Absorption, Distribution, Metabolism And Excretion Research Articles

Application of Machine Learning for the Prediction of Absorption, Distribution, Metabolism and Excretion (ADME) Properties from Cichorium intybus Plant Phytomolecules

Drug discovery is the process by which new drug candidates are discovered and drug development takes place. To enhance the efficiency, accuracy, and speed of the drug discovery process, machine learning (ML) could play a transformative role. For this research study, antidiabetic natural compounds from C. intybus, which is commonly known as chicory, were selected, as they have promising antidiabetic properties that can complement conventional diabetes treatments. A bioactive natural compound dataset was retrieved on the chicory plant using Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) public source information. This collected dataset was analyzed for its absorption, distribution, metabolism, and excretion (ADME) properties using the SwissADME online tool. Principal component analysis (PCA) and correlation analysis were performed using trial-version XLSTAT software 2014.5.03 and Python. The obtained dataset from SwissADME was subjected to cleaning, after that, it was used to develop machine learning models, such as support vacuum (SVM) ML, random forest (RF), Naive Bayes (NB), and decision tree (DT). The Lipinski rule of violation was chosen as the target variable. To improve the vitality of the created ADME dataset, PCA, a biplot graph, and correlation analysis were carried out. A large dataset of naturally occurring antidiabetic compounds was used to predict the drug-likeness of ML models that were effectively deployed on heterogeneous ADME datasets. Among all these ML models, DT performed better than the rest of the models.

Molecular docking, ADME properties and synthesis of thiophene sulfonamide derivatives

This study investigates the drug-like properties of target molecules containing thiophene sulfonamide groups (7a–7s) using computational molecular docking techniques. The binding interactions of these derivatives were assessed using protein 2NSD (Enoyl acyl carrier protein reductase InhA, complexed with N-(4-methylbenzoyl)-4-benzylpiperidine, PDB DOI: 10.2210/pdb2NSD/pdb) as the receptor. Molecular docking results revealed notable docking scores for all compounds, ranging from −6 to −12 kcal/mol. Compounds 7e, 7i, and 7f, in particular, demonstrated impressive glide scores (>11 kcal/mol) and were selected for further analysis through molecular dynamics simulations, which provided deeper insights into their dynamic behavior and stability. The drug-like properties of these molecules were evaluated based on Lipinski’s Rule of Five and ADME (Absorption, Distribution, Metabolism, and Excretion) criteria and compared with known drugs. Additionally, we synthesized these target molecules (7a–7s) using Suzuki-Miyaura coupling with a nickel catalyst replacing palladium. The chemical structures of the synthesized compounds were confirmed through elemental analysis, LC-MS,1H-NMR, and 13C-NMR spectroscopy.

Enzyme (α-Glucosidase, α-Amylase, PTP1B & VEGFR-2) Inhibition and Cytotoxicity of Fluorinated Benzenesulfonic Ester Derivatives of the 5-Substituted 2-Hydroxy-3-nitroacetophenones

The prevalence of small multi-target drugs containing a fluorinated aromatic moiety among approved drugs in the market is due to the unique properties of this halogen atom. With the aim to develop potent antidiabetic agents, a series of phenylsulfonic esters based on the conjugation of the 5-substituted 2-hydroxy-3-nitroacetophenones 1a–d with phenylsulfonyl chloride derivatives substituted with a fluorine atom or fluorine-containing (-CF3 or -OCF3) group were prepared. Their structures were characterized using a combination of spectroscopic techniques complemented with a single-crystal X-ray diffraction (XRD) analysis on a representative example. The compounds were, in turn, assayed for inhibitory effect against α-glucosidase, α-amylase, protein tyrosine phosphatase 1 B (PTP1B) and the vascular endothelial growth factor receptor-2 (VEGFR-2) all of which are associated with the pathogenesis and progression of type 2 diabetes mellitus (T2DM). The antigrowth effect of selected compounds was evaluated on the human breast (MCF-7) and lung (A549) cancer cell lines. The compounds were also evaluated for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The results of an in vitro enzymatic study were augmented by molecular docking (in silico) analysis. Their ADME (absorption, distribution, metabolism and excretion) properties have been evaluated on the most active compounds against α-glucosidase and/or α-amylase to predict their drug likeness.

IN SILICO ANALYSIS OF MOMORDICA CHARANTIA L. AS ANTIDIABETIC AGENTS THROUGH ACTIVATION OF HUMAN UDP-GALACTOSE 4-EPIMERASE RECEPTORS

This study investigates the antidiabetic potential of compounds found in Momordica charantia L., commonly known as bitter melon, through molecular docking and ADME (Absorption, Distribution, Metabolism, and Excretion) analysis. Utilizing in silico methods, several bioactive compounds from bitter melon, such as charantin, vicine, momordenol, momordicilin, and momordicoside, were evaluated for their ability to interact with the human UDP-Galactose 4-Epimerase receptor, a key enzyme involved in glucose metabolism. The docking results indicate that these compounds exhibit strong binding affinities, suggesting their role in glucose regulation. Further ADME analysis revealed that the compounds generally comply with the Lipinski Rule of Five, indicating favorable drug-like properties, though some compounds exhibited potential toxicities requiring further investigation. These findings highlight the potential of Momordica charantia as a source of antidiabetic agents, warranting additional in vivo and clinical studies to confirm their efficacy and safety in managing diabetes mellitus.

DFT, Molecular Docking, ADME, and Cardiotoxicity Studies of Persuasive Thiazoles as Potential Inhibitors of the Main Protease of SARS-CoV-2.

This study explores the capability of thiazoles as potent inhibitors of SARS-CoV-2 Mpro. Seventeen thiazoles (1-17) were screened for their linking affinity with the active site of SARS-CoV-2 Mpro and compared with the FDA-recommended antiviral drugs, Remdesivir and Baricitinib. Density Functional Theory (DFT) calculations provided electronic and energetic properties of these ligands, shedding light on their stability and reactivity. Molecular docking analysis revealed that thiazole derivatives exhibited favorable linking affinities with various functional sites of SARS-CoV-2 proteins, including spike receptor-linking zone, nucleocapsid protein N-terminal RNA linking zone, and Mpro. Notably, compounds 3, 10, and 12 displayed the best interaction with 6LZG as compared to FDA-approved antiviral drugs Remdesivir and Baricitinib, while compounds 1, 10, and 8 exhibited strong linking with 6 M3 M and also better than Remdesivir and Baricitinib. Additionally, compounds 3, 1, and 6 showed promising interactions with 6LU7 but only compound 3 performed better than Baricitinib. An ADME (Absorption, Distribution, Metabolism, and Excretion) study provided insights into the pharmacokinetics and drug-likeness of these compounds, with all ligands demonstrating good physicochemical characteristics, lipophilicity, water solubility, pharmacokinetics, drug-likeness, and medicinal chemistry attributes. The results suggest that these selected thiazole derivatives hold promise as potential candidates for further drug development.

ω‐Aminomethyl Longifolene Amide Derivatives: Synthesis, Crystal Structure, Hirshfeld Surface, DFT, Antimicrobial, and Molecular Docking Studies

AbstractTwelve novel ω‐aminomethyl longifolene amide derivatives (6 a–6 l) were synthesized and characterized. The intermolecular contacts and the relationship of structure‐property for the synthesized compounds were performed with the use of two‐dimensional fingerprint plots and Hirshfeld surface method. Moreover, the chemical reactivity and geometrical characteristics of target compounds were investigated using density functional theory (DFT) method. Molecular docking studies were performed to investigate the interactions between compounds 6 a–6 l and sortase A (SrtA) from S. aureus, the carboxy terminal domain of colicin E5 (E5‐CRD) and Serine/Threonine phosphatase Z1 (PPZ1) from C. albicans, respectively, and together with their biological activities. The docking results of the synthesized compounds 6 a–6 l showed different binding efficiencies and inhibitory effects on S. aureus, E. coli and C. albicans. Furthermore, preliminary antimicrobial activity assay showed that compounds 6 f, 6 i and 6 k exhibited comparable or superior antibacterial activity against S. aureus, B. subtilis and K. pneumoniae compared to rifampicin with minimum inhibitory concentration (MIC) values from 0.488 to 0.977 μg/mL. In addition, the absorption, distribution, metabolism and excretion (ADME) and drug‐likeness properties of the synthesized derivatives were evaluated as well.

Exploring the Potential Antidiabetic Effects of Alkannin (A Naphthoquinone Compound): In Vivo and In Silico Studies

Background It is estimated that the plant has been utilized in India’s traditional medical system for close to 2,500 years. Alkanin is a key active component in Boraginaceae medicinal plant roots. Many scientists are interested in this tiny molecule due to its biological potential. Purpose To examine the hypoglycemic effects of alkannin (a naphthoquinone pigment). Methods Initially, we determined the dosage of alkannin by conducting an acute oral toxicity study per Organisation for Economic Co-operation and Development guidelines. Subsequently, streptozocin was used to induce diabetes in mice, and we chose several parameters such as body weight, food and water intake, blood glucose level, and biochemical estimation for the in vivo evaluation. The enhanced pharmacokinetic features of alkannin, such as its better cytochromes P450 metabolism profiles and higher intestinal absorption as compared to glimepiride, were validated by in silico investigations utilizing Swiss ADME (Absorption, Distribution, Metabolism, and Excretion) and AutoDock Vina. Results In particular, blood glucose levels and body weight in the alkannin-treated group drastically decreased to 138 ± 1.45 mg/dL and 27.9±0.54 g, respectively, as compared with the diabetic-treated group. Moreover, alkaline phosphatase levels dropped to 57.26 ± 3.05 U/L in the alkannin group, suggesting enhanced liver and kidney functions. Creatinine levels also decreased from 1.44 ± 0.10 mg/dL to 0.92 ± 0.09 mg/dL, and serum glutamic oxaloacetic transaminase/aspartate aminotransferase levels decreased from 64.16 ± 3.14 U/L to 47.85 ± 2.01 U/L. Additionally, diabetic controls maintained cholesterol levels between 102.1 ± 11.46 mg/dL and 93.53 ± 2.61 mg/dL. With a considerable binding score of –9.2 kcal/mol for alkannin, molecular docking demonstrated a high degree of binding efficiency and robust interaction with biological targets. The docking results revealed that alkannin exhibits drug-like properties. In addition, it satisfies the lead likeness requirement and has a lower synthetic accessibility score compared to glimepiride. Conclusion The results revealed the promising characteristics and positive outcomes of alkannin, underscoring its potential as a viable candidate for further investigation and prospective advancement as a treatment drug for diabetes.

Innovation in cancer pharmacotherapy through integrative consideration of germline and tumor genomes.

Precision cancer medicine is widely established, and numerous molecularly targeted drugs for various tumor entities are approved or in development. Personalized pharmacotherapy in oncology has so far been based primarily on tumor characteristics, e.g., somatic mutations. However, the response to drug treatment also depends on pharmacological processes summarized under the term ADME (absorption, distribution, metabolism, and excretion). Variations in ADME genes have been the subject of intensive research for more than five decades, considering individual patients' genetic makeup, referred to as pharmacogenomics (PGx). The combined impact of a patient's tumor and germline genome is only partially understood and often not adequately considered in cancer therapy. This may be attributed, in part, to the lack of methods for combined analysis of both data layers. Optimized personalized cancer therapies should, therefore, aim to integrate molecular information about the tumor and the germline, taking into account existing PGx guidelines for drug therapy. Moreover, such strategies should provide the opportunity to consider genetic variants of previously unknown functional significance. Bioinformatic analysis methods and corresponding algorithms for data interpretation need to be developed to consider PGx data in interdisciplinary molecular tumor boards, where cancer patients are discussed to provide evidence-based recommendations for clinical management based on individual tumor profiles. Significance Statement The era of personalized oncology has seen the emergence of drugs tailored to genetic variants associated with cancer biology. However, full potential of targeted therapy remains untapped due to the predominant focus on acquired tumor-specific alterations. Optimized cancer care must integrate tumor and patient genomes, guided by pharmacogenomic principles. An essential prerequisite for realizing truly personalized drug treatment of cancer patients is the development of bioinformatic tools for comprehensive analysis of all data layers generated in modern precision oncology programs.

Computational investigation on the anti-tuberculosis potential of novel thiazinane derivatives

ABSTRACT Heterocyclic molecules, containing nitrogen, sulphur, oxygen, etc., have proven their significant roles in drug discovery. Mycobacterium tuberculosis has been one long-lasting disease for several decades and to date this disease, particularly those with multidrug resistance does not have highly efficient and potent therapeutics. The role of the methylcitrate cycle in detoxifying propionyl-CoA, a product formed from the metabolism of host cholesterol by Mtb is well known. Therefore, inhibiting key enzymes or pathways involved in this cycle could potentially influence the survival of the pathogen. Herein a small library of 16 new (Thiazinan-2-ylidene)pyridine-2-amine derivatives is investigated for their potential as anti-tuberculosis inhibitors via various computational methods like docking, dynamic simulations and ADME (absorption, distribution, metabolism and excretion). Further evaluations were carried out with online machine learning tools – mycoCSM and PAINS.

In-silico Investigation of Ginseng Phytoconstituents as Novel Therapeutics Against MAO-A.

Ginseng (Panax ginseng) is a herb of medicinal and nutritional importance. Ginseng has been used since ancient times for the treatment of numerous ailments as it has many therapeutic properties. Several phytoconstituents are present in Panax ginseng that possess a variety of beneficial pharmacological properties. To explore the potential of phytoconstituents of Panax ginseng in the treatment of depression, a molecular modeling technique was utilized targeting monoamine oxidase-A (MAO-A). A total of sixty-one phytoconstituents of ginseng were drawn with the help of ChemBioDraw Ultra 12.0 software and PDBs for MAO-A enzyme were retrieved from the RCSB PDB database. The prepared ligands were screened for MAO-A properties using the software Molegro Virtual Docker (MVD 2010.4.1.0). All the prepared ligands were evaluated for drug-likeliness properties using Swiss ADME. Among the docking studies of 60 Ginseng phytochemicals including one standard, 15 phytoconstituents with the highest dock score and better binding interactions were selected further for absorption, distribution, metabolism and excretion (ADME) studies. Stachyose (-227.287, 17 interactions), Raffinose (-222.157, 14 interactions), and Ginsenoside Rg1 (-216.593, 10 interactions) were found to possess better interactions as compared to Clorgyline taken as a standard drug. Stachyose was found to be the most potent inhibitor of MAO-A enzyme under investigation and can be a potential lead molecule for the development of newer phytochemical-based treatment of depression.

Novel 1,2,3-triazole derivatives containing benzoxazinone scaffold: Synthesis, docking study, DFT analysis and biological evaluation

In order to address the drastic demand for novel broad-spectrum antibacterial and anticancer medicines with enhanced activity, computer modelling was utilized to rationally develop newer anticancer triazole based drugs. A unique series of benzo[d][1,3]oxazin-4-one linked 1,2,3-triazoles was synthesised in five steps, with good yields and an assessment of their antibacterial and anticancer activities. IR spectroscopy, 1H NMR, 13C NMR, and mass spectrometry were used to characterize the synthesis of triazole compounds. From antibacterial screening, the prepared derivatives namely, 8a, 8e, 8h and 8k showed excellent inhibitory potential against S. aureus with ZI of 28 ± 0.48, 30 ± 0.42, 30 ± 0.11, 35 ± 0.23 mm respectively, compared to moxifloxacin (33 ± 0.15 mm). Compared to doxorubicin (IC50 = 2.45 ± 0.14 μM), compounds 8h and 8k demonstrated superior and exceptional cytotoxicity against the A549 cell line (IC50 = 2.30 ± 0.26 and 1.90 ± 0.30 μM, respectively). Latter All the derivatives were further subjected to in silico docking studies against human lung (PDB: 2P85), VEGFR2 kinase domain (PDB: 3CP9) and could serve as ideal leads for additional modification in the field of anticancer research. Based on docking results, 8e showed that the amino acids Arg373(A), Gly113(A), Glu103(A), Asp108(A), Ser119(A), Asn375(A), Val374(A), Lys387(A), and Asn120(A) exhibited highly stable binding to cytochrome P4502A13 receptor of lung cancer. Furthermore, Density Functional Theory (DFT) calculations are performed to support the molecular docking studies. Compounds 8e, 8h, and 8k were discovered to have estimated energy gaps (eV) of 3.181, 4.034, and 3.539 eV, respectively. Triazole 8h exhibited the lowest chemical hardness (1.962 eV) and the highest chemical softness (0.252 eV), which also suggests that it is more reactive than all the other compounds under study. Moreover, these scaffolds physicochemical characteristics, filtration molecular properties, assessment of toxicity, and bioactivity scores were assessed in relation to ADME (absorption, distribution, metabolism, and excretion). In conclusion, we discovered a novel benzoxazinone linked 1,2,3-triazoles with promising antimicrobial and anticancer activity and a favorable pharmacokinetic profile.

Molecular Docking and ADME Profiles of Hyrtiosulawesine Derivatives Targeting pfLDH: Exploring Potential as Antimalarial Agents

The relentless rise in Plasmodium falciparum’s resistance to existing antimalarial drugs has sparked an urgent quest for novel therapeutic agents. For centuries, natural resources have been the bedrock of medicinal remedies, with β-carboline emerging as a beacon of hope in antimalarial research. In this study, we delve into the potential of hyrtiosulawesine derivatives as revolutionary antimalarial compounds, utilizing hyrtiosulawesine as the crucial scaffold. Employing a sophisticated amalgamation of molecular docking and ADME (absorption, distribution, metabolism and excretion) profiling, we meticulously screened an extensive library of hyrtiosulawesine’s derivatives against P. falciparum. Based on advanced computational techniques, the binding affinities and interaction profiles were assessed and culminating in the selection of the most promising candidates based on their exceptional binding interactions. Moreover, the comprehensive ADME analyses were performed to assess the pharmacokinetic properties of these derivatives, ensuring their suitability as drug candidates. The results showed that most of the analogues exhibited strong binding affinities (-7.2 to -9.8 kcal/mol) to the Plasmodium falciparum lactate dehydrogenase (pfLDH) protein, surpassing that of hyrtiosulawesine itself. Among these, compounds 2t and 1w demonstrated the strongest binding, likely due to hydrogen bonding with Arg171 and Asn197. ADME profiling revealed that all hyrtiosulawesine derivatives displayed favourable drug-likeness properties and adhered to the Lipinski Rule of 5 (Ro5) indicating their potential efficacy as antimalarial agents. This investigation provides a foundation for further in vitro and in vivo investigations paving the way for the development of effective treatments against malaria.

Plant-Derived Flavonoids as AMPK Activators: Unveiling Their Potential in Type 2 Diabetes Management through Mechanistic Insights, Docking Studies, and Pharmacokinetics

Type 2 diabetes mellitus (T2DM) remains a significant global health issue, marked by insulin resistance and disrupted glucose metabolism. AMP-activated protein kinase (AMPK) serves as a key regulator of cellular energy balance, playing a crucial role in enhancing insulin sensitivity, promoting glucose uptake, and reducing glucose production in the liver. Recently, there has been growing interest in plant-derived flavonoids as natural activators of AMPK, offering a promising complementary approach to conventional diabetes treatments. This review delves into ten flavonoids identified as AMPK activators, including baicalein, dihydromyricetin, bavachin, 7-O-MA, derrone, and alpinumisoflavone. Their activation mechanisms are explored, which include both direct binding to the AMPK complex and indirect pathways involving upstream signaling. Through molecular docking studies, the binding affinities and interaction profiles of these flavonoids with AMPK are assessed, revealing varying levels of activation potential. Notably, baicalein and dihydromyricetin showed strong binding to the α1 subunit of AMPK, indicating high potential for robust activation. Additionally, this review provides a thorough analysis of the pharmacokinetic properties and drug-likeness of these flavonoids using the SwissADME tool, focusing on aspects such as ADME (Absorption, Distribution, Metabolism, and Excretion). While the overall profiles of these compounds are promising, issues like solubility and possible drug–drug interactions are areas that need further refinement. In summary, plant-derived flavonoids emerge as a promising avenue for developing new natural therapies for T2DM. Moving forward, research should aim at optimizing these compounds for clinical application, elucidating their specific mechanisms of AMPK activation, and confirming their efficacy in T2DM treatment. This review highlights the potential of flavonoids as safer and more holistic alternatives or adjuncts to current diabetes therapies.

IN-SILICOIDENTIFICATION OF FLAVONOIDS BASED INHIBITORS AGAINST SORTASE-A FROM ENTEROCOCCUS FAECALIS (Ef)

The enzyme known as SortaseA(SrtA) is widespread present in gram-positive bacteria. SrtA is responsible for anchoring a large number of surface protein virulence factors to the cell wall. This enzyme is not involved in bacterial growth and is also present on the cell membrane, which makes it more accessible for the design of inhibitors. In the case of Enterococcus faecalis (Ef), which is responsible for a wide range of nosocomial infections, SrtA from this organism promotes development of biofilm, which in turn makes bacteria resistant to antibiotics. Numerous inhibitors have been identified and characterized against Ef-SrtA; however, none have been clinically approved till now. Natural compounds and their derivatives showed inhibition against Ef-SrtA. In this work, a flavanoids-based in-house natural library was screened against Ef-SrtA to see how these molecules bind to active site of Ef-SrtA. Furthermore, the absorption, distribution, metabolism and excretion (ADME) properties of the top five compounds, Abyssinones lii, Apigenin, Rutin, Fisetin and Kaemferol, were calculated, Additionally, the correlation between the structure and function of these top five compounds was analyzed using Density Functional Theory (DFT) studies.

Experimental, quantum chemical spectroscopic investigation, topological, molecular docking/dynamics and biological assessment studies of 2,6-Dihydroxy-4-methyl quinoline

The present work is a comprehensive investigation of the spectral, electronic structure, bonding, and reactivity of the 2,6-dihydroxy-4-methylquinoline (26DH4MQ) molecule through a wide range of experimental and quantum chemical spectroscopic calculations techniques, along with its applications as nonlinear optical materials and biological assessments. The study utilized density functional theory (DFT) and time-dependent density functional theory (TD-DFT) with the B3LYP method and the 6-311G++(d,p) basis set to analyze the structural and molecular properties of 26DH4MQ. The findings from UV–Vis, FT-IR, and FT-NMR spectroscopy show a strong agreement between the experimentally obtained vibrational frequencies and chemical shifts and those predicted by computational methods. Local reactivity descriptors, such as the dual descriptor, Fukui functions, and the molecular electrostatic potential (MEP) map, were used to identify the reactive regions of the molecule. Additionally, natural bond orbital (NBO) analysis provided insights into the charge transfer characteristics of 26DH4MQ, which helps to stabilize the molecular system. The study also revealed notable nonlinear optical (NLO) properties, with polarizability (18.52 × 10–24e.s.u.) and first-order hyperpolarizability (2.26 × 10–30e.s.u.) values that surpass those of standard organic compounds, suggesting significant potential for optoelectronic applications. The biological evaluation of 26DH4MQ assessed its drug-likeness, toxicity, enzyme inhibition, and ADME (Absorption, Distribution, Metabolism, and Excretion) parameters, highlighting its pharmaceutical potential. Furthermore, molecular docking and dynamics studies illustrated the compound's interaction with proteins, indicating its potential role as an insulin inhibitor.

Development and validation of a prognostic signature of breast cancer based on drug absorption, distribution, metabolism and excretion (ADME)-related genes

The individual variation of carcinogenesis and drug response is influenced by the absorption, distribution, metabolism, and excretion (ADME) of drugs. The utilization of signatures derived from ADME-related genes holds potential for predicting prognosis and treatment response across diverse cancer types. Further investigation is required to completely understand the role of ADME-associated genes in breast cancer. A signature was constructed through the application of a least absolute shrinkage and selection operator regression model, employing prognostic differentially expressed genes found in both cancer tissue and normal tissue. To assess the robustness of the signature, verification analyses were carried out. RT-qPCR was utilized for the validation of gene expression related to risk. Subsequently, a nomogram was developed to enhance the clinical utility of our prognostic tool. The ADME signature, comprising four genes, was established and exhibited a robust association with the prognoses of individuals diagnosed with breast cancer. The nomogram was created by fusing the clinicopathological characteristics with the ADME signature. The ADME signature demonstrated remarkable superiority when compared to the performance of the other individual predictors. Additionally, the analysis of the immune microenvironment revealed that the ImmuneScores of the low-risk group were elevated. The variation in both the infiltration of immune cells and the expression of immune-related genes in the tissues differed among the two groups. For patients with breast cancer, the utilization of ADME signatures as biomarkers presents a significant reference point for prognosis and individualized treatment strategies.

Molecular docking analysis of Salvia sclarea flower extracts evaluated for protein target affinity based on different extraction methods

AbstractThis study evaluates the antioxidant activity and total phenolic, flavonoid, flavonol, and tannin contents of extracts obtained from the flower parts of Salvia sclarea using different extraction methods, such as maceration and rotavapor (RE). The results indicate that the maceration method yields extracts with higher antioxidant activity compared to the rotavapor method (DPPH IC50: 260.70 ± 65.41 mg/mL vs. 345.48 ± 27.91 mg/mL). Additionally, the maceration method produces higher values in terms of total phenolic (26.4 ± 7.78 mg GAE/g extract), flavonoid (10.44 ± 0.21 mg QE/g extract), flavonol (9.20 ± 0.84 mg QE/g extract), and tannin contents (8.36 ± 0.39 mg GAE/g extract), whereas the RE method shows lower values (phenolics: 19.8 ± 3.31 mg GAE/g extract, flavonoids: 10.35 ± 0.35 mg QE/g extract, flavanol's: 5.45 ± 0.01 mg QE/g extract, and tannins: 7.72 ± 0.10 mg GAE/g extract). The gas chromatography–mass spectrometry (GC–MS) analysis of the extracts identified various bioactive compounds. Molecular docking studies revealed that Terpinen‐4‐ol obtained through maceration exhibits a strong binding affinity to a specific protein target, indicating potential biological activity. The predicted pharmacokinetic (ADME (absorption, distribution, metabolism, and excretion)) parameters for Terpinen‐4‐ol suggest favorable absorption and central nervous system (CNS) penetration, while Squalene obtained through maceration shows different pharmacokinetic properties. S. sclarea highlights significant antioxidant potential and provides insight into the bioactive compounds obtained through different extraction methods. To further investigate the potential biological interactions arising from these differences, molecular docking studies were conducted.

Synthesis and antimicrobial activity of benzoxazine/benzothiazine appended 1,2,3-triazole hybrids

In the present context to rationalize the search for new effective antimicrobial agents against the infections caused by microbes, a series of benzoxazine/benzothiazine appended 1,2,3-triazole hybrids were designed and synthesized via click reaction with ingredients of two or more bioactive moieties through the concept of molecular hybridization. Various spectral techniques such as FTIR, 1H NMR, 13C NMR, 2D NMR and HRMS were utilized for structural elucidation of the synthesized hybrids. The serial dilution method was employed for performing the antimicrobial activity of synthesized triazoles against four bacterial (S. aureus, B. subtilis, E. coli, K. pneumoniae) and two fungal (C. albicans, A. niger) strains. The antibacterial results demonstrated that a couple of hybrids show noteworthy outcomes related to standard medication. Compound 4r was indicated great action against E. coli with MIC values 0.0259 µmol/mL. Based on outcomes of antibacterial activity, molecular docking study was carried out with E. coli DNA gyrase to understand the binding behavior. To check out the drug-likeness, in silico ADME (Absorption, Distribution, Metabolism and Excretion) studies of synthesized hybrids were also analyzed and found that compounds can be developed as potential oral drug candidates.

Synthesis, Characterization, Band gap calculation, DFT study and Biological implication of Two Nitrogen-rich Proligands: Polymorphic Crystal Structures and Hirshfeld surface analyses of a Thiocarbohydrazone

A novel dihydrazone proligand 1,3-bis(pyridin-4-ylmethylideneamino)guanidine hydrochloride (H3L1) is reported along with polymorphic crystal structures of an analogous proligand 1,5-bis(4-pyridinecarboxaldehyde) thiocarbohydrazone (H2L2. H2O & H2L2. 2H2O). The crystal systems of H2L2. H2O and H2L2. 2H2O are monoclinic with P21/c and C2/c space groups. Strong hydrogen bonding interactions are found to be predominate in the H2L2. 2H2O crystal lattice. Hirshfeld surface analysis reveals that, after isotropic H···H interactions, N···H and C···H interactions are found to have the highest contribution to the overall Hirshfeld surface areas of H2L2. H2O and H2L2. 2H2O respectively. The pore volume and surface area of the thiocarbohydrazone polymorphs are also calculated. Direct band gap energies for H3L1 and H2L2 in their solid-states were estimated as 2.33 and 2.58 eV respectively using the Kubelka-Munk model. Molecular geometry of both the compounds are optimised using density functional theory and quantum chemical parameters are calculated. Frontier molecular orbital energy gaps in the gas phase for H3L1 and H2L2 are found to be 4.49 and 3.55 eV respectively, which indicates strong intermolecular interaction in the solid lattice of H3L1. Absorption, distribution, metabolism and excretion (ADME) attributes indicate both compound's potential as drug candidates. In vitro antibacterial study reveals that the thiocarbohydrazone based proligand is a more efficient inhibitor against gram-positive Staphylococcus aureus bacterial species. The anticancer activities of the compounds against MCF-7 human breast cancer cells suggested that H3L1 with an IC50 value of 172.6798 µg/mL has more potent than H2L2 (IC50 value of 279.1881 µg/mL).

Synthesis, structure analysis, biological activity evaluation and pharmacological aspects prediction of two newly synthesized compounds: N-methylbenzylammonium bromide and 2-amino-5-ammoniopyridinium dichloride

Medical and pharmaceutical demands have driven the development of new synthetic materials. This study explores bioinspired materials from various intriguing biological compositions, focusing on functional and structural categories. In this context, two novel salts, (C8H12N),Br (I) and (C5H9N3),2Cl (II) were synthesized via slow evaporation at ambient temperature and characterized using multiple techniques. Their crystal packing is stabilized by non-covalent interactions, including N–H…Br, C–H…Br, C–H…Cl and N–H…Cl hydrogen bonds. Three-dimensional Hirshfeld surface analysis followed by two-dimensional fingerprint plots provides insights into the intermolecular interactions within the crystalline structure. The thermal decomposition of the compounds was analyzed using TGA-DTA techniques. The synthesized products were also evaluated for in vitro antifungal, antioxidant and antibacterial activities, revealing notable antioxidant properties. Additionally, molecular docking studies were conducted against the bacterial DNA gyrase of Staphylococcus aureus, Listeria monocytogenes, Salmonella enterica Typhimurium and Pseudomonas aeruginosa as well as the fungal chitin synthase enzyme of Aspergillus niger and Fusarium oxysporum. Based on the obtained free energies of binding (ΔG), compounds I and II demonstrated significant effects against the tested microorganisms by disrupting the topological state of bacterial genetic material and inhibiting fungal chitin formation. ADME (Absorption, Distribution, Metabolism and Excretion) prediction using SwissADME webserver suggest that these compounds have suitable pharmacokinetic profiles and could serve as promising drug candidates against various microbial infections.