Prediction Of Activity Spectra For Substances Research Articles

IN SILICO PREDICTION OF POTENTIAL DERMATOLOGICAL EFFECTS OF A SYNTHETIC ANTIOXIDANT

Nowadays, in silico prediction has become standard in the development of new drugs. Computer screening of known drugs provides an efficient approach to repurposing these agents for new indications. This sparked our interest in conducting an in silico analysis of ethylmethylhydroxypyridine succinate (EMHPS) for pharmacological effects potentially useful in dermatology. The aim of this study is to perform an in silico search for the effects of the synthetic antioxidant EMHPS that are potentially useful for the treatment of skin diseases. Retrospective computer prediction of the EMGPS structure was performed using the Drug2ways methodical approach and the PASS (Prediction of Activity Spectra for Substances) program online. The EMHPS molecule consists of two active fragments, which were analyzed separately. In the structure of 2-ethyl-6-methyl-3-hydroxypyridine, 125 types of activity were predicted, while in succinate - 734 types of activity. From the array of prognostic data, effects that may be relevant for the treatment of skin diseases were extracted. These include anti-seborrheic, anti-alopecia, anti-eczema, anti-pruritic, and anti-infectious effects, as well as photosensitizing action and lack of skin irritation. According to the forecast, these effects may be due to the influence of the components of the EMHPS molecule on membranes, antioxidant protection, the state of connective tissue, enzymes, and signaling pathways involved in the development of inflammation, as well as on the pathogenicity factors of microorganisms. Therefore, in silico screening of new types of activity in EMHPS allowed us to predict some effects useful in the treatment of dermatological pathology. Undoubtedly, the results of the forecast must be verified by practice, but they allow us to create a working hypothesis and approach the planning of experiments more rationally, which corresponds to modern trends in pharmacology.

Modeling of Effectiveness of N3-Substituted Amidrazone Derivatives as Potential Agents against Gram-Positive Bacteria

Prediction of the antibacterial activity of new chemical compounds is an important task, due to the growing problem of bacterial drug resistance. Generalized linear models (GLMs) were created using 85 amidrazone derivatives based on the results of antimicrobial activity tests, determined as the minimum inhibitory concentration (MIC) against Gram-positive bacteria: Staphylococcus aureus, Enterococcus faecalis, Micrococcus luteus, Nocardia corallina, and Mycobacterium smegmatis. For the analysis of compounds characterized by experimentally measured MIC values, we included physicochemical properties (e.g., molecular weight, number of hydrogen donors and acceptors, topological polar surface area, compound percentages of carbon, nitrogen, and oxygen, melting points, and lipophilicity) as potential predictors. The presence of R1 and R2 substituents, as well as interactions between melting temperature and R1 or R2 substituents, were also considered. The set of potential predictors also included possible biological effects (e.g., antibacterial, antituberculotic) of tested compounds calculated with the PASS (Prediction of Activity Spectra for Substances) program. Using GLMs with least absolute shrinkage and selection (LASSO), least-angle regression, and stepwise selection, statistically significant models with the optimal value of the adjusted determination coefficient and of seven fit criteria were chosen, e.g., Akaike’s information criterion. The most often selected variables were as follows: molecular weight, PASS_antieczematic, PASS_anti-inflam, squared melting temperature, PASS_antitumor, and experimental lipophilicity. Additionally, relevant to the bacterial strain, the interactions between melting temperature and R1 or R2 substituents were selected, indicating that the relationship between MIC and melting temperature depends on the type of R1 or R2 substituent.

Quasi-Podands with 1,2,3-Triazole Rings from Bile Acid Derivatives: Synthesis, and Spectroscopic and Theoretical Studies.

An innovative approach to producing derivatives of bile acids has been devised, utilizing the principles of "click" chemistry. By employing intermolecular [3 + 2] cycloaddition between the newly developed acyl propiolic esters of bile acids and the azide groups of 1,3,5-tris(azidomethyl)benzene, a novel class of quasi-podands featuring 1,2,3-triazole rings has been synthesized. Identifying and characterizing these six compounds involved comprehensive analysis through spectral techniques (1H NMR, 13C NMR, and FT-IR), mass spectrometry, and the PM5 semiempirical method. The synthesized compounds' pharmacotherapeutic potential has been evaluated, employing the Prediction of Activity Spectra for Substances (PASS) methodology. Additionally, molecular docking was performed for all molecules.

In vitro antimicrobial, anticancer evaluation, and in silico studies of mannopyranoside analogs against bacterial and fungal proteins: Acylation leads to improved antimicrobial activity

Carbohydrate analogs are an important, well-established class of clinically useful medicinal agents that exhibit potent antimicrobial activity. Thus, we explored the various therapeutic potential of methyl α-D-mannopyranoside (MαDM) analogs, including their ability to synthesize and assess their antibacterial, antifungal, and anticancer properties; additionally, molecular docking, molecular dynamics simulation, and ADMET analysis were performed. The structure of the synthesized MαDM analogs was ascertained by spectroscopic techniques and physicochemical and elemental analysis. In vitro antimicrobial activity was assessed and revealed significant inhibitory effects, particularly against gram-negative bacteria along with the prediction of activity spectra for substances (PASS). Concurrently, MαDM analogs showed good results against antifungal pathogens and exhibited promising anticancer effects in vitro, demonstrating dose-dependent cytotoxicity against Ehrlich ascites carcinoma (EAC) cancer cells while sparing normal cells from compound 5, with an IC50 of 4511.65 µg/mL according to the MTT colorimetric assay. A structure–activity relationship (SAR) study revealed that hexose combined with the acyl chains of decanoyl (C-10) and benzenesulfonyl (C6H5SO2-) had synergistic effects on the bacteria and fungi that were examined. Molecular docking was performed against the Escherichia coli (6KZV) and Candida albicans (1EAG) proteins to acquire insights into the molecular interactions underlying the observed biological activities. The docking results were further supported by 100 ns molecular dynamics simulations, which provided a dynamic view of the stability and flexibility of complexes involving MαDM and its targets. In addition, ADMET analysis was used to evaluate the toxicological and pharmacokinetic profiles. Owing to their promising drug-like properties, these MαDM analogs exhibit potential as prospective therapeutic candidates for future development.

Synthesis, crystal structure, DFT calculations, NBO, Fukui function, NCI-RDG, Hirshfeld surface analysis, NLO properties and molecular docking analysis on (E)-N'-(3-methoxybenzylidene)-2-(quinolin-8-yloxy) acetohydrazide

In this study, we present the synthesis and characterization of a novel organic compound, (E)-N'-(3-methoxybenzylidene)-2-(quinolin-8-yloxy) acetohydrazide. Our characterization includes single crystal X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and UV–visible spectroscopy. We also conducted Hirshfeld surface (HS) analysis to investigate intermolecular interactions. The compound crystallizes in the triclinic system with space group P−1. We employed density functional theory (DFT) with the B3LYP function and the 6–311 G (d, p) basis set to calculate its electronic properties. Additionally, we explored its nonlinear optical (NLO) behavior, determining the electric dipole moment (μ), polarizability (α), and hyperpolarizability (β), second-order hyperpolarizabilities (γ) using the same basis set. To evaluate the NLO properties of MBQA, we conducted frontier molecular orbitals (FMO) analysis, examined HOMO-LUMO energies, determined the energy band gap, studied the density of states (DOS), and assessed global chemical reactivity descriptors. We also performed a molecular electrostatic potential (MEP) simulation to identify optimal sites for both electrophilic and nucleophilic attacks. Our analysis further included a reduced density gradient (RDG) analysis to investigate various types of intermolecular interactions in MBQA, such as repulsive, attractive, and Van der Waals interactions while also distinguishing between strong and weak interactions. To understand the molecular stability and interactions, we conducted natural bond orbital (NBO) analysis, which provided insights into hyperconjugative interactions, charge delocalization and electron density ED among the molecular components. Finally, we assessed the biological activity of the MBQA molecule by predicting its potential pharmacological activities using the prediction of activity spectra for substances (PASS) and conducting molecular docking analyses. This comprehensive study provides valuable insights into the structural, electronic, and biological properties of (E)-N'-(3-methoxybenzylidene)-2-(quinolin-8-yloxy) acetohydrazide (MBQA).

Exploratory Studies on Chrysin via Antioxidant, Antimicrobial, ADMET, PASS and Molecular Docking evaluations

IntroductionChrysin, a flavonoid found in Feng Jiao (Chinese name for propolis), exhibits a wide array of pharmacological activities and is recognized for the significant roles it plays in traditional Chinese medicine. The present study aimed to explore the in vitro antioxidant and antimicrobial potentials of chrysin and provide mechanistic insights via in silico experiments. MethodsThe in vitro antioxidant and antimicrobial activities of chrysin, a natural flavone found in propolis was investigated. Molecular docking interactions, the Adsorption, Distribution, Metabolism, Elimination and Toxicity (ADMET) and Prediction of Activity Spectra for Substances (PASS) were used to predict the biological activities of chrysin. ResultsChrysin exhibited a considerable 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals scavenging activity and ferric reducing antioxidant capacity. Chrysin demonstrated inhibition against S. typhi, and B. subtilis with lowest MIC value of 1.25 mg/mL which was similar to that of chloramphenicol. Drug-likeness and ADMET study of the two compounds showed their physicochemical properties as non-toxic, non-mutagenic, high permeability, good solubility and absorption characteristics. DiscussionThe research below shows that chrysin and silymarin had antioxidant, free radical scavenging, antibacterial, hepatoprotective and anticarcinogenic properties based on PASS prediction of biological activities. Molecular docking of chrysin and silymarin, a standard hepatoprotective drug, with tumour necrosis factor alpha converting enzyme (TACE) and manganese-dependent superoxide dismutase (SOD 2) showed interactions with LEU 401, VAL 402, HIS 405 amino acid residues at the active sites of TACE. Chrysin non-covalently interacted with amino acids of SOD 2 at the active site while silymarin non-covalently interacted at a site different from the active site. Silymarin demonstrated a minimum binding energy of – 9.7 Kcal/mol and – 7.0 Kcal/mol for TACE and SOD 2, respectively while chrysin showed a minimal binding energy of – 9.0 Kcal/mol and – 6.8 Kcal/mol for TACE and SOD2 respectively. ConclusionThe study concluded that chrysin exhibited antioxidant and antimicrobial activity via inhibition and regulation of TACE and SOD2 and possibly offer protection against hepatotoxicity in animal experimental models.

Synthesis, spectroscopic analysis, and computational-based investigations on ‘azo-coumarin-Co(II)-galangin’ hybrids exhibit multipotential activities

The present study synthesized a series of cobalt (II) metal ion frame hybrid candidates (6a–6f) bearing phyto-flavonol galangin with substituted aryl diazenyl coumarins, and further structural confirmation was validated by various spectral techniques, including NMR, ATR-FTIR, UV-vis, HPLC, XRD, etc. Therapeutic potency was investigated via PASS (prediction of activity spectra for substances), molecular docking, molecular dynamics simulation, prediction of toxicity, pharmacokinetics, and drug-likeness scores, along with the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), with their energy gaps (ΔEH–L) to locate the most potential therapeutic candidates. The PASS prediction (Pa > Pi score) showed that proposed metal complexes have kinase inhibitors, antioxidative, and antischistosomal activities with potential molecular docking scores (> −7 kcal/mol) against selected targeted enzymes. Further, the MD-simulation (RMSD, RMSF, Rg, and H-bonds) of the most potential docking complex, ‘HER2-6d’, showed a minimum deviation similar to the standard drug (lapatinib) at 100 ns, indicating that 6d could be a potential noncovalent anticancer inhibitor. In addition, metal complexes possess a non-toxic and ideal drug-ability profiles, and positive electron space in an excited state increases the binding affinity towards target enzymes. Among all six ligands, 6c and 6d were the two most multipotent therapeutic agents from the above analyses. In summary, this could be a feasible approach towards the utilization of phytochemicals in mainstream therapeutic applications, where bioinformatics tools help to select a lead drug candidate at an early stage and guide for higher experimental success by proceeding with potential candidates. Communicated by Ramaswamy H. Sarma

Survey of Medicinal and Invasive Weeds in Paddy Field – Phytochemical and GC-MS Profiling of Cyanotis axillaris R. & S.

This study aims to determine the dominant weed species associated with rice crop fields in the Eppodhumvendran region of Thoothukudi district, Tamil Nadu and to analyze the phytochemicals, identify the bioactive compounds in ethanol extract using gas chromatography–mass spectrometry (GC-MS) and find their bioactivity using prediction of activity spectra for substances (PASS) prediction in Cyanotis axillaris. The documentation of medicinal weeds was carried out with the help of traditional local healers in Eppodhumvendran region. Phytochemical screening and GC-MS analysis of C. axillaris were performed to evaluate the chemical profiling of the extract. A total of 25 plant species regarded as invasive species/weeds were identified with the help of traditional local healers. The most commonly mentioned plant family was the Poaceae with a total of five species followed by the Euphorbiaceae, Asteraceae and Commelinaceae. Among these, C. axillaris is being studied for its potentiality due to its strong therapeutic value. The aerial plant part contains phytoconstituents such as alkaloids, glycosides, quinones, phenolics, steroids and terpenoids. The GC-MS results revealed 30 bioactive compounds, which were predicted using the PASS prediction method. The study highlights the importance of weeds in the paddy field ecosystem. The results reveal that C. axillaris contains various phytocomponents and that more research into their phytopharmaceutical relevance is required in the future.

Antifungal potential of mannopyranoside derivatives through computational and molecular docking studies against Candida albicans 1IYL and 1AI9 proteins

Methyl α-D-mannopyranoside (MAM) is a naturally occurring carbohydrate derivative that has gained attention in drug discovery due to its potential therapeutic applications, particularly as an antifungal agent. In this study, we employed a computational approach to investigate the interactions between MAM and two Candida albicans antifungal proteins, 1IYL and 1AI9, through molecular docking simulations. Furthermore, we performed a PASS (Prediction of Activity Spectra for Substances) analysis to predict MAM potential biological activities, explored the pharmacokinetic properties and ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles, and optimized the MAM using the density functional theory (DFT) method. The molecular docking results revealed favorable binding interactions between MAM and the active sites of the 1IYL and 1AI9 proteins, suggesting potential antifungal activity. Additionally, the ADMET profiles indicated low toxicity and suitable drug-like properties, such as moderate metabolic stability and minimal risk of adverse effects. Furthermore, DFT optimization was performed to investigate the molecular geometry and electronic properties of MAM. The optimization results provided valuable information on the stability and reactivity of MAM, enabling a better understanding of its chemical behavior and potential modifications for enhanced activity. Finally, PASS prediction was employed to evaluate MAM's potential biological activities beyond its antifungal properties. The analysis revealed several potential activities, including antibacterial, antiviral, and immunomodulatory effects, expanding the scope for future research and therapeutic applications. In conclusion, this computational study sheds light on the molecular interactions, pharmacokinetic properties, ADMET profiles, DFT optimization, and PASSES predictions of MAM. These findings highlight the potential of MAM as a promising antifungal agent with favorable pharmacological properties.

Biological activity spectra of the main phytochemicals of Silybum marianum L. Gaertn. by in silico study

The main objective of bioinformatics is to augment the perception of biological data. Bioinformatics gains information from computer analysis of biological practices. Biologically active principles have both pharmaceutical and adverse effects on the organisms. PASS (Prediction of Activity Spectra for Substances) software is used to estimate the general efficacy and safety of the phytochemicals. PASS simultaneously predicts several hundreds of biological activities of natural and synthetic chemical compounds. The average precision of prediction is about 90%. The extract from the seed of Silybum marianum contains silymarin, which is a complex mixture of polyphenolic molecules, including seven closely related flavonolignans, namely, silybin A, silybin B, isosilybin A, isosilybin B, silychristin, isosilychristin, silydianin and one flavonoid namely taxifolin. Silymarin has been used to treat various hepatic diseases, including chronic and acute liver diseases in canines and felines. It is used as a nutritional supplement to treat liver diseases and toxicities and prevent certain cancers in companion animals. In the present study, the main phytochemicals reported from Silybum marianum L. Gaertn. were subjected to in-silico evaluation using PASS software. The methods, biological activity spectra and significance of the in-silico study are discussed. Keywords: Efficacy, In Silico, PASS, Phytochemicals, Silybum marianum, Toxicity

In-silico PASS prediction for medicinal potency of antioxidant from Ranunculus japonicus Thunb.

Ranunculus japonicus has been traditionally used to treat various ailments, including malaria, jaundice, gastric problems, toothache, and eye inflammation. Recent studies reported that the plant extract effectively treat rheumatoid arthritis due to its secondary metabolites with antioxidant activities, such as flavonoids and phenols. In this study, we analyzed the flavonoids and phenols from R. japonicus using in silico methods. The study determined the flavonoid and phenol contents based on existing literature. The antioxidant potential analysis was conducted using PASS (Prediction of Activity Spectra for Substances). The results indicate the presence of two flavonoid compounds, namely Apigenin 6,8-di-C-|A-L-Arabinopyranoside and 3-Methylquercetin, and three phenol compounds, namely 3-Hydroxytrisol 3-O-glucoside, 4-Hydroxy-3-methoxyacetate, and Hydroxytrisol. Two compounds exhibited high bioactive potential (Pa value > 0.7), two compounds showed medium bioactive potential (Pa value > 0.5), and one compound exhibited low bioactive potential (Pa value < 0.5). The most bioactive compounds were Apigenin 6,8-di-C-|A-L-Arabinopyranoside and 3-Methylquercetin. The compounds with medium bioactivity were 3-Hydroxytrysol 3-O-glucoside and 4-Hydroxy-3-methoxycinnamic. The PASS online analysis revealed the potential of antioxidants for medicinal potencies

Phytocompounds from Phyllanthus acidus (L.) Skeels in the management of Monkeypox Virus infections

Monkeypox is a communicable disease similar to smallpox, primarily occurring in African countries. However, recently it has spread to countries outside Africa and may arise as the next threat after COVID-pandemic. The causative organism, i.e. Monkeypox Virus (MPV) spreads from one individual to another primarily through inhalation of respiratory droplets or through contact with skin lesions of infected individuals. No known drugs are available specifically for MPV. Due to its similarity with smallpox, treatment of monkeypox is being attempted through the administration of the smallpox vaccine. Therefore, we evaluated the efficacy of the plant Phyllanthus acidus against MPV since it is traditionally used in the treatment of chickenpox and smallpox. Through functional annotation, PASS prediction and Network pharmacology analysis, the effectiveness of these chosen P. acidus-derived phytocompounds against MPV was confirmed. Target prediction of the phytocompounds identified in GC-MS analysis of the plant extract showed them to be associated with 76 human proteins. The compounds also show good binding affinity with selected viral proteins: DNA polymerase (DNApol), Putative Virulence Factor (vPVF) and Cytokine Binding Protein. Prediction of Activity Spectra for Substances (PASS) and functional annotation of the target proteins further support their antiviral nature through interaction with these proteins. The compounds were found to modulate pathways related to symptoms of viral infection and this may help in maintaining homeostasis. Our study demonstrates antiviral activity as well as the therapeutic potential of the plant against MPV infection.Communicated by Ramaswamy H. Sarma

Rosmarinic acid: Potential antiviral agent against dengue virus - In silico evaluation

A number of dengue viruses can seriously impact public health, and their spread has long been a concern. The development and administration of antiviral drugs have played a crucial role in combating viral infections in recent years. These drugs have shown that they can effectively inhibit viral replication and alleviate associated viral complications. The aim of this article is to provide an overview of current evidence on the effectiveness of administered antiviral drugs in controlling viral replication and treating viral problems. In the present study, the PyRx tool was used to produce proteins and ligands. In summary, the present study shows that rosmarinic acid has remarkable docking values against various dengue viral targets. Specifically, it shows a docking value of −8.0 for DENV1-E111, -8.1 for the RNA-dependent RNA polymerase (NS5), −8.2 for the non-structural A chain protein 1 (NS1), and −8.6 for the RNA helicase. These results suggest that rosmarinic acid may have an antiviral effect against the virus's target proteins. Further research is needed to investigate the therapeutic effects of rosmarinic acid in fighting viral infections. In addition, many enzymatic activities of rosmarinic acid have been reported by the PASS (Prediction of Activity Spectra for Substances) tool. The present investigation led to the definitive conclusion that rosmarinic acid possesses remarkable antiviral properties. The present study is promising for future applications, particularly in the search for a drug molecule that can effectively combat a variety of viral infections.

КОМПЛЕКС ФЕНОЛЬНЫХ СОЕДИНЕНИЙ ЭКСТРАКЦИОННЫХ ПРЕПАРАТОВ ИЗ ТРАВЫ ТИМЬЯНА МАРШАЛЛА: ПРОГНОЗИРОВАНИЕ БИОЛОГИЧЕСКОЙ АКТИВНОСТИ МЕТОДОМ IN SILICO

Abstract. Introduction. Currently, Marschall thyme herb (Thymus marschallianus) is currently not an officially used medicinal herbal raw material; however, it is widely used in folk medicine as an analgesic, wound healing, expectorant, and antispasmodic remedy. During phytochemical studies, it was found that the herb contains phenolic compounds represented by the aglycones of flavonoids, such as luteolin or apigenin, their 7-O-glycosides, and hydroxycinnamic acids, such as caffeic and rosmarinic acid. Aim. To predict the biological activity profile and related mechanisms of action of the complex of polyphenol compounds of extractive Marschall thyme herb preparations. Materials and Methods. The research focused on the polyphenolic complex compounds of infusion and tincture from Marschall thyme collected in Altai Krai. For computer-aided prediction of the biological activity of phenolic compounds, the PASS (Prediction of Activity Spectra for Substances) method was used, which allows predicting the activity profile of compounds from the structural formula based on the analysis of the structure–activity relationships. Results and Discussion. The study found that for all compounds, it can be assumed with a high probability to be antioxidant and membrane-protective activity, which may be associated with the suppression of oxidation processes by binding free oxygen, free radicals, and inhibition of free radical formation-responsible enzymes. For caffeic acid, apigenin, luteolin and their glycosides, the predicted types of activity and mechanisms of action aimed at suppressing the inflammatory process. For the sum of flavonoids, the manifestation of cytostatic and antineoplastic activities is expected. Conclusions. Polyphenolic complex of the infusion and tincture of Marschall thyme herb can potentially inhibit oxidative processes, stabilize cell cycle and suppress pathological exudative and proliferative processes. To assess the credibility of the prognosis, the results should be tested in real in vitro and in vivo studies.

Exploring the antiviral potency of γ-FP and PA compounds: Electronic characterization, non-covalent interaction analysis and docking profiling with emphasis on QTAIM aspects

As focuses on a set of pertinent compounds that incorporate a γ-substituted halophenol linkage with pentanamide (PA). The properties of these compounds were comprehensively assessed through various analytical techniques, including density functional theory (DFT) calculations, offering insights into their geometry and electronic energy gap characteristics. Charge delocalization and stability were explored via natural bond orbital (NBO) analysis. The chemical reactivity was further scrutinized by evaluating NBO, Molecular Electrostatic Potential (MEP), Hirshfeld surface analysis and Fukui functions. The compounds were found to exhibit stability attributed to a robust hydrogen bonding network, which was corroborated by Interaction Region Indicator (IRI) and Electron Density (ED) assessments. Additionally, pharmacological properties were predicted using the PASS (Prediction of Activity Spectra for Substances) server. Molecular docking studies suggested potential antiviral and antioxidant properties, particularly concerning carbonic anhydrase. The overall results imply that these compounds possess favorable drug-like characteristics and show promise for biological efficacy. The study also includes a 2D interaction profile image of the four most interacted proteins and a Ramachandran plot to elucidate the stereochemistry of a selected protein. Furthermore, the activities of 6FDM were investigated following a comprehensive literature survey, with detailed findings presented.

Exploring the potential of fluoro‐flavonoid derivatives as anti‐lung cancer agents: DFT, molecular docking, and molecular dynamics techniques

AbstractThe present investigation utilized in silico methodologies to explore the diverse pharmacological activities, toxicity profiles, and chemical reactivity of a series of fluoro‐flavonoid compounds (1–14), which are secondary metabolites of plants known for their broad range of biological effects. A comprehensive strategy is utilized, incorporating methods such as prediction of activity spectra for substances (PASS) prediction, absorption, distribution, metabolism, excretion, and toxicity (ADMET) assessments, and density functional theory (B3LYP) calculations using three basis sets: 6‐31G(d,p), 6‐311G(d,p), and 6‐311++G(d,p). Furthermore, the study employed molecular docking technique to identify target proteins, including HER2 (7JXH), EGFR (4UV7), FPPS (1YQ7), HPGDS (1V40), DCK (1P60), and KEAP1 on Nrf2 (1X2J), for the investigated compounds, with cianidanol and genistein serving as reference drugs for the docking process. The investigated fluoro‐flavonoid compounds exhibited significantly greater binding affinities (ranging from −8.3 to −10.6 kcal mol−1) toward HER2, HPGDS, and KEAP1 compared to the reference drugs, cianidanol and genistein, which displayed binding affinities ranging from −8.4 to −9.4 kcal mol−1. Furthermore, molecular dynamics simulations were conducted to assess the stability of the protein‐ligand interaction, using the root‐mean‐square deviation (RMSD), root‐mean‐square fluctuation (RMSF), Radius of gyration (Rg) parameters and principle component analysis (PCA). Among the tested fluoro‐flavonoid analogs, analog 11 showed a RMSD value of .15 nm with the HER2 protein target, indicating a stable interaction. Based on in silico results, it appears that the fluoro‐flavonoid compound 11 has the potential to serve as a targeted anti‐lung cancer drug. However, additional in vivo and in vitro studies are necessary to confirm this hypothesis.

The role of PASS and STITCH in the verification of unknown properties of pyruvate and lactate. Literature review and fragments of authors’ own research

The aim of the study was to identify the predicted spectrum of biological activity of pyruvate and lactate using modern computer modeling methods and to determine potential protein partners in intermolecular interaction.Materials and methods. The biological activity spectrum of pyruvate and lactate by the structural formula was determined using the PASS (Prediction of Activity Spectra for Substances) software. Potential protein interaction partners for small molecules were predicted using the Search Tool for Interactions Chemicals (STITCH).Results. Analyzing the obtained results in silico reveals that pyruvate and lactate exhibit diverse biological activities, molecular mechanisms, and pharmacological effects. These include regulation of lipid, protein, and carbohydrate metabolism and effects on enzyme activity and gene expression. The data on the antihypoxic, antiischemic, antitoxic, immunomodulatory, antiinflammatory, antiviral, vasoprotective, and cytoprotective effects are presented. The neuroprotective and antineurotoxic effects of pyruvate and lactate are predicted.Conclusion. The spectrum of biological activities of lactate and pyruvate were revealed by computer modeling methods, and protein interaction partners were characterized. The small molecules we studied have a coordinating role in the functioning and modulation of mediator, hormonal, receptor, immune, inflammatory, antibacterial, and antiviral responses and gene expression. The use of natural intermediates as therapeutic agents for the treatment of ischemic stroke, acute neurological disorders, and neurodegeneration is discussed, which is underlain by the stimulating effect of metabolites on neuroplasticity. These properties may be manifested through conformational rearrangement of receptors, active binding centers, expression of multiple genes, and changes in the functional manifestations of catalytic and other proteins. The obtained data will obviously expand our understanding of the role of small molecules in intermolecular metabolite – protein interactions.

In silico analysis of small molecules from Spirulina platensis as a loop dierutic and anti-inflammatory agent

Spirulina platensis has been used as food for centuries by different populations and has only been rediscovered in recent years. Once classified as the - blue-green algae’’, it does not strictly speaking belong to the algae, even though for convenience it continues to be referred to in that way. The current study aimed to explore the potential of Spirulina platensis extract as a loop diuretic and anti-inflammatory agent in silico. Gas Chromatography-Mass Spectrometry was used to identify the bioactive compounds in the Spirulina platensis extract. Seventeen bioactive compounds found from Spirulina platensis were then analyzed the loop diuretic-related activity using the Prediction of Activity Spectra for Substances (PASS) server. Furthermore, the SwissADME web server and ProTox II were used to evaluate drug-likeness, excretion, metabolism, distribution, absorption, and toxicity of the small molecule from Spirulina platensis based on PASS online prediction. There were 13 compounds found in Spirulina platensis that are related to loop diuretic and anti-inflammatory properties. Furthermore, several small molecules of Spirulina platensis (SP) have good bioavailability based on Swiss ADME analysis. Most of the Spirulina platensis small molecules followed the Lipinski rules and had high gastrointestinal (GI) absorption values. Based on these findings, small molecules of Spirulina platensis have the potential to act as loop diuretic and anti-inflammatory agents.

Computer‐aided evaluation of targets and biological activity spectra for new piperidine derivatives

<b>Background:</b> The unique ability of piperidine to combine with various molecular fragments makes it possible to use its chemical structure to create new drugs with potential pharmacological effects. However, preliminary studies are required to predict the activity of new compounds in order to determine the direction of further preclinical studies.<br /> <b>Aim: </b>This study aims at determining the potential targets and spectrum of biological activity of new piperidine derivatives by the <i>in silico</i> method.<br /> <b>Material and methods: </b>Prediction of the effects on targets and the spectrum of biological activity of three new piperidine derivatives synthesized at the Bekturov Institute of Chemical Sciences JSC was analyzed in this study. The chemical structures of these compounds were studied <i>in silico</i> using the web tool SwissTargetPrediction to identify the most likely protein targets. PASS (Prediction of Activity Spectra for Substances) online tool was used to predict the possible pharmacological activity of the studied compounds.<br /> <b>Results: </b>New modified piperidine derivatives are able to affect different enzymes, receptors, transport systems, voltage-gated ion channels, thereby providing a wide range of biological activities applicable in various fields of medicine. These substances represent interest in the treatment of cancer, central nervous system diseases, as local anesthetic, antiarrhythmic and antimicrobial agents, and are promising for pharmacological activity demonstration in preclinical studies.<br /> <b>Conclusion</b>: A comprehensive analysis of the above results leads to the conclusion that the compounds under study should be considered as potential substances for the design of new highly effective medicinal agents with a wide range of practical applications.

Click chemistry as a method for the synthesis of steroid bioconjugates of bile acids derivatives and sterols

Six steroid conjugates of bile acids and sterol derivatives have been synthesized using the click chemistry method. The azide-alkyne Huisgen cycloaddition of the propionyl ester of lithocholic, deoxycholic and cholic acid with azide derivatives of cholesterol and cholestanol gave new bile acid–sterol conjugates linked with a 1,2,3-triazole ring. Previously, sterols were converted to bromoacetate substituted derivatives by reaction with bromoacetic acid bromide in anhydrous dichloromethane. These compounds were then converted to azide derivatives using sodium azide. The propiolic esters of lithocholic, deoxycholic and cholic acids were obtained by reaction with propiolic acid in the presence of p-toluenesulfonic acid. Additionally, two of these steroids: methyl 3α-propynoyloxy-12α-acetoxy-5β-cholane-24-oate and methyl 3α-propynoyloxy-7 α,12α-diacetoxy-5β-cholane-24-oate were also obtained and characterized for the first time. All conjugates were obtained in good yields using an efficient synthesis method. The structures of all conjugates and the four substrates were confirmed by spectral (1H- and 13C NMR, FT-IR) analysis, mass spectrometry (ESI-MS), and PM5 semiempirical methods. The pharmacotherapeutic potential of the synthesized compounds was estimated based on the in silico Prediction of Activity Spectra for Substances (PASS) method. The cytotoxicity of the compounds was in vitro evaluated in a hemolytic assay using human erythrocytes as a cell model. The in silico and in vitro study results indicate that the selected compound possesses an interesting biological activity and can be considered as potential drug design agent. Additionally, molecular docking was performed for the selected conjugate.