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Biosynthesis techniques for nanomaterials have advanced significantly, promoting eco-friendly synthesis chemistry as a sustainable alternative to conventional methods. This study presents a novel and environmentally friendly approach for synthesizing nanoparticulate ZnO, CuO, and ZnO/CuO nanocomposites using aqueous extracts of Pleurotus ostreatus spent substrate, is reported. The structural, optical, and morphological properties of the synthesized NPs were analysed. A hexagonal phase of ZnO NPs and a monoclinic phase of CuO NPs were obtained according to the X-ray diffraction analysis. A reduction in the peak intensity of these metal oxides was observed in the ZnO/CuO NPs due to reduced crystallinity. The absorption spectra, obtained from the UV–vis analysis, showed peaks at 354, 365, and 525 nm for the ZnO, CuO, and ZnO/CuO NPs, respectively. An anticancer assay of the NPs was conducted using human embryonic kidney (HEK 293) and cervical carcinoma (HeLa) cell lines, while a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay was used for the antioxidant evaluation. The ZnO, CuO, and ZnO/CuO NPs showed higher antioxidant potency with IC50 of 2.15, 2.16, and 3.18 µg/mL, respectively, than the ascorbic acid (4.25 µg/mL). This indicates that the nanoparticles were more effective in capturing DPPH free radicals. Anticancer assays showed strong cytotoxic effects for all nanoparticles, with ZnO NPs exhibiting the highest activity (IC50: 1.94 μM for HEK 293 cells, 3.23 μM for HeLa cells), surpassing CuO and ZnO/CuO NPs. Cell viability for both HEK 293 and HeLa cells decreased as nanoparticle concentration increased, confirming dose-dependent cytotoxicity. The green synthesized metal oxides and their composite have the potential for biomedical applications. [ABSTRACT FROM AUTHOR]

Abstract Biosynthesis techniques for nanomaterials have advanced significantly, promoting eco-friendly synthesis chemistry as a sustainable alternative to conventional methods. This study presents a novel and environmentally friendly approach for synthesizing nanoparticulate ZnO, CuO, and ZnO/CuO nanocomposites using aqueous extracts of Pleurotus ostreatus spent substrate, is reported. The structural, optical, and morphological properties of the synthesized NPs were analysed. A hexagonal phase of ZnO NPs and a monoclinic phase of CuO NPs were obtained according to the X-ray diffraction analysis. A reduction in the peak intensity of these metal oxides was observed in the ZnO/CuO NPs due to reduced crystallinity. The absorption spectra, obtained from the UV–vis analysis, showed peaks at 354, 365, and 525 nm for the ZnO, CuO, and ZnO/CuO NPs, respectively. An anticancer assay of the NPs was conducted using human embryonic kidney (HEK 293) and cervical carcinoma (HeLa) cell lines, while a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay was used for the antioxidant evaluation. The ZnO, CuO, and ZnO/CuO NPs showed higher antioxidant potency with IC50 of 2.15, 2.16, and 3.18 µg/mL, respectively, than the ascorbic acid (4.25 µg/mL). This indicates that the nanoparticles were more effective in capturing DPPH free radicals. Anticancer assays showed strong cytotoxic effects for all nanoparticles, with ZnO NPs exhibiting the highest activity (IC50: 1.94 μM for HEK 293 cells, 3.23 μM for HeLa cells), surpassing CuO and ZnO/CuO NPs. Cell viability for both HEK 293 and HeLa cells decreased as nanoparticle concentration increased, confirming dose-dependent cytotoxicity. The green synthesized metal oxides and their composite have the potential for biomedical applications.

Wound healing represents a global public health problem when it is not treated correctly, which can cause complications for the patient, such as functional loss of an organ, amputation, and even death. At a biological level, wound healing involves a complex mechanism in which the immune system and cellular biochemical cascades intervene in a coordinated manner, whose development occurs in stages such as inflammation, proliferation, and remodeling. Therefore, therapies have been developed to accelerate wound healing and have proven effective. However, factors such as diabetes mellitus limit the healing process because it causes alterations in microvascular dysfunction, as well as in the inflammatory response and greater oxidative stress. This is reflected in an abnormal healing process; therefore, the search for healing compounds has become an area of interest. In this regard, medicinal plants have been used for centuries to treat wounds in different cultures in the world. Hence, this review documents the main plant species used in Latin America due to its great biodiversity and numerous species that are potentially important for the development of new active healing compounds. In this review, 62 plant families with wound healing studies were found, highlighting Fabaceae, Asteraceae and Euphorbiaceae family. Additionally, 32 natural compounds with diverse structural nature were found, whose effects have been evaluated in in vivo and in vitro models, which are essential for studying the pathogenesis of the tissue repair mechanism, detecting new biomarkers, and evaluate new treatments. Currently, several models are used to study the wound healing process, including in silico, in vitro, and in vivo models. On the other hand, there is no appropriate model to determine the wound healing effect, and, in many cases, they are combined to provide sufficient scientific evidence. Therefore, this review demonstrates that Latin America is a potential region for research into sources of healing molecules. Nevertheless, other species are still being studied whose scientific findings allow generating viable alternatives for the solution of health problems associated with wound healing.

The adoption of green chemistry protocols in nanoparticle (NP) synthesis has exhibited substantial potential and is presently a central focus in research for generating versatile NPs applicable across a broad spectrum of applications. In this scientific contribution, we, for the first time, examined the ability of Aconitum Laeve (A. Laeve) crude extract to synthesize silver and gold nanoparticles (AgNPs@AL; AuNP@AL) and explored their potential applications in biological activities and the catalytic degradation of environmental pollutants. The synthesized NPs exhibited a distinctive surface plasmon resonance pattern, a spherical morphology with approximate sizes of 5–10 nm (TEM imaging), a crystalline architecture (XRD analysis), and potential functional groups identified by FTIR spectroscopy. The antibacterial activity was demonstrated by inhibition zones that measured 16 and 14 mm for the AgNPs@AL and AuNP@AL at a concentration of 80 µg/mL against Staphylococcus aureus and 14 and 12 mm against Escherichia coli, respectively. The antioxidant potential of the synthesized NPs was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-Oxide (PTIO), and 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. Our findings suggest that the AuNP@AL effectively countered the tested radicals considerably, displaying IC50 values of 115.9, 103.54, and 180.85 µg/mL against DPPH, PTIO, and ABTS, respectively. In contrast, the AgNPs@AL showed IC50 values of 144.9, 116.36, and 95.39 µg/mL against the respective radicals. In addition, both the NPs presented significant effectiveness in the photocatalytic degradation of methylene blue and rhodamine B. The overall observations indicate that A. Laeve possesses a robust capability to synthesize spherical nanoparticles, exhibiting excellent dispersion and showcasing potential applications in both biological activities and environmental remediation. [ABSTRACT FROM AUTHOR]

Chamomile or camomile (Matricaria chamomilla L. syn. Matricaria recutita L.) belongs to the family Asteraceae. It is native to Europe and West Asia and has spread to other parts of the world. The plant essential oils and extracts have been frequently used for thousands of years in traditional and folk medicines across the world, due to their valuable medicinal properties. Currently, it is widely applied in different industries such as pharmaceutical, cosmetics, and food industry. Herein, the literature was carefully reviewed via search engines such as Google Scholar, Pub Med, and Scopus using keywords including biological activity, chamomile, flavonoids, pharmacological activity, Matricaria chamomilla, and Matricaria recutita. Sesquiterpenes such as bisabolol oxide B, bisabolone oxide, and bisabolol oxide A have been identified as the major constituents of chamomile essential oil. Also, various phenolic compounds and flavonoids were mostly reported as active compounds in the plant extracts. Although there are various reports pinpointing the mechanisms of action of chamomile and its constituents, some points have remained ambiguous and further well-designed clinical trials are required. Focusing on the importance of valuable biological properties of chamomile, the present review precisely discussed the characterized chemical constituents of the plant along with their mechanisms of action.

High throughput screening (HTS) technologies allow the biological testing of hundreds of thousands of compounds per day. Typically, a substantial proportion of the initial hits obtained by HTS are artifacts caused by assay interference. Therefore, global and technology-specific in silico models for identifying and predicting compounds interfering with biological assays have been developed. The global models benefit from training on large screening data sets, while the specialized models benefit from training on assay technology-specific experimental data. In this work, we develop and explore strategies for generating better predictors of technology-specific assay interference by utilizing the large bioactivity data matrices global models are trained on and employing partially new compound labeling approaches to maintain the assay technology awareness of specialized models. We demonstrate the utility of the statistically derived interference labels in machine learning using fluorescence-based assay interference as a representative example. Our random forest and multi-layer perceptron classifiers showed improved performance compared to existing models, achieving Matthews correlation coefficients (MCCs) of up to 0.47 on holdout data and up to 0.45 on an external test set. These results demonstrate that accurate assay-specific interference labels can be derived from large bioactivity data matrices, enabling the development of new machine-learning models without the need for further experimental data.

Multidrug-resistant tuberculosis (MDR-TB) continues to spread worldwide and remains one of the leading causes of death among infectious diseases. The enoyl-acyl carrier protein reductase (InhA) belongs to FAS-II family and is essential for the formation of the Mycobacterium tuberculosis cell wall. Recent years, InhA direct inhibitors have been extensively studied to overcome MDR-TB. However, there are still no inhibitors that have entered clinical research. Here, the ensemble docking-based virtual screening along with biological assay were used to identify potent InhA direct inhibitors from Chembridge, Chemdiv, and Specs. Ultimately, 34 compounds were purchased and first assayed for the binding affinity, of which four compounds can bind InhA well with KD values ranging from 48.4 to 56.2 µM. Among them, compound 9,222,034 has the best inhibitory activity against InhA enzyme with an IC50 value of 18.05 µM. In addition, the molecular dynamic simulation and binding free energy calculation indicate that the identified compounds bind to InhA with "extended" conformation. Residue energy decomposition shows that residues such as Tyr158, Met161, and Met191 have higher energy contributions in the binding of compounds. By analyzing the binding modes, we found that these compounds can bind to a hydrophobic sub-pocket formed by residues Tyr158, Phe149, Ile215, Leu218, etc., resulting in extensive van der Waals interactions. In summary, this study proposed an efficient strategy for discovering InhA direct inhibitors through ensemble docking-based virtual screening, and finally identified four active compounds with new skeletons, which can provide valuable information for the discovery and optimization of InhA direct inhibitors. [ABSTRACT FROM AUTHOR]

David C Rupp, David Canty, Catherine Rhéaume, Birgitte Sondergaard, Celina Niño, Ron S Broide, Amy D Brideau-Andersen Allergan Aesthetics, an AbbVie Company, Irvine, CA, USACorrespondence: David C Rupp, Allergan Aesthetics, an AbbVie Company, 2525 Dupont Drive, Irvine, CA, 92612, USA, Tel +1-714-246-4059, Email david.rupp@abbvie.comObjective: The goal of this study was to compare the unit-to-unit biological activity of the vacuum-dried formulation of prabotulinumtoxinA (prabotA) and onabotulinumtoxinA (onabotA) in preclinical assays.Methods: Reconstituted 100 U vials of prabotA and onabotA were tested in 3 distinct assays: plate-capture light chain activity (PC-LCA), measuringlight chain enzymatic activity after recovery of toxin from reconstituted product using a proprietary toxin capture step; cell-based potency assay (CBPA), measuring the intoxication steps of binding, translocation, and light chain activity (synaptosomal-associated protein 25 [SNAP25] cleavage); and mouse Digit Abduction Score (DAS), evaluating muscle paresis. Each assay tested 3 separate prabotA and onabotA lots on several independent test dates.Results: Multiple orthogonal assays established that when assessed on a unit-to-unit basis, the biological activity of prabotA is lower than that of onabotA. In the PC-LCA and CBPA assays, onabotA displayed 1.51 ± 0.14–fold higher (mean ± SD) and 1.33 ± 0.07–fold higher (mean of pooled lots ± SEM) activity than prabotA, respectively. Similarly, the mouse DAS data showed that onabotA had 1.4 ± 0.1–fold higher (mean ± SEM) potency than prabotA. Results of all 3 assays demonstrated differences in potency, efficacy, and duration of action between onabotA and prabotA on a unit-to-unit basis.Conclusion: Preclinical assays established differences in the biological activity of onabotA and prabotA, supporting that the units of biological activity are not interchangeable.Keywords: pharmaceutical preparations, biological assays, enzyme assays, animal studies, motor neurons, protein binding

Lumen structures exist throughout the human body, and the vessels of the circulatory system are essential for carrying nutrients and oxygen and regulating inflammation. Vasodilation, the widening of the blood vessel lumen, is important to the immune response as it increases blood flow to a site of inflammation, raises local temperature, and enables optimal immune system function. A common method for studying vasodilation uses excised vessels from animals; major drawbacks include heterogeneity in vessel shape and size, time-consuming procedures, sacrificing animals, and differences between animal and human biology. We have developed a simple, user-friendly in vitro method to form freestanding cell-laden hydrogel rings from collagen and quantitatively measure the effects of vasodilators on ring size. The hydrogel rings are composed of collagen I and can be laden with human vascular smooth muscle cells, a major cellular and structural component of blood vessels, or lined with endothelial cells in the lumen. The methods presented include a 3D printed device (which is amenable to future fabrication by injection molding) and commercially available components (e.g., Teflon tubing or a syringe) to form hydrogel rings between 2.6–4.6 mm outer diameter and 0.79–1.0 mm inner diameter. Here we demonstrate a significant difference in ring area in the presence of a known vasodilator, fasudil (p

Medicinal Chemistry is a quantitative scientific discipline. Hence, it is of utmost importance that scientists working in this field pay rigorous attention to the correct representation of their quantitative data. However, browsing the Medicinal Chemistry literature, it becomes obvious that this is very often not the case. In particular, results from biological assays are too frequently reported with unreasonable numbers of significant figures. In this Perspective, it is argued that this is poor practice that sheds an unfortunate light on the discipline of Medicinal Chemistry and that therefore, more rigorous policies regarding the presentation of quantitative data in Medicinal Chemistry publications should be considered., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Abstract Deep learning’s automatic feature extraction has been a revolutionary addition to computational drug discovery, infusing both the capabilities of learning abstract features and discovering complex molecular patterns via learning from molecular data. Since biological and chemical knowledge are necessary for overcoming the challenges of data curation, balancing, training, and evaluation, it is important for databases to contain information regarding the exact target and disease of each bioassay. The existing depositories such as PubChem or ChEMBL offer the screening data for millions of molecules against a variety of cells and targets, however, their bioassays contain complex biological descriptions which can hinder their usage by the machine learning community. In this work, a comprehensive disease and target-based dataset is collected from PubChem in order to facilitate and accelerate molecular machine learning for better drug discovery. MolData is one the largest efforts to date for democratizing the molecular machine learning, with roughly 170 million drug screening results from 1.4 million unique molecules assigned to specific diseases and targets. It also provides 30 unique categories of targets and diseases. Correlation analysis of the MolData bioassays unveils valuable information for drug repurposing for multiple diseases including cancer, metabolic disorders, and infectious diseases. Finally, we provide a benchmark of more than 30 models trained on each category using multitask learning. MolData aims to pave the way for computational drug discovery and accelerate the advancement of molecular artificial intelligence in a practical manner. The MolData benchmark data is available at https://GitHub.com/Transilico/MolData as well as within the additional files.

Cadmium sulphide (CdS) nanoparticles (NPs) were synthesized through hydrothermal route and characterized by UV-Vis spectroscopy, X-ray diffraction (XRD), Energy dispersive X-ray analysis, Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy and Thermo gravimetric analysis (TGA).The band gap of CdS nanoparticles was found to be 2.38 eV. CdS NPs are crystalline aggregates with hexagonal structure as shown by SEM and XRD analysis. TGA study revealed that the synthesized nanomaterials were very stable to temperature and only 6.54% total loss occurred during heating range (25 °C–600 °C).The CdS NPs were used for the first time against the degradation of Eosin B (EB) and Methyl green (MG) dyes in aqueous solution.The degradation of EB and MG over CdS nanocatalysts followed second order kinetics. The predicted activation energies for both the dyes' reactions were 61.1 kJ/mol and 32.11 kJ/mol, respectively. About 95% and 90% dye degradation was observed at the time interval of 160 minutes for EB and MG, respectively. High percent degradation of EB was observed at high pH (pH 0) while at low pH (pH 4) high percent degradation was found for MG dye. Maximum dye degradation was found at the optimal dose (0.03 g/L) of the catalyst and at low dye concentration. The rate of EB and MG dye degradation was found to increase with increase in temperature up to 45 °C. The recyclability study showed that CdS nanoparticles could be reused for the degradation of the given dyes. Good antibacterial activity against Staphylococcus aureus was shown by CdS NPs. From the biocompatibility it was confirmed that CdS NPS are bioincompatible compatible. HIGHLIGHTS The band gap was 2.38 eV.; Dyes degradation over followed second order kinetics.; 61.1 kJ/mol and 32.11 kJ/mol were activation energies.; 95% and 90% dye degradation was observed for EB and MG, respectively.; Good antibacterial activity against Staphylococcus aureus.; CdS NPS were found bioincompatible compatible.;

The title ligand (L"x), methyl 2-((4-cyanophenyl)(hydroxy)methyl)acrylate was synthesized following the Morita-Baylis-Hillman reaction scheme. Spectroscopic techniques such as: UV- Visible, FT-IR, ESI-MS, and 1H NMR helped in characterization of the L"x. Complexes of Cr3+, Co3+, Ni2+, Mn2+, Cu2+ with L"x were prepared and characterized by UV- Visible, FT-IR and powder-XRD. FTIR spectrum of the L"x generated through DFT B3LYP method and 6-311++ G (d,p) basis set was found in good agreement with experimental spectrum. Additionally, the semi-empirical PM6 method optimization helped propose the most suitable geometries of the complexes with Cr3+, Co3+ possessing octahedral, Ni2+ square planner, Mn2+ and Cu2+ tetrahedral geometries. Powder-XRD patterns of the complexes have revealed cubic crystal class for Cr3+ and Co3+, whereas hexagonal, orthorhombic, and monoclinic for Ni2+, Mn2+, and Cu2+ complexes were observed, respectively. In addition, the nano-particle size was found in the range of 8.2560–4.5316 nm for complexes. Antibacterial activity against S. aureus, E. coli, B. pumilis and S. typhi confirmed a substantially high potential, as endorsed by their Molecular docking studies, of Ni2+ and Cu2+ complexes against each bacterial strain. Moreover, all compounds exhibited positive antioxidant activities, but have no antifungal potential except L"x. The current study demonstrates the usefulness of these novel transition metal complexes as possible potent antibacterial and antioxidant agents. [ABSTRACT FROM AUTHOR]

Perinatal derivatives or PnDs refer to tissues, cells and secretomes from perinatal, or birth-associated tissues. In the past 2 decades PnDs have been highly investigated for their multimodal mechanisms of action that have been exploited in various disease settings, including in different cancers and infections. Indeed, there is growing evidence that PnDs possess anticancer and antimicrobial activities, but an urgent issue that needs to be addressed is the reproducible evaluation of efficacy, both in vitro and in vivo. Herein we present the most commonly used functional assays for the assessment of antitumor and antimicrobial properties of PnDs, and we discuss their advantages and disadvantages in assessing the functionality. This review is part of a quadrinomial series on functional assays for the validation of PnDs spanning biological functions such as immunomodulation, anticancer and antimicrobial, wound healing, and regeneration.

The acerola non-pomace, a by-product from the juice clarification step and rich in phenolic compounds and ascorbic acid, was investigated for its biological potential through in vitro tests. Extracts were obtained using hydrothermal extraction (HT) at 121°C as well as CO 2 -expanded ethanol (GXL) at 40°C. The GXL extract contained 159 mg/g of ascorbic acid, while the HT extract showed 70 mg/g. Catechin was found only in the HT extract, and quercetin only in the GXL extract. Both extracts exhibited similar antiglycemic potential, but the GXL extract showed twice the neuroprotective potential against acetylcholinesterase (AChE, IC 50 =302 μg/mL) and lipoxygenase (LOX, IC 50 =227 μg/mL) activities. In human breast cancer cells (MDA-MB-231), the GXL extract demonstrated better antitumor potential with an IC 50 of 100 μg/mL compared to 250 μg/mL for the HT extract. [Display omitted] • Acerola non-pomace extracts from hydrothermal (HT) and gas-expanded liquid (GXL) methods. • Ascorbic acid, phenolic compounds and antioxidant activity were determined in the extract. • GXL extract showed better anti-inflammatory and neuroprotective potential. • Both extracts were promising against the metabolic activity of human breast cancer cell. [ABSTRACT FROM AUTHOR]

[Display omitted] • Impedance to assess the biocompatibility and degradation of a cultured cell. • Cardiomyocyte cells seeded into poly(vinyl alcohol) and sodium alginate scaffold. • The dielectric parameters of the PVA/SA ratios to determine the cell impedance. • Three concentrations of PVA/SA were electrospunned: 3.5 wt%, 4 wt%, and 5 wt%. • The 5.0 wt% ratio showed the highest cell number with a more organized network. Achieving continuous cell growth on culture scaffolds indicates biocompatibility features in a biological system. On the other hand, a cell decrease indicates undesirable conditions of the scaffold. This study demonstrates that crushed poly(vinyl-alcohol) and sodium alginate (PVA/SA) scaffolds are detrimental to rat cardiomyocyte culture. The polymeric scaffold was produced by using the electrospinning technique. Three different PVA/SA concentrations were electrospun: 3.5 wt%, 4 wt%, and 5.0 wt%. The electrochemical impedance spectroscopy monitored the dielectric properties of the culture. The cellular study was carried out with Calcein-AM staining, while the architecture morphology was characterized with stereoscopic and optical microscopes. Results showed that the morphology and the cell proliferation rate depended on the PVA/SA concentration. The 5.0 wt% scaffold proved the most effective, given that it developed the highest impedance magnitude and the highest cell number with a more organized network formation. However, crushed scaffolds promoted a rapid cell decrease regardless of the PVA/SA ratio, since the cardiomyocyte cells did not form a biofilm on the electrospun-mats. Therefore, a homogenous scaffold is needed to guarantee biocompatibility features. [ABSTRACT FROM AUTHOR]

[Display omitted] • The Ir(III)-complexes were studied theoretically by using DFT /CAM-B3LYP level. • Molecular electrostatic potentials of the complexes were demonstrated. • CV results showed that the iridium-based variants have different redox potentials. • The compounds had antioxidant, antimicrobial and DNA binding activities. • Complex 6 had antibacterial activity against all test bacteria used. Mononuclear phosphinite Iridium complexes based on ferrocene group have been prepared and characterized by various spectroscopic techniques. The complexes were subjected to cyclic voltammetry studies in order to determine the energies of HOMO and LUMO levels and to estimate their electrochemical and some electronic properties. Organic complex-based memory substrates were immobilized using TiO 2 -modified ITO electrodes, and the memory functions of phosphinite-based organic complexes were verified by chronoamperometry (CA) and open-circuit potential amperometry (OCPA). Extensive theoretical and experimental investigations were directed to gain a more profound understanding of the chemical descriptors and the diverse electronic transitions taking place within the iridium complexes, as well as their electrochemical characteristics. The quantum chemical calculations were carried out for the iridium complexes at the DFT/CAM-B3LYP level of theory in the gas phase. Furthermore, the antioxidant, antimicrobial, DNA binding, and DNA cleavage activities of the complexes were tested. Complex 2 exhibited the highest radical scavenging activity (67.5 ± 2.24 %) at 200.0 mg/L concentration. It was observed that the complexes formed an inhibition zone in the range of 8–15 mm against Gram + bacteria and in the range of 0–13 mm against Gram – bacteria. The agarose gel electrophoresis method was used to determine the DNA binding and DNA cleavage activities of the complexes. All of the tested complexes had DNA binding activity; however, complexes 1, 2 , and 8 showed better binding activity than the others. [ABSTRACT FROM AUTHOR]

Two red-emitting heteroleptic iridium(III) complexes (Ir-p and Ir-q) were synthesized and their photophysical and biological properties were analyzed. After their structures have been confirmed by several techniques, such as 1H NMR, 13C NMR, FT–IR, UV–Vis, and MALDI TOF analyses, their luminescence behavior was investigated in ethanol and PBS (physiological medium, pH ~ 7.4) solutions. Emission spectra of both complexes are dominated by 3MLCT states at room temperature in ethanolic solution, but at 77 K the Ir-q exhibits the 3LC as the dominant emission state. The Ir-q complex shows one of the highest emission quantum yields, 11.5%, for a red emitter based on iridium(III) complexes in aerated PBS solution, with color coordinates (x;y) of (0.712;0.286). Moreover, both complexes display high potential to be used as a biological marker with excitation wavelengths above 400 nm, high water solubility (Ir-p 1838 μmol L−1, Ir-q 7601 μmol L−1), and distinct emission wavelengths from the biological autofluorescence. Their cytotoxicity was analyzed in CHO-k1 cells by MTT assays, and the IC50 was estimated as being higher than 131 μmol L−1 for Ir-p, and higher than 116 μmol L−1 for Ir-q. Concentrations above 70% of viability were used to perform cell imaging by confocal and fluorescence microscopies and the results suggest that the complexes were internalized by the cell membrane and they are staining the cytoplasm region. [ABSTRACT FROM AUTHOR]

Modern drug discovery employs a 'screening funnel' to pick compounds worthy of advancing to the clinic, a multi-step process linking a series of assays. Molecules which are active in in vitro assays are passed to a cell-based assay, etc. Each pair of assays may be discordant, due to their measuring similar but not identical properties. This can create an enormous potential to overlook the best molecules, which we highlight here through an understanding of relationships we call 'hit diffusion'. Understanding hit diffusion has important implications for structure-based design, and drug discovery overall. The biophysical bases for assay discordance are outlined, and some strategies for ameliorating the hit diffusion problem are described. [ABSTRACT FROM AUTHOR]

In mammalian cells, telomerase transcribes telomeres in large G-rich non-coding RNA, known as telomeric repeat-containing RNA (TERRA), which folds into noncanonical nucleic acid secondary structures called G-quadruplexes (G4s). Since TERRA G4 has been shown to be involved in telomere length and translation regulation, it could provide valuable insight into fundamental biological processes, such as cancer growth, and TERRA G4 binders could represent an innovative strategy for cancer treatment. In this work, the three best candidates identified in our previous virtual screening campaign on bimolecular DNA/RNA G4s were investigated on the monomolecular Tel DNA and TERRA G4s by means of molecular modelling simulations and in vitro and in cell analysis. The results obtained in this work highlighted the stabilizing power of all the three candidates on TERRA G4. In particular, the two compounds characterized by a chromene scaffold were selective TERRA G4 binders, while the compound with a naphthyridine core acted as a dual Tel/TERRA G4-binder. A biophysical investigation by circular dichroism confirmed the relative stabilization efficiency of the compounds towards TERRA and Tel G4s. The TERRA G4 stabilizing hits showed good antiproliferative activity against colorectal and lung adenocarcinoma cell lines. Lead optimization to increase TERRA G4 stabilization may provide new powerful tools against cancer. [ABSTRACT FROM AUTHOR]

A new hydrazide ligand was prepared to synthesize Ni(II), Hg(II) and UO2(II) complexes, which elucidated by all possible tools. Accordingly, 1M:2L molar ratio was suggested for Ni(II) and Hg(II) complexes, while UO2(II) complex close to 1:1 ratio. The ligand binds as a bidentate or tridentate mode either as a monobasic via deprotonation of azomethine group or as a neutral with Hg(II) complex. A square-planer geometry was suggested for [Ni(L)2], while the other complexes reveal octahedral geometry. The antimicrobial screening was performed as well as the antioxidant and cytotoxic activity test towards Ehrlich ascites cells. The ligand and its Ni(II) complex produce a notable inhibition for microorganisms, while their antioxidant and cytotoxicity are up to the standards themselves. The DFT/B3LYP and Hartree-Fock (HF) methods were used to optimize the structures under suitable basis sets to obtain essential parameters and 3D-maps. Utilizing Swiss-ADME link reveals the positive response of the ligand to blood brain barrier and human intestinal absorption. Moreover, other silico tests were performed via Pharmacophore and Molecular Operating Environmental module (MOE) against different proteins. Finally, the agreement between vitro and silico results was noticed with the ligand and its Ni(II)complex.

Deep learning's automatic feature extraction has been a revolutionary addition to computational drug discovery, infusing both the capabilities of learning abstract features and discovering complex molecular patterns via learning from molecular data. Since biological and chemical knowledge are necessary for overcoming the challenges of data curation, balancing, training, and evaluation, it is important for databases to contain information regarding the exact target and disease of each bioassay. The existing depositories such as PubChem or ChEMBL offer the screening data for millions of molecules against a variety of cells and targets, however, their bioassays contain complex biological descriptions which can hinder their usage by the machine learning community. In this work, a comprehensive disease and target-based dataset is collected from PubChem in order to facilitate and accelerate molecular machine learning for better drug discovery. MolData is one the largest efforts to date for democratizing the molecular machine learning, with roughly 170 million drug screening results from 1.4 million unique molecules assigned to specific diseases and targets. It also provides 30 unique categories of targets and diseases. Correlation analysis of the MolData bioassays unveils valuable information for drug repurposing for multiple diseases including cancer, metabolic disorders, and infectious diseases. Finally, we provide a benchmark of more than 30 models trained on each category using multitask learning. MolData aims to pave the way for computational drug discovery and accelerate the advancement of molecular artificial intelligence in a practical manner. The MolData benchmark data is available at https://GitHub.com/Transilico/MolData as well as within the additional files. [ABSTRACT FROM AUTHOR]

Compounds interfering with high-throughput screening (HTS) assay technologies (also known as “badly behaving compounds”, “bad actors”, “nuisance compounds” or “PAINS”) pose a major challenge to early-stage drug discovery. Many of these problematic compounds are “frequent hitters”, and we have recently published a set of machine learning models (“Hit Dexter 2.0”) for flagging such compounds.Here we present a new generation of machine learning models which are derived from a large, manually curated and annotated data set. For the first time, these models cover, in addition to target-based assays, also cell-based assays. Our experiments show that cell-based assays behave indeed differently from target-based assays, with respect to hit rates and frequent hitters, and that dedicated models are required to produce meaningful predictions. In addition to these extensions and refinements, we explored a variety of additional setups for modeling, including the combination of four machine learning classifiers (i.e. k-nearest neighbors (KNN), extra trees, random forest and multilayer perceptron) with four sets of descriptors (Morgan2 fingerprints, Morgan3 fingerprints, MACCS keys and 2D physicochemical property descriptors).Testing on holdout data as well as data sets of “dark chemical matter” (i.e. compounds that have been extensively tested in biological assays but have never shown activity) and known bad actors show that the multilayer perceptron classifiers in combination with Morgan2 fingerprints outperform other setups in most cases. The best multilayer perceptron classifiers obtained Matthews correlation coefficients of up to 0.648 on holdout data. These models are available via a free web service.

The edible plant, Piper guineense Schum and Thonn, belongs to the family Piperaceae and possesses insecticidal properties against stored product insects, but information on isolation and use of its amide alkaloids for the control of insect pests is scanty. Therefore, amide alkaloids from P. guineense fruits as well as its crude extract were investigated as protectant against Sitophilus zeamais Motschulschy (Coleoptera: Curculionidae), a cosmopolitan insect pest. Chemical analysis of P. guineense was done using chromatographic techniques and amide alkaloids were identified using liquid chromatography–quadrupole time of flight-mass spectrometry (LC-QToF-MS). The compounds were assayed on five pairs of two-day-old S. zeamais, feeding with the maize variety, TZPB-SR-W. All parameters, including mortality and oviposition by female S. zeamais, repellent effect of the compounds and their effects on maize seed germination, were evaluated relative to the synthetic chemical, pirimiphos-methyl and ethanol, as positive and negative controls, respectively. The six compounds identified were dihydrowisanine (1.01%), guineensine (0.22%), piperine (6.64%), piperlonguminine (0.25%), propiverine (0.16%) and trichostachine (3.80%). Guineensine and piperine caused the highest mortalities (97.5% and 82.5%, respectively) of S. zeamais, which were not significantly different from the mortality (100%) caused by pirimiphos-methyl. In addition, piperine treatment significantly reduced oviposition (0.75 per grain) when compared to ethanol-treated grains (5.00 per grain). There were no significant differences in per cent germination between maize seeds treated with the amide compounds and those included in the control groups (positive and negative controls). Amide alkaloids from P. guineense offer a useful source of biopesticide material for controlling S. zeamais. [ABSTRACT FROM AUTHOR]

[Display omitted] Oats are represented an important source for nutrition, and it have attracted a lot of attention in recent years. In this study we produced oatmeal cookies and oats was added to formula wheat by 50% and 75%. Also, we added cinnamon to treatments 3 and 4 by 5% to increase nutrition value of oatmeal cookies, improvement sensory evaluation and increase antioxidant properties. All the cookies treatments were storage at room temperature. The purposes of this study were to study antioxidant activity for oats and cinnamon. Also determined the chemical composition include (moisture content, protein, ash, total lipids, crude fibers, carbohydrates and total calories) for oats, white flour and oatmeal cookies treatments. In addition evaluated all of sensory evaluation contain (appearance, color, texture, taste and odor) and microbiological evaluation such as (total bacterial count, spore forming bacteria and mold and yeasts count) for oatmeal cookies treatments. Also, biological assays were preformed to measure level of GPT, GOT, urea, creatinine, total cholesterol, triglycerides, HDL, LDL, and glucose. Furthermore, histopathological examination of both liver and kidneys was analyzed. The obtained results were clarified that the antioxidant activity for oats and cinnamon were 52.91% and 87.91%. Moreover, addition of oats and cinnamon to the cookies improve sensory evaluation as made it more acceptable, decreasing microbial load principally treatments 4 (prepared by 75% oats + 5% cinnamon). Biochemical assays were improved in rats with cirrhosis of carbon tetrachloride and their histopathological examination of liver and kidneys. It was clear that the additions ground whole grain oats and cinnamon to wheat flour based cookies improve its nutritional, chemical, and biological functions properties. [ABSTRACT FROM AUTHOR]

With the pressure on coral reefs increasing, effective mapping of tropical coastal areas affected by anthropogenic nutrient input is essential in conserving existing reefs and to also restore reefs that may already be degraded. However, it is often difficult to detect the source of nutrients entering the reef ecosystem due to the rapid dilution and mixing of nutrients through currents, wave activity and other general mixing events. It is therefore recommended for water quality assessments that biological assays (bioassays) and chemical data are collected as well as biological and habitat data. A bioassay involves the use of a biological organism to test for the relative strength of a substance within the natural environment. This study attempts to quantify the amount, and find the source, of nutrient inputs into the marine environment on a developing tourist island in Thailand. Chemical data in the form of nutrient concentrations are used as an indication of the amount of nutrients present; while δ15N values in algae tissue are used to indicate the source of nutrients and whether or not they are of anthropogenic origin. A more detailed review of the current literature on tracing anthropogenic nutrient inputs using these methods is given below. Also reviewed is the current knowledge of the effects of nutrients on a coral reef ecosystem along with the various mechanisms involved.

Aim: Generating a data and software infrastructure for evaluating multi-target compound (MT-CPD) design via deep generative modeling. Methodology: The REINVENT 2.0 approach for generative modeling was extended for MT-CPD design and a large benchmark data set was curated. Exemplary results & data: Proof-of-concept for deep generative MT-CPD design was established. Custom code and the benchmark set comprising 2809 MT-CPDs, 61,928 single-target and 295,395 inactive compounds from biological screens are made freely available. Limitations & next steps: MT-CPD design via deep learning is still at its conceptual stages. It will be required to demonstrate experimental impact. The data and software we provide enable further investigation of MT-CPD design and generation of candidate molecules for experimental programs.

Aim: Providing compound data sets for promiscuity analysis with single-target (ST) and multi-target (MT) activity, taking confirmed inactivity against targets into account. Methodology: Compounds and target annotations are extracted from screening assays. For a given combination of targets, MT and ST compounds are identified, ensuring test data completeness. Exemplary results & data: A total of 1242 MT compounds active against five or more targets and 6629 corresponding ST compounds are characterized, organized and made freely available. Limitations & next steps: Screening campaigns typically cover a smaller target space than compounds from the medicinal chemistry literature and their activity annotations might be of lesser quality. Reported compound groups will be subjected to target set-based promiscuity analysis and predictions.

A basic problem in molecular biology is to estimate equilibrium states of biochemical processes. To this end, advanced spectroscopy methods have been developed in order to estimate chemical concentrations in situ or in vivo. However, such spectroscopy methods can require special conditions that do not allow direct observation of the biochemical process. A natural means of resolving this problem is to transmit chemical signals to another location within a lab-on-a-chip device; that is, employing molecular communication in order to perform spectroscopy in a different location. In this paper, we develop such a signaling strategy and estimation algorithms for equilibrium states of a biochemical process. In two biologically-inspired models, we then study via simulation the tradeoff between the rate of obtaining spectroscopy measurements and the estimation error, providing insights into requirements of spectroscopy devices for high-throughput biological assays. [ABSTRACT FROM AUTHOR]

ABSTRACT Non-renewable chemical products are still the most used for wood protection, however, they have negative aspects. Several problems associated with the extensive use of these substances have been reported, such as intoxication of animals and plants, and environmental contamination. This has led to a search for alternative methods of control that cause less impact on the environment. In this context, the use of natural products extracted from different plants can be an alternative to this industrial activity. The objective of this work was to evaluate the efficiency of andiroba, copaiba and jatropha oils, either pure or enriched with iodine (I2), to improve the biological resistance of Pinus elliottii wood to wood-decay fungi causing brown, white and soft rot. The andiroba and copaiba oils came from the state of Pará and the jatropha oil came from Paraíba. Thus, we performed resistance tests to accelerated decay (brown and white rot fungi) and soft rot tests in the laboratory. We used pure natural oils and those enriched with sublimated iodine in assessing efficiency. In turn, we evaluated the effects of volatilization and leaching on the efficiency of solutions against decaying fungi. Pure andiroba and jatropha oils were the least efficient in controlling the Trametes versicolor fungus in the accelerated decay biological assay. Moreover, the wood treated with pure copaiba oil (normal situation) was classified as non-resistant for controlling Postia placenta fungus. In the soft rot test, we observed that there was a tendency to improve the wood resistance (normal situation) with an increase in the iodine concentration (I2).

Lepidoptera is amongst one of the four most speciose insect orders and ecologically very successful because of their ability to fly. Insect flight is always aerobic and exacts a high metabolic demand on the animal. A family of structurally related neuropeptides, generically referred to as adipokinetic hormones (AKHs), play a key role in triggering the release of readily utilizable fuel metabolites into the hemolymph from the storage forms in the fat body. We used mass spectrometry to elucidate AKH sequences from 34 species of Lepidoptera and searched the literature and publicly available databases to compile (in a phylogenetic context) a comprehensive list of all Lepidoptera sequences published/predicted from a total of 76 species. We then used the resulting set of 15 biochemically characterized AKHs in a physiological assay that measures lipid or carbohydrate mobilization in three different lepidopteran species to learn about the functional cross-activity (receptor-ligand interactions) amongst the different butterfly/moth families. Our results include novel peptide structures, demonstrate structural diversity, phylogenetic trends in peptide distribution and order-specificity of Lepidoptera AKHs. There is almost an equal occurrence of octa-, nona-, and decapeptides, with an unparalleled emphasis on nonapeptides than in any insect order. Primitive species make Peram-CAH-II, an octapeptide found also in other orders; the lepidopteran signature peptide is Manse-AKH. Not all of the 15 tested AKHs are active in Pieris brassicae ; this provides insight into structure-activity specificity and could be useful for further investigations into possible biorational insecticide development. [ABSTRACT FROM AUTHOR]

The development of new molecules for the treatment of calmodulin related cardiovascular or neurodegenerative diseases is an interesting goal. In this work, we introduce a novel strategy with four main steps: (1) chemical synthesis of target molecules, (2) Förster Resonance Energy Transfer (FRET) biosensor development and in vitro biological assay of new derivatives, (3) Cheminformatics models development and in vivo activity prediction, and (4) Docking studies. This strategy is illustrated with a case study. Firstly, a series of 4-substituted Riluzole derivatives 1–3 were synthetized through a strategy that involves the construction of the 4-bromoriluzole framework and its further functionalization via palladium catalysis or organolithium chemistry. Next, a FRET biosensor for monitoring Ca2+-dependent CaM-ligands interactions has been developed and used for the in vitro assay of Riluzole derivatives. In particular, the best inhibition (80%) was observed for 4-methoxyphenylriluzole 2b. Besides, we trained and validated a new Networks Invariant, Information Fusion, Perturbation Theory, and Machine Learning (NIFPTML) model for predicting probability profiles of in vivo biological activity parameters in different regions of the brain. Next, we used this model to predict the in vivo activity of the compounds experimentally studied in vitro. Last, docking study conducted on Riluzole and its derivatives has provided valuable insights into their binding conformations with the target protein, involving calmodulin and the SK4 channel. This new combined strategy may be useful to reduce assay costs (animals, materials, time, and human resources) in the drug discovery process of calmodulin inhibitors. [Display omitted] • Synthesis, biosensors, cheminformatics, and docking strategy for drug discovery. • Chemical synthesis procedure for Riluzole derivatives from 4-bromoriluzole. • FRET biosensor for Ca2+-dependent CaM-ligands interactions monitoring for drugs. • Predictive model for multiple biological activity parameters in different brain regions. • Docking study of CaM-Riluzole derivatives interaction. [ABSTRACT FROM AUTHOR]

Abstract Diseases of infection, of neurodegeneration (such as Alzheimer’s and Parkinson’s diseases), and of malignancy (cancers) have complex and varied causative factors. Modern drug discovery has the power to identify potential modulators for multiple targets from millions of compounds. Computational approaches allow the determination of the association of each compound with its target before chemical synthesis and biological testing is done. These approaches depend on the prior identification of clinically and biologically validated targets. This Perspective will focus on the molecular and computational approaches that underpin drug design by medicinal chemists to promote understanding and collaboration with clinical scientists.

Intrinsically disordered proteins (IDPs) are emerging as attractive drug targets by virtue of their physiological ubiquity and their prevalence in various diseases, including cancer. NUPR1 is an IDP that localizes throughout the whole cell, and is involved in the development and progression of several tumors. We have previously repurposed trifluoperazine (TFP) as a drug targeting NUPR1 and, by using a ligand-based approach, designed the drug ZZW-115 starting from the TFP scaffold. Such derivative compound hinders the development of pancreatic ductal adenocarcinoma (PDAC) in mice, by hampering nuclear translocation of NUPR1. Aiming to further improve the activity of ZZW-115, here we have used an indirect drug design approach to modify its chemical features, by changing the substituent attached to the piperazine ring. As a result, we have synthesized a series of compounds based on the same chemical scaffold. Isothermal titration calorimetry (ITC) showed that, with the exception of the compound preserving the same chemical moiety at the end of the alkyl chain as ZZW-115, an increase of the length by a single methylene group (i.e., ethyl to propyl) significantly decreased the affinity towards NUPR1 measured in vitro, whereas maintaining the same length of the alkyl chain and adding heterocycles favored the binding affinity. However, small improvements of the compound affinity towards NUPR1, as measured by ITC, did not result in a corresponding improvement in their inhibitory properties and in cellulo functions, as proved by measuring three different biological effects: hindrance of the nuclear translocation of the protein, sensitization of cells against DNA damage mediated by NUPR1, and prevention of cancer cell growth. Our findings suggest that a delicate compromise between favoring ligand affinity and controlling protein function may be required to successfully design drugs against NUPR1, and likely other IDPs.

The antibiotic crisis has led to a pressing need for alternatives such as antimicrobial peptides (AMPs). Recent work has shown that these molecules have great potential not only as antimicrobials, but also as antibiofilm agents, immune modulators, anti-cancer agents and anti-inflammatories. A better understanding of the mechanism of action (MOA) of AMPs is an important part of the discovery of more potent and less toxic AMPs. Many models and techniques have been utilized to describe the MOA. This review will examine how biological assays and biophysical methods can be utilized in the context of the specific antibacterial and antibiofilm functions of AMPs.

The aim of the current study was to compare some biological activities of edible oils enriched with 10 % of cannabidiol (CBD samples) from the Slovak market. In addition, hemp, coconut, argan, and pumpkin pure oils were also examined. The study evaluated the fatty acids content, as well as antibacterial, antifungal, antioxidant, cytotoxic, and phytotoxic activities. The CBD samples presented antimicrobial activity against the tested bacterial strains at higher concentrations (10000 and 5000 mg/L) and antifungal activity against Alternaria alternata, Penicillium italicum and Aspergillus flavus. DPPH⋅ and FRAP assays showed greater activity in CBD-supplemented samples compared to pure oils and vitamin E. In cell lines (IPEC-J2 and Caco-2), a reduced cell proliferation and viability were observed after 24 hours of incubation with CBD samples. The oils showed pro-germinative effects. The tested activities were linked to the presence of CBD in the oils., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The metabolite profile of fresh Goji berries from two cultivars, namely Big Lifeberry (BL) and Sweet Lifeberry (SL), grown in the Lazio region (Central Italy) and harvested at two different periods, August and October, corresponding at the beginning and the end of the maturation, was characterized by means of nuclear magnetic resonance (NMR) and electrospray ionization Fourier transform ion cyclotron resonance (ESI FT-ICR MS) methodologies. Several classes of compounds such as sugars, amino acids, organic acids, fatty acids, polyphenols, and terpenes were identified and quantified in hydroalcoholic and organic Bligh-Dyer extracts. Sweet Lifeberry extracts were characterized by a higher content of sucrose with respect to the Big Lifeberry ones and high levels of amino acids (glycine, betaine, proline) were observed in SL berries harvested in October. Spectrophotometric analysis of chlorophylls and total carotenoids was also carried out, showing a decrease of carotenoids during the time. These results can be useful not only to valorize local products but also to suggest the best harvesting period to obtain a product with a chemical composition suitable for specific industrial use. Finally, preliminary studies regarding both the chemical characterization of Goji leaves generally considered a waste product, and the biological activity of Big Lifeberry berries extracts was also investigated. Goji leaves showed a chemical profile rich in healthy compounds (polyphenols, flavonoids, etc.) confirming their promising use in the supplements/nutraceutical/cosmetic field. MG63 cells treated with Big Lifeberry berries extracts showed a decrease of iNOS, COX-2, IL-6, and IL-8 expression indicating their significant biological activity.

Due to the increasing rate of morbidity and mortality caused by vector diseases in the current context, especially by Aedes aegypti, substances of plants have been studied as alternatives to chemical insecticides, among them, the essential oil (EO) of the species Cymbopogon winterianus. Thus, this study evaluated the larvicidal activity of the EO of C. winterianus against the A. aegypti larvae. EO was extracted through the hydro-distillation technique and physicochemical properties were determined. To evaluate larvicidal activity, tests were performed with larvae in the third instar at the final concentrations of 19.54; 26.50; 55.59; 138.98; 208.47 and 277.97 mg L-1 of C. winterianus EO. In addition, Artemia salina Leach bioassay was used to verify toxicity effect. EO obtained presented satisfactory results in 2.64%. In the larvicidal assay, 100% mortality of larvae was observed after 24 hours at concentrations of 208.47 mg L-1 and 277.97 mg L-1 of the EO, showed effective in the other concentrations and with LC50 of 46.18 mg L-1, considered highly active. In the toxicity assay, the EO presented LC50 at 532.34 mg L-1, showed considered nontoxic. These results reinforce the use of EO front A. aegypt larvae control. [ABSTRACT FROM AUTHOR]

• Biological implications were attributed to FDS ( F elicium d ecipiens S aponin). • Saponins isolated from several plants possess a broad spectrum of biological activities. • 12.8 μg/mL of FDS caused more than 99.9% Aspergillus cell death within 24 h. • The hemolytic activity inhibition of FDS was correlated to the Lectin concentration. Filicium decipiens saponin (FDS) is the first saponin purified from F. decipiens seeds using ion-exchange and gel filtration chromatographies. In the present study, FDS and the aqueous crude extract of F. decipiens seeds were examined for their antifungal properties, hemolytic/cytotoxicity activity. The dried seeds were powdered and homogenized in 10% (w/v) for the preparation of crude extract. Sample obtained from Sephadex-LH-20 demonstrated FDS with a peak at 752.35 g/mol. FDS showed the highest toxicity against Aspergillus flavus , presenting with a low fungicidal concentration at 12.8 μg/mL. Under hemolytic induction, rabbit and cow erythrocytes were more affected by both samples, and the inhibition effect of PpyLL lectin was observed. These characteristics provide fundamental understanding of F. decipiens secondary metabolites, which would benefit future research to prevent dangerous traditional uses and provide agricultural solution. [ABSTRACT FROM AUTHOR]

The antibiotic crisis has led to a pressing need for alternatives such as antimicrobial peptides (AMPs). Recent work has shown that these molecules have great potential not only as antimicrobials, but also as antibiofilm agents, immune modulators, anti-cancer agents and anti-inflammatories. A better understanding of the mechanism of action (MOA) of AMPs is an important part of the discovery of more potent and less toxic AMPs. Many models and techniques have been utilized to describe the MOA. This review will examine how biological assays and biophysical methods can be utilized in the context of the specific antibacterial and antibiofilm functions of AMPs. [ABSTRACT FROM AUTHOR]

Purpose: Preclinical testing of neurovascular devices is crucial for successful device design and is commonly performed using in vivo organisms such as the rabbit elastase-induced aneurysm model; however, simple in vitro models may help further refine this testing paradigm. The purpose of the current work was to evaluate, and further develop, tissue-engineered blood vessel mimics (BVMs) as simple, early-stage models to assess neurovascular devices in vitro prior to animal or clinical use. Methods: The first part of this work used standard straight-vessel BVMs to evaluate flow diverters at 1, 3, and 5 days post-deployment. The second part developed custom aneurysm-shaped scaffolds to create aneurysm BVMs. Aneurysm scaffolds were characterized based on overall dimensions and microstructural features and then used for cell deposition and vessel cultivation. Results: It was feasible to deploy flow diverters within standard BVMs and cellular linings could withstand and respond to implanted devices, with increasing cell coverage over time. This provided the motivation and foundation for the second phase of work, where methods were successfully developed to create saccular, fusiform, and blister aneurysm scaffolds using a wax molding process. Results demonstrated appropriate fiber morphology within different aneurysm shapes, consistent cell deposition, and successful cultivation of aneurysm BVMs. Conclusion: It is feasible to use tissue-engineered BVMs for assessing cellular responses to flow diverters, and to create custom aneurysm BVMs. This supports future use of these models for simple, early-stage in vitro testing of flow diverters and other neurovascular devices. [ABSTRACT FROM AUTHOR]

A straightforward and effective method to chemically conjugate hydroxypropyl cellulose (HPC) to GlcA is described via microwave assisted copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC) between the azide functionalized HPC and the alkynyl functionalized GlcA, reducing reaction times from 24 h to 2 h. Two types of HPC azide derivatives, including an ester (ES) or a carbamate (CB) functional group, were synthesized and characterized by FT-IR and NMR spectroscopy that revealed the efficiency in the incorporation of the azide moieties in the cellulose backbone. These compounds were then conjugated with the alkynyl GlcA by CuAAC, affording the desired glycopolymers, HPA-ES-GlcA and HPA-CB-GlcA in excellent yields. The whole process involved rapid and effective reactions as well as easy purification techniques, using mostly non-toxic solvents, contributing to the sustainability of the synthesis These glycopolymers were characterized by FT-IR, NMR, TGA, DTA and SEM. Furthermore, the cytotoxicity, anti-inflammatory and antibacterial properties of the new glycopolymers were tested and it was found that these new HPC-GlcA conjugates presented low cytotoxicity, good anti-inflammatory and antibacterial properties. Overall, our results showed that HPC-GlcA polymers are suitable as potential GAG mimics for biomedical applications, therefore further investigations will be carried out. • Successful functionalization of cellulose with azide using ester and carbamate linkages. • Successful functionalization of glucuronic acid with an alkyne. • Efficient preparation of glucuronic acid-cellulose glycopolymer using click chemistry. • The glycopolymer had low cytotoxicity, good anti-inflammatory and antibacterial properties. • The new glycopolymer is a potential glycosaminoglycan mimic for biomedical applications. [ABSTRACT FROM AUTHOR]

Predicting compounds with single- and multi-target activity and exploring origins of compound specificity and promiscuity is of high interest for chemical biology and drug discovery. We present a large-scale analysis of compound promiscuity including two major components. First, high-confidence datasets of compounds with multi- and corresponding single-target activity were extracted from biological screening data. Positive and negative assay results were taken into account and data completeness was ensured. Second, these datasets were investigated using diagnostic machine learning to systematically distinguish between compounds with multi- and single-target activity. Models built on the basis of chemical structure consistently produced meaningful predictions. These findings provided evidence for the presence of structural features differentiating promiscuous and non-promiscuous compounds. Machine learning under varying conditions using modified datasets revealed a strong influence of nearest neighbor relationship on the predictions. Many multi-target compounds were found to be more similar to other multi-target compounds than single-target compounds and vice versa, which resulted in consistently accurate predictions. The results of our study confirm the presence of structural relationships that differentiate promiscuous and non-promiscuous compounds.

Graphene oxide (GO)/peptide complexes as a promising disease biomarker analysis platform have been used to detect proteolytic activity by observing the turn-on signal of the quenched fluorescence upon the release of peptide fragments. However, the purification steps are often cumbersome during surface modification of nano-/micro-sized GO. In addition, it is still challenging to incorporate the specific peptides into GO with proper orientation using conventional immobilization methods based on pre-synthesized peptides. Here, we demonstrate a robust magnetic GO (MGO) fluorescence resonance energy transfer (FRET) platform based on in situ sequence-specific peptide synthesis of MGO. The magnetization of GO was achieved by co-precipitation of an iron precursor solution. Magnetic purification/isolation enabled efficient incorporation of amino-polyethylene glycol spacers and subsequent solid-phase peptide synthesis of MGO to ensure the oriented immobilization of the peptide, which was evaluated by mass spectrometry after photocleavage. The FRET peptide MGO responded to proteases such as trypsin, thrombin, and β-secretase in a concentration-dependent manner. Particularly, β-secretase, as an important Alzheimer’s disease marker, was assayed down to 0.125 ng/mL. Overall, the MGO platform is applicable to the detection of other proteases by using various peptide substrates, with a potential to be used in an automated synthesis system operating in a high throughput configuration.

Graphical abstract Highlights • Two novel acylthioureas (Ar-CO-NH-CS-NH-R) were synthesized and analyzed spectroscopically. • The crystal packing shows molecules arranged as dimers held by inter-molecular NH⋯S bonds. • The aromatic acyl thioureas could be considered as pseudo amino-enone systems for which the RAHB model is applicable. • One of the studied compounds can be used as agent to avoid surfaces contamination and as a disinfectant. Abstract The study of two new acylthiourea derivatives (Ar-CO-NH-CS-NH-R) are focused on the bonding interactions supported by X-ray, NMR, UV–Vis, Raman and IR spectroscopy, and NBO, AIM and Hirshfeld surface analysis. The RAHB model is proposed to explain some structural properties. The molecules are stabilized by intra-molecular NH⋯O bonds arranged in the lattice as centre-symmetric dimers held by inter-molecular NH⋯S bonds. The dimers are linked to each other through NH⋯O bonds giving rise to a chain, ribbon-like structure in the network. In vitro bacterial growth inhibition, biofilm formation, biosensor and biofilm metabolic activity were tested considering the broad bioactivity of acylthioureas. [ABSTRACT FROM AUTHOR]

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