal substances, including state pharmacopeias of Russia, Belarus, Kazakhstan, the USA, and Japan, as well as international pharmacopeias of the European Economic Union and the Eurasian Economic Union. The trend on using a complex of high-tech equipment is revealed. A systematic approach to analysis based on X-ray diffraction, thermal, spectral, microscopic, biological, and physical methods for determining constants makes it possible not only to identify the polymorphic modification of API, but also to characterize its structure, morphology, physicochemical properties and pharmacological activity. In the Russian Federation, the phenomenon of polymorphism is being studied especially intensively, and some control methods, such as biological methods, are validated only in Russian pharmacopeia. A promising direction for further research is the improvement and harmonization of regulatory documentation within the framework of this chemical and technological field of pharmacy. A global approach will help to reduce not only the probability of poor-quality products entering the market, but also the costs of establishing the authenticity of the active pharmaceutical ingredient produced.

Formation of the penitentiary System of Soviet Ukraine (first half of the 20th century)

The process of organizing and becoming a system of execution of criminal penalties in Soviet Ukraine has been investigated since the Education of the Ukrainian SSR until 1930 - the beginning of the 1950s.; marked the main stages of the development of the state; The main regulatory acts of the structural and organizational activities of the penitentiary system are analyzed. In the 1920s. The Soviet penitentiary system was considered as a composite punitive system of the state and an effective means of combating the «class enemy». At the same time, the system of correctional institutions in Ukraine has not yet been considered as a means of severe punishment in the conditions of isolation from society, and it was also interpreted as an integral part of the condemnation system of convicts in social waste. The system of execution of criminal penalties to which correctional labor camps and general places of detention were determined. Independent subsystems were considered prison institutions (ordinary and investigative prisons), as well as labor colonies for minors and children's educational colonies. It has been established that under the conditions of Stalinism, an extensive network of the criminal executive system was a kind of foundation of totalitarian regime, was in an organic relationship with the administrative command system. The state administration of criminal and executive institutions in the post-war years carried out, and based on the principles of strict control of various departments of the NKVD, NKGB, MJ, Ministry of Internal Affairs.

Synthesis, Structure, DFT, and Biological Activity of Metal Complexes of Norfloxacin and Metformin Mixed Ligand

Synthesis, Structure, DFT, and Biological Activity of Metal Complexes of Norfloxacin and Metformin Mixed Ligand

A DETAILED CADAVERIC STUDY ON GUDA MARMA WITH RESPECT TO ITS SURGICAL ANATOMY THROUGH DISSECTION

Ayurveda is an ancient science which deals with theoretical and practical knowledge with help of cadaver, structural and functional activity. In various Ayurvedic textbooks mention Marma (vital points of the body) which is a vital part of the body. Ayurveda is an ancient science which deals with theoretical and practical knowledge with help of cadaver, structural and functional activity. The detailed knowledge of Marma (vital points of the body) is important from the surgical point of view surgical procedures like Agnikarma (thermal cauterization), Ksharakarma (therapeutic application of caustic material), Raktamokshana (bloodletting), etc. are used as a part of the surgery. The aim of this study is to reconstruct the concept of Guda Marma in the light of current knowledge and studied the applied aspect of Guda Marma. Cadaveric study was done in 5 human cadavers to visualize all the structures (muscles, artery, vein, nerve, etc.) of Guda (Anus) Pradesh (Anorectal region) in terms of Ayurvedic sciences and Modern Medical Sciences. The exact location, reginal anatomy as well as applied aspect of Guda Marma in terms of surgery were analyzed and correlated with modern sciences. Guda (Anus) is the seat of Prana (the breath of life) and it has regarded as one of the ten Prana (the breath of life) yatan. Guda Marma is one among the Mamsa Marma (vital points of the body) and categorized under Sadhya Prana (the breath of life) hara Marma (vital points of the body). The importance of this region can be assessed by the fact that two of the diseases of Guda (Anus) (Arsha and Bhagandara) have been considered as Mahagada. Guda Marma is the vital organ or site of the human body having a rich blood supply which correct knowledge and applied aspects concerning anorectal injuries and disorders is essential.

The Brain Structure and Intrinsic Characters of Falsification Thinking in Conditional Proposition Testing.

Wason's selection task (WST) as a representative of the field of conditional proposition testing has been explored by multiple disciplines for more than 50 years, but the neural basis of its key falsification thinking remains unclear. Considering that the accuracy of individuals in WST has stability over time, we believe that falsification thinking has a specific brain structural basis and intrinsic neural characteristics. To test this hypothesis, we studied individuals who were able to complete the WST using T1-weighted MRI (using voxel-based morphology (VBM) analysis) and resting electroencephalogram (EEG) (using microstate analysis, which can reflect stable cognitive characteristics of individuals) techniques. First, VBM analysis found that, compared with the verification group, the gray matter volume (GMV) of the left inferior temporal gyrus and the right superior temporal region of the falsification group was larger, whereas the GMV in the cerebellum of the verification group was significantly larger than that of the falsification group. Subsequently, the results of the microstate analysis of the resting EEG data showed that the contribution of class A of the falsification group, which is closely related to the language network, is significantly higher than that of the verification group. Our structural MRI and resting EEG results consistently show that the structure and intrinsic activity pattern of the temporal lobe in individuals with falsification thinking are specific. Furthermore, the findings may provide potential insights into the role of the temporal lobe (which is also a brain region of language processing) in thought.

Synthesis, crystal structure and catalytic activity of a new organic–inorganic hybrid cobalt phosphite

Synthesis, crystal structure and catalytic activity of a new organic–inorganic hybrid cobalt phosphite

Effects of Adsorbing Noble Metal Single Atoms on the Electronic Structure and Photocatalytic Activity of Ta3N5

Effects of Adsorbing Noble Metal Single Atoms on the Electronic Structure and Photocatalytic Activity of Ta₃N₅

Piperidinium surfactant effect of structure and functional activity

Piperidinium surfactant effect of structure and functional activity

Tradition of raw milk consumption and its health impact among people living in the coastal regions of Bangladesh

Milk is a nutrient-rich liquid food for human and animals. However, owing to its complex biochemical structure and high water activity, it serves as an outstanding microorganism growth medium under suitable conditions. People in Bangladesh's coastal areas have a lifestyle and tradition that includes drinking raw milk for nutrition or as an energy drink, which presents a health risk to them. The present cross-sectional study was carried out to determine the reasons for drinking raw milk in coastal areas, as well as the public health impact of doing so. A total of 100 respondents were interviewed and subsequently, milk samples were collected for quality testing through methylene blue reduction test (MBRT). Among 100 respondent 70 were consumers and 30 were farmers. Results showed that the samples of farmers were better than that of consumers. The majority of raw milk consumers were male who thought raw milk was more nutritious than heat-treated milk. Furthermore, the majority of them were professionally engaged in farming. Both consumers and farmers had less educational qualifications, managed their cattle in dirty environments, practiced extensive grazing system on communal grazing areas and around one fourth of them vaccinated their animals. Furthermore, the findings revealed that 40% of respondents were between the ages of 35 and 45, with 62% reporting no health complications as a result of drinking raw milk and the remainder reporting mainly gastrointestinal problems. According to the findings of this report, the quality of raw cow milk was poor; unhygienic practices and poor animal husbandry at farm level predisposed farmers, consumers and the public to risk of contracting milk-borne infections and associated bacterial resistances. It is recommended that veterinarians, extension officers and all stakeholders should play their roles in ensuring safe quality milk supply to consumers.
 Asian Australas. J. Biosci. Biotechnol. 2021, 6 (1), 10-18

Screening of the HBx transactivation domain interacting proteins and the function of interactor Pin1 in HBV replication

Hepatitis B virus (HBV) X protein (HBx) has been determined to play a crucial role in the replication and transcription of HBV, and its biological functions mainly depend on the interaction with other host proteins. This study aims at screening the proteins that bind to the key functional domain of HBx by integrated proteomics. Proteins that specifically bind to the transactivation domain of HBx were selected by comparing interactors of full-length HBx and HBx-D5 truncation determined by glutathione-S-transferase (GST) pull-down assay combined with mass spectrometry (MS). The function of HBx interactor Pin1 in HBV replication was further investigated by in vitro experiments. In this study, a total of 189 proteins were identified from HepG2 cells that specifically bind to the transactivation domain of HBx by GST pull-down and subsequent MS. After gene ontology (GO) analysis, Pin1 was selected as the protein with the highest score in the largest cluster functioning in protein binding, and also classified into the cluster of proteins with the function of structural molecule activity, which is of great potential to be involved in HBV life cycle. The interaction between Pin1 and HBx has been further confirmed by Ni2+-NTA pulldown assay, co-immunoprecipitation, and immunofluorescence microscopy. HBsAg and HBeAg levels significantly decreased in Pin1 expression inhibited HepG2.2.15 cells. Besides, the inhibition of Pin1 expression in HepG2 cells impeded the restored replication of HBx-deficient HBV repaired by ectopic HBx expression. In conclusion, our study identified Pin1 as an interactor binds to the transactivation domain of HBx, and suggested the potential association between Pin1 and the function of HBx in HBV replication.

Co(II) coordination polymer: crystal structure and treatment activity against chronic obstructive pulmonary disease

By employment of a semi-flexible quadritopic N-donor ligand, 5,5′-bipyrimidine (bpym), a new azide-based coordination polymer (CP) with the chemical formula of {[Co3(bpym)3(N3)6]·2H2O} n has been successfully prepared. Its application values on the chronic obstructive pulmonary disease (COPD) were assessed and the specific mechanism was explored as well. The levels of the inflammatory cytokines released by the COPD animal was measured with enzyme linked immunosorbent assay (ELISA) detection assay. The activation level of the Nuclear factor kappa beta (NF-κB) signaling pathway in the lung epithelial cells was determined with real time Reverse Transcription Polymerase Chain Reaction (RT-PCR) assay. Above all, the compound exhibited excellent treatment activity on COPD. The Co complex was found to form multiple binding interactions within the docking pocket, all those binding interactions were formed by the pyrimidine rings. Above all, the compound has excellent application values on the COPD treatment.

Abstract 83: Structural and biochemical properties of DIRAS3 N-terminal extension that permit its function as a tumor suppressor of oncogenic K-RAS

Abstract DIRAS3 is an imprinted tumor suppressor gene that encodes a small GTPase of the RAS superfamily. In contrast to oncogenic RAS proteins, DIRAS3 inhibits tumor growth and migration, while inducing autophagy and tumor dormancy. DIRAS3 inhibits PI3K/AKT/mTOR and RAS/MAP signaling. DIRAS3 inhibits oncogenic, mutant K-RAS signaling by binding directly to mutant K-RAS and disrupting K-RAS dimers and clusters on the inner leaflet of the plasma membrane. DIRAS3 bears 60% amino acid homology to K-RAS, differing by the addition of a distinctive 34 amino acid N-terminal extension (NTE). Both the NTE and an intact C-terminal CAAX box are required for the suppressor function of DIRAS3 in breast and ovarian cancers. While prenylation of the CAAX box is thought to facilitate binding of DIRAS3 to the inner leaflet of the cell surface membrane through a lipid tail, how the NTE influences membrane association is not well understood. In this study, we apply biochemical and biophysical methods to investigate NTE structure and ligand binding activities using synthetic wild type and mutated NTE peptides. Using a lipid overlay assay and surface plasmon resonance (SPR) analysis, we found that the DIRAS3 NTE has affinity for phosphatidylinositol phosphate lipids, especially PI(3,4,5)P3 and PI(4,5)P2. SPR demonstrated a strong interaction between NTE and PIP3 (dissociation constant of ~36 nM) with a cooperative self-association of NTE on the PIP3 sensor surface. Isothermal titration calorimetry revealed that NTE-PIP3 binding is complex, involving multiple sites and cooperativity, that appeared dominated by entropic interaction. Structural analysis of NTE mutants with circular dichroism spectroscopy indicated that the NTE is mainly unstructured in solution, however PIP3-binding induces a conformational rearrangement of the NTE that involves a hydrophobic surface of an amphipathic helix region. Furthermore, mass spectrometry identified N-myrisoylation of glycine in the NTE region of DIRAS3, which is unique among RAS family proteins. In addition, SPR screening of a K-RAS peptide library and kinetic analysis of the interaction between DIRAS3 NTE and K-RAS revealed engagement of the NTE with the effector lobe of K-RAS and a conformational change in the NTE•K-RAS complex. Together, our study suggests that DIRAS3 NTE may play an important role in inhibiting K-RAS and AKT signaling by facilitating specific protein-lipid interactions at the plasma membrane. The affinity of the NTE for PIP3 could contribute to the known regulation of PI3K by DIRAS3. Moreover, functional DIRAS3 may be tethered to the inner leaflet of the cell membrane at two points, by prenylation of the CAAX box at the C-terminal and by myristoylation of the NTE. Citation Format: Xiaowen Liang, Kwangkook Lee, Sung Y. Jung, Gamze Bildik, Weiqun Mao, Joshua P. Gray, Steven W. Millward, Zhen Lu, Robert C. Bast. Structural and biochemical properties of DIRAS3 N-terminal extension that permit its function as a tumor suppressor of oncogenic K-RAS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 83.

Biomolecular changes and subsequent time-dependent recovery in hippocampal tissue after experimental mild traumatic brain injury

Traumatic brain injury (TBI) is the main cause of disability and mortality in individuals under the age of 45 years. Elucidation of the molecular and structural alterations in brain tissue due to TBI is crucial to understand secondary and long-term effects after traumatic brain injury, and to develop and apply the correct therapies. In the current study, the molecular effects of TBI were investigated in rat brain at 24 h and 1 month after the injury to determine acute and chronic effects, respectively by Fourier transform infrared imaging. This study reports the time-dependent contextual and structural effects of TBI on hippocampal brain tissue. A mild form of TBI was induced in 11-week old male Sprague Dawley rats by weight drop. Band area and intensity ratios, band frequency and bandwidth values of specific spectral bands showed that TBI causes significant structural and contextual global changes including decrease in carbonyl content, unsaturated lipid content, lipid acyl chain length, membrane lipid order, total protein content, lipid/protein ratio, besides increase in membrane fluidity with an altered protein secondary structure and metabolic activity in hippocampus 24 h after injury. However, improvement and/or recovery effects in these parameters were observed at one month after TBI.

A Right to Have One’s Case Heard within a Reasonable Time before the Czech and the Polish Supreme Administrative Courts – Standards, the Reality and Proposals for the Future

The right to have one’s case heard within reasonable time constitutes one component of an effective judicial protection. The aim of this paper is to establish the reasons for delays in proceedings before the Supreme Administrative Courts in the Czech Republic and in Poland, to analyze why they exist, and to formulate proposals on how the structural and procedural activity of these courts could be organized more effectively. The international and national standards as well as the Polish and the Czech standards pertaining to the right to have one’s case heard within reasonable time and the reasons for unjustified delays will be examined, and the explanations for their occurrence will be provided. Proposals will then be formulated on how to make the procedures more effective. The ideas formulated are relevant in both countries for the two judicial systems, but also for other judiciaries, which also experience the same problems with system delays.

Evaluating bacterial contamination of free bone fragments falling to the ground and the effectiveness of antiseptic solutions.

This study aims to determine the contamination incidence rate of bone fragments that have been dropped on the floor of the operating theatre, as well as how effective antimicrobial solutions are at decontaminating them. Bone fragments obtained after 30 total knee arthroplasties were used in the study. Inert pieces of bone emerging after the bone cuts during total knee arthroplasty were divided into 1 × 1cm fragments. The bone fragments were first left in free fall on the floor of the operating theatre and then were kept in a number of antimicrobial solutions for 15s. Subsequently, they were microbiologically and histopathologically examined. A swab culture was also taken from the floor of the operating theatre. It was determined that 63.3% of osteochondral fragments in the non-intervened group were contaminated. Growth was likewise detected in all swab cultures. Microorganisms growing in the swab culture and the non-intervened group were similar and mostly Staphylococcus epidermidis and Klebsiella pneumoniae. When the growth rates of the 10% povidone-iodine and 4% chlorhexidine gluconate groups were compared with the growth rate of the non-intervened group, a statistical difference was found. No difference was determined between the growth rates of the sodium hypochlorite and the non-intervened groups. The histopathological analysis revealed no statistical difference between the groups in terms of bone marrow, vascular structure, fat tissue, and osteoblastic activity results in the osteochondral fragments CONCLUSION: Bone tissues dropped from a sterile area on the floor of the operating theatre are highly contaminated. An effective decontamination without bone cell toxicity was achieved using povidone-iodine. Although chlorhexidine gluconate solution had an effective decontamination effect compared to the non-intervened group, it was not 100% effective. Sodium hypochlorite solution was not effective in the decontamination of grafts under our working conditions.

Integrated Three-Dimensional Carbon Nanopolyhedron/Metal Sulfides: An Efficient Electrocatalyst Toward Oxygen Reduction Reaction

Carbon-based materials hybridized with metal sulfides have gained growing attention as catalytic materials for oxygen reduction reaction (ORR) due to their synergistic effects in terms of richer structural features and higher electrochemical activities. Here, a series of Zn/Co/Fe-based metal-organic frameworks (MOFs) as the precursors, which can be adopted as efficient ORR catalysts, were synthesized through a sulfuration–calcination treatment. The effects of precursor composition, heteroatom doping, and pyrolysis temperature on the structure and electrochemical performance of the catalysts were discussed in detail. It is found that well-grown carbon nanotubes (CNTs) on the surface of graphitic carbon matrix are formed under the synergy effect of trimetallic-based species during pyrolysis. Benefiting from the three-dimensional unique structure with appropriate dopants and high porosity, the catalyst derived from the optimized Zn/Co/Fe-MOFs achieves a half-wave potential of 0.87 V in an alkaline medium for ORR, which is comparable with commercial electrocatalysts. In addition, an outstanding ORR durability of the proposed catalyst in alkaline media was also demonstrated. This work highlights the potential to rationally design and fabricate high-performance ORR catalysts for commercialization.

Structural Analysis, Antifungal Activity and Molecular Docking Study of a Compound Isolated from Streptomyces species

Background: The emergence of drug resistance is the biggest threat; consequently, novel antimicrobial agents from natural sources is the need of the hour. This study was designed to isolate and evaluate a bioactive compound from actinomycete against human pathogens. Methods: In search of a new antimicrobial compound with enhanced potency, several actinomycetes were isolated and screened for their anidermatophytic acitivity. The bioactive compound was extracted and purified by chromatographic technique. The structure of the extracted bio active compound was elucidated by mass and NMR data. The synthesized bioactive compound was further tested for its antidermatophytic activity by the micro broth dilution method. Results: Streptomyces ARITM 03 was isolated that exhibited antifungal activity against human pathogenic fungi by primary and secondary screening methods. The MIC of bioactive compound was found to be 1250, 312.5 and 2500 μg/ml against tested fungal pathogens A. niger, C. albicans and M. canis, respectively. Chromatography analysis of active metabolite showed a single spot having Rf value of 0.74 and FT-IR spectrum displaying the presence of OH, CO=NH2 functional amide group, and C=O keto groups in the structure. The mass and NMR spectra revealed the molecular formula C26H44N4O6 of bioactive compound. The azole derivative showed an acceptable docking score and exhibited a greater zone of inhibition in comparison to the other compounds. Conclusion: The results presented in this paper provided an insight into the capability of Streptomyces sp. ARITM03 as a potential source of bioactive secondary metabolites compound a molecule to develop other azoles, to be used clinically to overcome adverse effects like gynecomastia and hepatotoxicity due to extensive use of current azole antifungal agents.