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Formaldehyde, sulfuric acid and salicylic acid were combined to create a 3,3′-methylenebis(2-hydroxybenzoic acid) (MHB) ligand, which was subsequently permitted to bind with zinc(II) ions. The ligand and its zinc(II) complex (Zn–MHB) have been described by a combination of elemental analyses, spectral analyses (UV–Vis, IR, MS and NMR), XRD, TEM, as well as TGA measurement. The ligand has been suggested to coordinate to the zinc center in a tetradentate manner forming the binuclear tetrahedral complex. An X-ray analysis indicated a considerable difference between MHB (crystalline) and Zn–MHB (amorphous). The UV–Vis spectra were used to determine the optical properties such as bandgap, refractive index, optical conductivity and penetration depth. The possibility of employing the samples for optoelectronic applications was indicated from the band gap values which underlie the range of semiconductors. TEM revealed the spherical shapes and mutation of ligand particles into the nano-scale by complexation. The antimicrobial potential of the MHB towards Gram-positive and Gram-negative bacterial growths has been investigated. The results suggested that it would be possible to employ MHB to prevent bacterial development, particularly that of salmonella typhimurium. The cytotoxicity of the MHB was assessed against two types of mammalian cells: VERO (the kidney of an African green monkey) and HFB4 (human skin melanocytes). Lower sensitivity was observed in VERO cells.

This study focuses on the synthesis of novel vinpocetine derivatives (2–25) and their biological evaluation. The chemical structures of the synthesized compounds were fully characterized using techniques such as 1H NMR, 13C NMR, and HRMS. The inhibitory activity of the synthesized compounds on PDE1A was evaluated, and the results revealed that compounds 3, 4, 5, 12, 14, 21, and 25 exhibited superior inhibitory activity compared to vinpocetine. Compound 4, with a para-methylphenyl substitution, showed a 5-fold improvement in inhibitory activity with an IC50 value of 3.53 ± 0.25 μM. Additionally, compound 25, with 3-chlorothiazole substitution, displayed an 8-fold increase in inhibitory activity compared to vinpocetine (IC50 = 2.08 ± 0.16 μM). Molecular docking studies were conducted to understand the binding models of compounds 4 and 25 within the active site of PDE1A. The molecular docking study revealed additional binding interactions, such as π–π stacking and hydrogen bonding, contributing to the enhanced inhibitory activity and stability of the ligand–protein complexes. Overall, the synthesized vinpocetine derivatives demonstrated promising inhibitory activity on PDE1A, and the molecular docking studies provided insights into their binding modes, supporting further development of these compounds as potential candidates for drug research and development.

A series of new hydrazide (3 a–j) and pyridine (11 a–j) derivatives were synthesized using a convergent synthetic methodology by condensation of malono‐di(2‐phenylhydrazide) with arylidene malononitrile or arylidene ethyl cyanoacetate derivatives. The synthesized compounds (3, 11 a–j) were characterized using via IR, 1H‐, 13C‐NMR, and MS spectroscopies as well as elemental analysis. The biological activity of these molecules has been evaluated in vitro against two gram‐positive bacteria (Staphylococcus aureus and Streptococcus pneumoniae) and one‐gram negative bacteria (Escherichia coli), as well as one fungus (Candida albicans). The results of the bioactive assay revealed that the synthesized pyridine (11 a–j) derivatives had greater antibacterial efficacy than the hydrazide (3 a–j) derivatives and were comparable to the reference drug Augmentin. Furthermore, docking studies against the Staphylococcus aureus dihydrofolate reductase (DHFR) protein revealed that pyridine derivatives (11 a–j) had higher binding interactions affinity (ΔG=−9.59∼−7.69 kcal/mol) than diphenyl−malonohydrazide derivatives (3 a–j), which achieved a binding affinity in the range of (ΔG=−9.65∼−6.77 kcal/mol), supporting the experimental results. Finally, DFT and TD‐DFT were used to gain a better understanding of the structure‐activity relationship and biological activity of the new synthesized hydrazide/pyridine derivatives. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the chemical composition of the essential oils (EOs) from two Diplophyllum species and to evaluate their bioactivity potential [antimicrobial, antioxidant, anti-urease, anti-xanthine oxidase (XO)], and phenolic compounds. The analysis of Diplophyllum albicans and Diplophyllum taxifolium permitted the identification of 62 components, comprising = 99.6% of the total EO composition. The major components found in these liverwort species were ß-patchoulene, ß-santalene, ß-himachalene, and cubebol. The antimicrobial assays showed that the solvent extracts (n-hexane and methanol) from these liverwort species exhibited weak to moderate antimicrobial activity. In addition, the methanol extracts of these liverwort species also exhibited moderate to high antioxidant potential. The enzyme inhibitory effects of the species were determined using urease and XO for the methanol extracts. Generally, the methanol extracts of D. albicans and D. taxifolium exhibited powerful urease inhibition with IC50 values of 9.711 ± 0.058 and 6.304 ± 0.099 µg/mL, respectively, compared to the IC50 value of 26.124 ± 0.077 µg/mL for the standard (acetohydroxamic acid). Moreover, the HPLC-UV detection method showed that the analysed methanol extracts of these liverwort species contained only catechin and benzoic acid. These findings suggest that the analysed liverwort species possess antioxidant and urease inhibition, thus indicating the potential to explore new bioactive molecules. Cilj ove studije bio je da se ispita hemijski sastav eteričnih ulja (EO) dve vrste roda Diplophyllum i proceni potencijal bioaktivnosti [antimikrobna, antioksidantna, antiureazna, antiksantin oksidaza (KSO)] i fenolna jedinjenja. Kod Diplophyllum albicans i Diplophyllum taxifolium identifikovane su 62 komponente, koje čine = 99,6% ukupnog sastava EO. Glavne komponente nađene u ovim vrstama jetrenjača su ß-pačulen, ß-santalen, ß-himahalen, i kubebol. Antimikrobni testovi su pokazali da ekstrakti rastvarača (n-heksan i metanol) iz ovih vrsta jetrenjača pokazuju slabu do umerenu antimikrobnu aktivnost. Pored toga, metanolni ekstrakti ovih vrsta pokazali su umeren do visok antioksidativni potencijal. Enzimski inhibitorni efekti vrsta su određeni korišc'enjem ureaze i KSO za metanolne ekstrakte. Generalno, metanolni ekstrakti D. albicans i D. taxifolium su pokazali snažnu inhibiciju ureaze sa IC50 vrednostima 9,711 ± 0,058 i 6,304 ± 0,099 µg/mL, respektivno, gde je IC50 standarda (acetohidroksamične kiseline) 26,124 ± 0,077 µg/mL. Pored toga, HPLC-UV detekcija je pokazala da analizirani metanolni ekstrakti ovih vrsta jetrenjača sadrže samo katehin i benzoevu kiselinu. Ovi rezultati pokazuju da analizirane vrste jetrenjača poseduju antioksidantnu aktivnost i inhibiciju ureaze; te stoga poseduju potencijal za istraživanje novih bioaktivnih molekula. [ABSTRACT FROM AUTHOR]

KRASG12D, the most common oncogenic KRAS mutation, is a promising target for the treatment of pancreatic cancer. Herein, we identified four potent and noncovalent KRASG12D inhibitors (hits 1-4) by using structure-based virtual screening and biological evaluation. The in vitro assays indicated that the four compounds had sub-nanomolar affinities for KRASG12D and showed a dosedependent inhibitory effect on human pancreatic cancer cells. In particular, the hit compound 3 was the most promising candidate and significantly inhibited the tumor growth of pancreatic cancer in tumor-bearing mice. The hit compound 3 represented a promising starting point for structural optimization in hit-to-lead development. This study shows that hit compound 3 provides a basis for the development of the treatment of cancer driven by KRASG12D. [ABSTRACT FROM AUTHOR]

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Abstract Background Hemostasis plays a crucial role during every surgery allowing for a bloodless operating field. Fast and effective surgery leads to a reduced risk of postoperative complications. One of the latest methods for achieving homeostasis is using natural polysaccharide-based hemostatic powders. The study aimed to evaluate the biocompatibility according to the ISO 10993 standards of 4SEAL® Hemostatic powder. Methods Chemical characterization (Headspace GC-MS, GC-MS, and ICP-MS), cytotoxicity, genotoxicity (MLA and AMES), endotoxin contamination, sensitization potential, intracutaneous reactivity, acute and subacute systemic toxicity with implantation, and pyrogenicity were evaluated to investigate the biocompatibility of the 4SEAL® Hemostatic powder. Studies were conducted according to ISO 10993 standards. Results The biocompatibility requirements according to ISO 10993-1 for 4SEAL® Hemostatic powder were met. Based on the conducted in-vitro studies, 4SEAL® Hemostatic powder shows a non-cytotoxicity and non-mutagenic potential. Also, the results of in vivo studies of 4SEAL® Hemostatic powder shows no signs of toxicity, non-sensitizing, non-irritating, and no pyrogenicity potential. In the chemical characterization of 4Seal® Hemostatic Powder, no compounds were identified above Analytical Evaluation Threshold (AET) and no elements with concentrations higher than element-specific PDE [μg/day] were detected. Conclusions 4SEAL® Hemostatic powder is a promising new hemostatic agent with a wide range of potential applications and excellent biocompatibility.

[Display omitted] • Synthesis of new FePBZPHA, CoPBZPHA, and NiPBZPHA mixed-ligand complexes. • Stoichiometry determination confirming the 1:1:1 (M: PBZ: PHA) ratio; FT-IR spectra comparison elucidating intricate binding modes. • DFT calculations unveiling octahedral coordination geometries and enhanced electron affinity, electronegativity, and reactivity of metal complexes. • Biological evaluation showcasing significantly enhanced efficacy of metal complexes in antimicrobial, anti-inflammatory, and antioxidant activities, with FePBZPHA exhibiting the highest potency. • Molecular docking analysis highlighting potential therapeutic applications, with metal complexation enhancing binding affinity and interaction versatility. This study presents a thorough investigation into the synthesis, characterization, computational analysis, and biological evaluation of FePBZPHA, CoPBZPHA, and NiPBZPHA mixed-ligand complexes. They were synthesized in high yields via reactions between chloride salts of Iron, Cobalt, or Nickel with 2-(pyridin-2-yl)-1H-benzimidazole (PBZ) and Phenylalanine (PHA). They underwent extensive spectroscopic, elemental, conductivity, magnetic, and thermal analysis to confirm their formation. Molar conductivity measurements indicated their non-electrolytic nature, with UV–vis spectra revealing distinct absorption bands for PBZ and PHA ligands, shifting significantly upon metal ion coordination. Stoichiometry determination confirmed the 1:1:1 (M:PBZ:PHA) ratio, while FT-IR spectra comparison elucidated intricate binding modes, supported by mass spectra and elemental analysis. Thermal analysis revealed their thermal stability and decomposition pathways. DFT calculations unveiled octahedral coordination geometries and enhanced electron affinity, electronegativity, and reactivity of metal complexes. Biological evaluation showcased significantly enhanced efficacy of metal complexes in antimicrobial, anti-inflammatory, and antioxidant activities, with FePBZPHA exhibiting the highest potency. Molecular docking analysis highlighted their potential as therapeutic agents, with metal complexation enhancing binding affinity and interaction versatility. Overall, this study provides comprehensive insights into the synthesis, characterization, computational analysis, and biological evaluation of FePBZPHA, CoPBZPHA, and NiPBZPHA mixed-ligand complexes, suggesting promising applications in biomedicine and materials science. [ABSTRACT FROM AUTHOR]

Carbazole alkaloids, as an important class of natural products, have been widely reported to have extensive biological activities. Based on our previous three-component reaction to construct carbazole scaffolds, we introduced a methylene group to provide a rotatable bond, and designed series of carbazole derivatives with structural diversity including carbazole amide, carbazole hydrazide and carbazole hydrazone. All synthesized carbazole derivatives were evaluated for their in vitro cytotoxic activity against 7901 (gastric adenocarcinoma), A875 (human melanoma) and MARC145 (African green monkey kidney) cell lines. The preliminary results indicated that compound 14a exhibited high inhibitory activities on 7901 and A875 cancer cells with the lowest IC50 of 11.8 ± 1.26 and 9.77 ± 8.32 μM, respectively, which might be the new lead compound for discovery of novel carbazole-type anticancer agents.

KRASG12D, the most common oncogenic KRAS mutation, is a promising target for the treatment of pancreatic cancer. Herein, we identified four potent and noncovalent KRASG12D inhibitors (hits 1–4) by using structure-based virtual screening and biological evaluation. The in vitro assays indicated that the four compounds had sub-nanomolar affinities for KRASG12D and showed a dose-dependent inhibitory effect on human pancreatic cancer cells. In particular, the hit compound 3 was the most promising candidate and significantly inhibited the tumor growth of pancreatic cancer in tumor-bearing mice. The hit compound 3 represented a promising starting point for structural optimization in hit-to-lead development. This study shows that hit compound 3 provides a basis for the development of the treatment of cancer driven by KRASG12D.

Objective: The purpose of this study is to compare the dosimetric and biological evaluation differences between photon and proton radiation therapy. Methods: Thirty esophageal squamous cell carcinoma (ESCC) patients were generated for volumetric modulated arc therapy (VMAT) planning and intensity-modulated proton therapy (IMPT) planning to compare with intensity-modulated radiation therapy (IMRT) planning. According to dose-- volume histogram (DVH), dose--volume parameters of the plan target volume (PTV) and homogeneity index (HI), conformity index (CI), and gradient index (GI) were used to analyze the differences between the various plans. For the organs at risk (OARS), dosimetric parameters were compared. Tumor control probability (TCP) and normal tissue complication probability (NTCP) was also used to evaluate the biological effectiveness of different plannings. Results: CI, HI, and GI of IMPT planning were significantly superior in the three types of planning (p < 0.001, p < 0.001, and p < 0.001, respectively). Compared to IMRT and VMAT planning, IMPT planning improved the TCP (p<0.001, p<0.001, respectively). As for OARs, IMPT reduced the bilateral lung and heart accepted irradiation dose and volume. The dosimetric parameters, such as mean lung dose (MLD), mean heart dose (MHD), V5, V10, and V20, were significantly lower than IMRT or VMAT. IMPT afforded a lower maximum dose (Dmax) of the spinal cord than the other two-photon plans. What's more, the radiation pneumonia of the left lung, which was caused by IMPT, was lower than IMRT and VMAT. IMPT achieved the pericarditis probability of heart is only 1.73% ± 0.24%. For spinal cord myelitis necrosis, there was no significant difference between the three different technologies. Conclusion: Proton radiotherapy is an effective technology to relieve esophageal cancer, which could improve the TCP and spare the heart, lungs, and spinal cord. Our study provides a prediction of radiotherapy outcomes and further guides the individual treatment. [ABSTRACT FROM AUTHOR]

It was recently revealed that naturally occurring myricetin can inhibit ectonucleotidase ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which, in turn, can treat ischemic cardiac injury. However, due to myricetin's poor druggability, its further developments are relatively limited, which necessitates the discovery of novel ENPP1-inhibiting myricetin analogs as alternatives. In this study, the binding model of myricetin with ENPP1 was elucidated by molecular docking and molecular dynamics studies. Subsequently, virtual screening on the self-developed flavonoid natural product database (FNPD), led to the identification of two flavonoid glycosides (Cas No: 1397173-50-0 and 1169835-58-8), as potential ENPP1 inhibitors. Docking scores and MM/GBSA binding energies predicted that they might have higher inhibitory effects than myricetin. This study provides a strong foundation for the future development of ischemic cardiac injury drugs. [ABSTRACT FROM AUTHOR]

Chemical investigation of endophytic fungus Aspergillus fumigatus HQD24, isolated from the flower of Rhizophora mucronata led to the isolation of eight alkaloids, including pyripyropene A (1), 1,11-dideacetyl-pyripyropene A (2), pyripyropene E (3), chaetominine (4), tryptoquivaline J (5), fumitremorgin C (6), 1-acetyl-β-carboline (7), and nicotinic acid (8). Their structures were unambiguously elucidated on the basis of extensive spectroscopic data and comparison with the data of literature. Compound 2 was known as a synthetic product and isolated as a natural product for the first time. The immunosuppressive and cytotoxic activities of all isolated compounds were evaluated. [ABSTRACT FROM AUTHOR]

A method to synthesize novel tetradentate ligand and a new series of metal complexes comprising Co (II), Fe (II), Cu (II) and Zn (II) (1-4) using 3,5-dichlorosalicylaldehyde and trans 1,2-diaminocyclohexane is described. The structural features and mode of bonding exhibited by Schiff base have been characterized by spectral methods like UV-visible, FT-IR and ESI-MS. Schiff base ligand and (1-4) complexes have displayed superior antibacterial towards both Gram positive and Gram negative bacteria. The antioxidant studies have revealed significant free radical scavenging activity towards the free radical DPPH. Theoretical molecular docking studies are performed to elucidate the interactions of synthesized compounds with biomolecules. A model illustrating specific DNA-binding of synthesized compounds and groove binding mode of DNA interaction is evolved. Cu(II) complex (3) with more pronounced biological activity (antibacterial and antioxidant) has been subjected to cytotoxicity studies against MCF-7 breast cancer cell lines through MMT assay. Cu (II) complex have exhibited stronger anti-cancer activity in comparision to ligand in that way the synergistic effects of signifying Cu Schiff base complexes illustrate the higher inhibiting efficiency of 77.2% at 320 μg/mL. The proposed study, therefore discloses potentiality of the synthesized new Schiff base derived complexes as a prodrug for cancer treatment. [ABSTRACT FROM AUTHOR]

Maintaining a biological evaluation facility with reliability and acceptance is one of the critical issues in the field of medical device development. Establishing metrological traceability in the biological evaluation is a complex process when compared to the traceability in technical and industrial calibration and testing. In the development of medical devices, the risk of biocompatibility of biomaterials caused by chemical toxicity, physical characteristics like surface properties, presence of particulates, forces on surrounding tissue that might contribute to an unwanted tissue response, etc. has to be evaluated for their safe use. In a biological evaluation facility when reliability in test results and performance of the medical device are required for assuring patient safety, due considerations are to be given to testing and traceable calibration of associated equipment. Evidence for an established traceability chain through the use of metrological tools is one of the essential requirements for getting regulatory approval also. Therefore, regular conduct of calibrations and use of Reference Materials (RMs) in a biological evaluation facility is of utmost importance owing to the safety of patients. For the above reasons, this article will give a clear picture of the role of an accredited metrological system in the biological evaluation of materials and medical devices. [ABSTRACT FROM AUTHOR]

Serum and glucocorticoid-regulated kinase 1 (SGK1), as a serine threonine protein kinase of the AGC family, regulates different enzymes, transcription factors, ion channels, transporters, and cell proliferation and apoptosis. Inhibition of SGK1 is considered as a valuable approach for the treatment of various metabolic diseases. In this investigation, virtual screening methods, including pharmacophore models, Bayesian classifiers, and molecular docking, were combined to discover novel inhibitors of SGK1 from the database with 29,158 compounds. Then, the screened compounds were subjected to ADME/T, PAINS and drug-likeness analysis. Finally, 28 compounds with potential inhibition activity against SGK1 were selected for biological evaluation. The kinase inhibition activity test revealed that among these 28 hits, hit15 exhibited the highest inhibition activity against SGK1, which gave 44.79% inhibition rate at the concentration of 10 µM. In order to further investigate the interaction mechanism of hit15 and SGK1 at simulated physiological conditions, a molecular dynamics simulation was performed. The molecular dynamics simulation demonstrated that hit15 could bind to the active site of SGK1 and form stable interactions with key residues, such as Tyr178, ILE179, and VAL112. The binding free energy of the SGK1-hit15 was −48.90 kJ mol−1. Therefore, the identified hit15 with novel scaffold may be a promising lead compound for development of new SGK1 inhibitors for various diseases treatment. [ABSTRACT FROM AUTHOR]

Canola meal (CM) is used in all types of poultry feeds, however, because of its relatively low energy; its use in high energy broiler diets is restricted. No study has been conducted to evaluate the nutritional composition of CM derived from an Egyptian variety (Serw 4) grown in Egypt for poultry diets. The present study focused on the nutritional evaluation of Egyptian CM (ECM) compared with soybean meal (SBM). ECM contained lower crude protein (35.98 vs. 50.92%); more ether extract (EE) (10.35 vs. 1.69%), crude fiber (12.58 vs. 3.60), calcium (0.53 vs. 0.32%) and total phosphorus (1.16 vs. 0.73%) on dry matter basis. ECM contained more inhibitor contents like phytic acid (2.13 vs. 1.29%) as compared to SBM whereas as it had 22.47 µmol/gm glucosinolates while it was not determined for SBM. Compared with SBM, as fed basis ECM contained total essential amino acids (20.44 vs. 19.66%); lower essential amino acid index (51.32 vs. 54.55%). The first, second and third limiting amino acids of ECM were methionine, phenyl alanine and isoleucine, while those of SBM were valine, methionine and cysteine, respectively. The biological evaluation of ECM and SBM was investigated with force-fed adult cockerels assay. Comparable with SBM, ECM had a lower apparent and true metabolizable energy than that of SBM (1.75 vs. 2.28 Kcal/g) and (2.39 vs. 3.12 Kcal/g), respectively. The calculated protein replacement value of ECM from SBM in poultry diets was 92.22%. Compared with SBM, ECM had nearly similar true amino acids availability mean (109.56 vs. 109.06) and similar TAAA of most AA; therefore, it could be a good alternative protein source for SBM in poultry diets. Generally, the presence of these essential nutrients implies that CM could be utilized as a safe protein in poultry diets with no detrimental effect on growth performance. [ABSTRACT FROM AUTHOR]

Xanthine oxidase (XO) is an important enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid in the catabolism of purines in humans. This makes XO a well-recognized target in alleviating hyperuricemia. The present study adapted a structure-based drug discovery approach to develop potent and low-toxicity XO inhibitors with the chalcone skeleton. We introduced a carboxyl group and a hydroxyl group to the B ring and modified the A ring. 35 chalcone derivatives were designed and synthesized. All the 35 derivatives exhibited higher XO inhibition activities (IC 50  = 0.064-0.559 μM) compared with allopurinol (IC 50  = 2.588 μM). Their high affinity was attributed to strong hydrogen bond interactions formed between the introduced carboxyl and hydroxyl groups with key amino acid residues in XO. SAR analysis disclosed that carboxyl, hydroxyl, ethyl (12c), methylamino (12h), dimethylamino (12i), indolin (13k), and indol (13l) groups played important roles in improving the whole molecules' inhibition potency against XO. ADME predictions and cytotoxicity assays suggested their pharmacokinetic characteristics and biocompatibility were desirable. Additionally, 12c exhibited a significant hypouricemic effect on potassium oxonate-induced hyperuricemia rats after orally administrated at a dose range of 10-40 mg/kg, representing a promising anti-hyperuricemia potential for further optimization and development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

LSM-83177, a phenoxy acetic acid derivative, is a small molecule reported for its promising anti-tumor properties. Via inhibiting the interaction between MDM2 and p53, LSM-83177 can elevate the active p53 levels within cells, thereby promoting apoptosis and inhibiting tumor growth. Also, LSM-83177 has been shown to inhibit GST activity in colorectal cancer HT29 cells. In the current work, novel LSM-83177 hydrazone analogs 5a-f, 7a-b, 10a-e, and 13a-b have been designed according to the structure features of LSM-83177 and their binding mode in the active site of MDM2. The anti-cancer activity of the newly synthesized analogs is evaluated against the HT29 cell line. The most potent compounds, 7a and 10a, showed IC 50  = 12.48 and 10.44 µg/ml, respectively, when compared with Cisplatin (IC 50  = 11.32 µg/ml) as a reference drug. Compounds 7a and 10a were introduced for further inspection for p53-MDM2 protein-protein interaction, where they displayed IC 50 values of 3.65 and 11.08 µg/ml, respectively. Furthermore, hydrazones 7a and 10a increased the p-53 expression levels by 3.22- and 4.25-fold, respectively; in addition, they effectively reduced the GST expression levels in HT29 cancer cells with 0.56- and 0.30-fold increments in comparison to the untreated control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Claudin18.2 ( CLDN18.2), due to its high expression in various gastric cancer tissues, is considered an optimal target for antitumor drug molecules. In this study, we obtained the labeled compounds of [ 125 I]I-zolbetuximab using the Iodogen method. Under the optimum labeling conditions, the molar activity of [ 125 I]I-zolbetuximab was 1.75 × 10 2 GBq/μmol, and the labeling efficiency was more than 99%. The labeled compounds exhibited excellent in vitro stability in both phosphate buffer saline (PBS, pH = 7.4) and fetal bovine serum systems (FBS) (radiochemical purity >90% at 72 h). The uptake percentage of [ 125 I]I-zolbetuximab in MKN45-CLDN18.2 cells is 24.69 ± 0.84% after 6 h. The saturation binding assay and specificity assay further demonstrated the high specificity of [ 125 I]I-zolbetuximab for CLDN18.2. The long retention at the tumor site and rapid metabolic clearance at other organ sites of [ 125 I]I-zolbetuximab were observed in small-animal SPECT-CT imaging. The same trend was also observed in the biodistribution study. Due to the excellent targeting ability of zolbetuximab for CLDN18.2, [ 125 I]I-zolbetuximab exhibits strong specific binding and retention with cells and tumors highly expressing CLDN18.2. However, the balance between mAb's longer cycle time in vivo and targeting binding and retention ability should be intensively considered for using this kind of radiopharmaceutical in the diagnosis and treatment of CLDN18.2-positive gastric cancer.

As patients are dissatisfied with the excessive weight of Co-based knee femoral components, it is an urgent need to reduce their weight without compromising the excellent mechanical properties. In the present study, femoral components of knee with Ti6Al4V alloy (86 g) or Co–Cr alloy (192 g) were printed by selective laser melting (SLM). In order to improve the mechanical properties and biocompatibility of 3D-printed Ti6Al4V, TiN and TiCrN coating layers were deposited on the surface of SLM Ti6Al4V using arc ion plating (AIP) system. The surface characterizations were analyzed by scanning electron microscopy (SEM) equipped with energy dispersive spectrometer (EDS), X-ray diffraction (XRD), contact angle tensiometer, and contact profilometer. The wear property, hardness value and corrosion resistance in phosphate buffered saline (PBS) were also investigated through vickers hardness, sliding wear test, electrochemical impedance spectroscopy and potentiodynamic polarization. The antibacterial capability and biocompatibility were assessed with Staphylococcus aureus and mesenchymal stem cells (MSCs) in vitro. Results illustrated that, after coating SLM Ti6Al4V with thin TiN and TiCrN layers, the hardness, anti-wear performance and corrosion resistance of SLM Ti6Al4V were significantly improved and became comparable to SLM CoCr. The TiN and TiCrN coated SLM Ti6Al4V also showed moderate antibacterial ability, and excellent biocompatibility in comparation with SLM Ti6Al4V and SLM CoCr.

The objective of this study is to design and synthesize substituted η6-chromium(0) tricarbonyl metal complexes carrying o-carborane units as potential boron neutron capture therapy (BNCT) agents. In this study, 1,2-diphenyl-o-carborane (1) units were used as starting materials to generate biologically active species. We investigated how the structural changes of 1 substituted with chromium(0) tricarbonyl affect the biological properties, and 1-(Phenyl-η6-chromium(0) tricarbonyl)-2-phenyl-o-carborane (2) and 1,2-bis(phenyl-η6-chromium(0) tricarbonyl)-o-carborane (3) species were produced in moderate yields. The molecular structures of compounds 1–3 were identified and established by infrared (IR); 1H, 11B, and 13C nuclear magnetic resonance (NMR) and X-ray crystallography analyses. Crystal structures of 1,2-diphenyl-o-carborane and the corresponding chromium complexes 1, 2, and 3 were obtained. In an in vitro study using B16 and CT26 cancer cells containing the triphenyl-o-carboranyl chromium(0) complexes Ph3C2BCr2 and Ph3C2BCr3, which we reported previously, compounds 2 and 3 accumulated at higher levels than compounds Ph3C2BCr2 and Ph3C2BCr3. However, the phenylated o-carboranyl chromium complexes have been found to be more cytotoxic than p-boronophenylalanine (BPA).

The study was done to compare cell viability between ES-D3 and Balb/c 3T3 cells, and evaluate the difference in cell viability between these cell lines using denture-base lining materials for prosthetic dentistry. To compare the cytotoxicity, three acrylic and three silicone dental materials were used. The cell viability was examined by MTT and lactate dehydrogenase (LDH) methods. The cell viability immediately after malaxation or light irradiation was lower only for the acrylic materials in 3T3 cells, and for both silicone and acrylic materials in ES-D3 cells. However, the cell viability determined 24 h after malaxation or light irradiation by the MTT and LDH methods did not significantly differ between samples. It was observed that ES-D3 cells are more sensitive depending on the type of material. The results suggest that ES-D3 cells can be used as in vitro systems for conducting biosafety assessment to predict embryotoxicity. [ABSTRACT FROM AUTHOR]

Hyperlipidemia, an elevated level of cholesterol and/or triglycerides, has become a major public health problem worldwide. Although drugs intervention is effective in treating hyperlipidemia, most of them have adverse side effects. Peptides from natural plants with high anti-hyperlipidemic activity and a strong safety profile have emerged as promising candidates to prevent and ameliorate hyperlipidemia. This review summarizes the recent advances in plant-derived anti-hyperlipidemic peptides in terms of their sources, production, purification, identification, and activity evaluation. The focus is extended to their potential anti-hyperlipidemic mechanisms and structure-function relationships. Bioactive peptides derived from various plant sources, especially peptides containing hydrophobic and/or acidic amino acids, have shown remarkable effects in hyperlipidemic treatment. Their anti-hyperlipidemic effects are mediated by various mechanisms, including regulation of cholesterol metabolism and triglyceride metabolism, inhibition of inflammation-related metabolic syndrome, and modulation of the gut microbiota. Further evaluation of the stability, bioavailability, and clinical efficacy of these peptides is recommended. • Various plant-derived peptides have shown significant therapeutic potential for hyperlipidemia. • Most of plant-derived peptides exert anti-hyperlipidemic effects mainly by regulating TC metabolism and TG metabolism. • The peptides containing hydrophobic and/or acidic amino acids contribute to anti-hyperlipidemic activity. • Further evaluation of the stability, bioavailability, and clinical efficacy of anti-hyperlipidemic peptides are needed. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of the study is to characterize a biomedical magnesium alloy and highlighting the loss of mechanical integrity due to the sterilization method. Ideally, when using these alloys is to delay the onset of degradation so that the implant can support body loads and avoid toxicological effects due to the release of metal ions into the body. Methods Standardized procedures according to ASTM F-1264 and ISO-10993-5 were used, respecting detailed methodological controls to ensure accuracy and reproducibility of the results, this testing methodology is carried out in accordance with the monographs of the Pharmacopoeia for the approval of medical devices and obtaining a health registration. An intramedullary implant (IIM) manufactured in magnesium (Mg) WE43 can support loads of the body in the initial period of bone consolidation without compromising the integrity of the fractured area. A system with these characteristics would improve morbidity and health costs by avoiding secondary surgical interventions. Results As a property, the fatigue resistance of Mg in aggressive environments such as the body environment undergoes progressive degradation, however, the autoclave sterilization method drastically affects fatigue resistance, as demonstrated in tests carried out under in vitro conditions. Coupled with this phenomenon, the relatively poor biocompatibility of Mg WE43 alloys has limited applications where they can be used due to low acceptance rates from agencies such as the FDA. However, Mg alloy with elements such as yttrium and rare earth elements (REEs) have been shown to delay biodegradation depending on the method of sterilization and the physiological solution used. With different sterilization techniques, it may be possible to keep toxicological effects to a minimum while still ensuring a balance between the integrity of fractured bone and implant degradation time. Therefore, the evaluation of fatigue resistance of WE43 specimens sterilized and tested in immersion conditions (enriched Hank’s solution) and according to ASTM F-1264, along with the morphological, crystallinity, and biocompatibility characterization of the WE43 alloy allows for a comprehensive evaluation of the mechanical and biological properties of WE43. Conclusions These results will support decision-making to generate a change in the current perspective of biomaterials utilized in medical devices (MDs), to be considered by manufacturers and health regulatory agencies. An implant manufactured in WE43 alloy can be used as an intramedullary implant, considering keeping elements such as yttrium-REEs below as specified in its designation and with the help of a coating that allows increasing the life of the implant in vivo.

ISO 10993-1:2018 describes evaluating the biocompatibility profile of a medical device from a risk-based approach. This standard details the battery of information that should be considered within the assessment of a device, including raw material composition data, manufacturing processes, and endpoint testing. The ISO 10993/18562 series requires worst-case assumptions and exposure scenarios to be used in the evaluation, which may result in an over-estimation of patient safety risk. Currently, biocompatibility assessments evaluate each data set independently, and the consequence of this individualized assessment of exaggerated inputs is potential false alarms regarding patient safety. To evaluate these safety concerns, the ISO standards indicate that professional judgement should be used to estimate patient risk but does not provide guidance on incorporating a holistic review of the data into the risk assessment. Recalibrating these worst-case data to evaluate them in a weight-of-evidence (WoE) approach may provide a more realistic data set to determine actual patient risk. This proposed WoE framework combines understanding data applicability with a method for gauging the strength of data that can provide additional support for the final safety conclusion. Using a WoE framework will allow risk assessors to contextualize the data and utilize it to comprehensively estimate patient safety. • ISO 10993 requires conservative assumptions leading to over-estimation of risk. • Biological evaluations of medical devices should include holistic data review. • Weight-of-Evidence framework provides guidance on integrative data assessment. • Qualitative scoring system gauges strength of data profile and final risk conclusion. [ABSTRACT FROM AUTHOR]

Two series of novel sophoridine derivatives were designed, synthesized, and evaluated for their anti-mosquito activity. SOP-2g, SOP-2q, and SOP-2r exhibited potential larvicidal activity against Aedes albopictus larva with LC50 values of 330.98, 430.53, and 411.09 ppm, respectively. Analysis of structure–activity relationships indicated that the oxime ester group was beneficial for improving the larvicidal biological activity, whereas the long-chain aliphatic group and fused-ring group were introduced. Furthermore, the larvicidal mechanism was also investigated based on the inhibition assay of acetylcholinesterase (AChE) and the morphological observation of dead larva treated with derivatives. Results indicated that the AChE inhibitory activity of the preferred three derivatives were 63.16%, 46.67%, and 35.11%, respectively, at 250 ppm concentration. Additionally, morphological evidence demonstrated that SOP-2q and SOP-2r induced changes in the larva’s intestinal cavity, caudal gill, and tail, thereby displaying larvicidal action against Ae. albopictus together with AChE inhibition. Therefore, this study implied that sophoridine and its novel derivatives could be used to control the population of mosquito larva, which may also be effective alkaloids to reduce the mosquito population density.

The discovery and development of new drugs are extremely long and costly processes. Recent progress in artificial intelligence has made a positive impact on the drug development pipeline. Numerous challenges have been addressed with the growing exploitation of drug-related data and the advancement of deep learning technology. Several model frameworks have been proposed to enhance the performance of deep learning algorithms in molecular design. However, only a few have had an immediate impact on drug development since computational results may not be confirmed experimentally. This systematic review aims to summarize the different deep learning architectures used in the drug discovery process and are validated with further in vivo experiments. For each presented study, the proposed molecule or peptide that has been generated or identified by the deep learning model has been biologically evaluated in animal models. These state-of-the-art studies highlight that even if artificial intelligence in drug discovery is still in its infancy, it has great potential to accelerate the drug discovery cycle, reduce the required costs, and contribute to the integration of the 3R (Replacement, Reduction, Refinement) principles. Out of all the reviewed scientific articles, seven algorithms were identified: recurrent neural networks, specifically, long short-term memory (LSTM-RNNs), Autoencoders (AEs) and their Wasserstein Autoencoders (WAEs) and Variational Autoencoders (VAEs) variants; Convolutional Neural Networks (CNNs); Direct Message Passing Neural Networks (D-MPNNs); and Multitask Deep Neural Networks (MTDNNs). LSTM-RNNs were the most used architectures with molecules or peptide sequences as inputs.

PLK-1 (Polo-like kinase-1) plays an essential role in cytokinesis, and its aberrant expression is considered to be keenly associated with a wide range of cancers. It has been selected as an appealing target and small-molecule inhibitors have been developed and studied in clinical trials. Unfortunately, most have been declared as failures due to the poor therapeutic response and off-target toxicity. In the present study, a novel potent PLK-1 inhibitor, compound 7a, was designed and synthetized. 1H NMR, 13C NMR, 19F NMR and mass spectrum were comprehensively used for the compound characterization. The compound exhibited higher potency against PLK-1 kinase, HCT-116 and NCI-H2030 cell lines than the positive control. Molecular docking indicated that the binding mode that the ATP binding site of PLK-1 was occupied by the compound. Then, a UHPLC-MS/MS method was established and validated to explore the pharmacokinetic behavior of the drug candidate. The method had good selectivity, high sensitivity and wide linearity. The exposure increased linearly with the dose, but the oral bioavailability was not satisfactory enough. Then, the metabolism was studied using liver microsomes by UHPLC-Q-Orbitrap/HRMS. Our research first studied the pharmacokinetic metabolic characteristics of 7a and may serve as a novel lead compound for the development of PLK-1 inhibitors.

This work focuses on tracking ulcerative colitis in mice. High labeling yield and radiochemical purity were achieved for the formation of a [125/131I]balsalazide radiotracer at optimum conditions of oxidizing agent content (chloramines‐T [Ch‐T], 75 μg), substrate amount (100 μg), pH of reaction mixture (6), reaction time (30 min), and temperature (37°C), using radioactive iodine‐125 (200–450 MBq). The radiolabeled compound, [125/131I]balsalazide, was stable in serum and saline solution during 24 h. Balsalazide is acting as a peroxisome proliferator‐activated receptor (PPARγ). Biodistribution studies were carried in normal and ulcerated colon mice. High uptake of 75 ± 1.90% injected dose/g organ (ID/g) observed in ulcerated mice confirmed the suitability of [131I]balsalazide as a novel radiotracer for ulcerative colitis imaging in mice. [ABSTRACT FROM AUTHOR]

New Schiff base transition metal complexes derived from 3-ethoxy-2-hydroxy-benzaldehyde and aniline were characterized by magnetic susceptibility measurements, molar conductance, MS, FT-IR, ¹H-NMR, 13C-NMR, Absorbance and EPR spectra. The spectral evidences clearly showed that all the metal chelates distorted octahedral geometry except Zn(II) complex which exist square planar geometry. Electron Spin Resonance (ESR) spectrum of [CuL] complex was coinciding with proposed geometries and other reported complexes. All the synthesized compounds were studied for anticancer studies by MTT method using Hela cells. From anticancer activities, the observed IC50 values of synthesized complexes are significantly higher than standard Cis-platin. The cytotoxicity of the tested compounds against the Hela cell line pursued their order Co(II) > Cu(II) > Zn(II) > ligand. Among them, Co(II) complex showed higher cytotoxic activity than other complexes and Schiff base. [ABSTRACT FROM AUTHOR]

The current study was carried out to evaluate eco-friendly extracts of an invasive weed; Eichhornia crassipes (Mart.) Solms (Pontederiaceae) for controlling Agrotis ipsilon (Hufn.) (Lepidotera: Noctuidae). The insecticidal and biological activities of the whole plant extracts with different polarity solvents (petroleum ether, acetone, and absolute ethanol) were investigated. The extracts were evaluated against the 2nd larval instars of A. ipsilon. The results revealed that acetone fraction extract was the most effective extract with the lowest LC50 value (240 mg/L). The larval mortality percentage increased by elevating concentrations of all tested extracts. Pupation and adult emergence percentages were inversely proportional with the concentration of all tested extracts. There was a disturbance in both the adult malformation and sex ratios. Furthermore, the spectrophotometric testing of the most promising extracts (acetone and ethanol fractions) on some biochemical parameters (total body metabolites, acid and alkaline phosphatases, aminotransferase activities, and kidney function) in the serum of albino rats showed non-toxic effects on mammals. Therefore, acetone and ethanol fraction extracts of E. crassipes were considered promising eco-friendly insecticidal alternatives in (Integrated Pest Management) IPM programs to control A. ipsilon worldwide. [ABSTRACT FROM AUTHOR]

In present work we synthesized novel series of thiazole derivatives of N-((2-chlorophenyl)diphenylmethyl)-4-phenylthiazol-2-amine in the presence of dichloromethane and triethylamine in good yield. The different studies indicate that newly synthesized compounds possess moderate to good biological activities. The title compounds have been synthesized with several structural variations. Biological evaluation of all the synthesized compounds has been carried out in vitro for their antibacterial and antifungal efficacy against various bacterial and fungal strains. The structure of synthesized compounds were characterized by their spectral (IR, 1H NMR and Mass) data. [ABSTRACT FROM AUTHOR]

Nowadays there is an increasing interest in the use of honey in the traditional Mediterranean diet, due to its high quality of sugar content as well as its strong antioxidant and antibacterial properties. Thus, the detailed knowledge of the chemical composition and bioactivities of honey is of great importance. In this study, the chemical characterization and the authentication of the aromatic profile, the total phenolic content, the antimicrobial evaluation, and the pollinic spectrum of Greek strawberry-tree (Arbutus unedo L.) honey were studied. Typification of Arbutus honey sample was based on its pollinic spectrum exerted an approx. 23% on Ericaceae pollen (expressed to Arbutus unedo pollen). The studied sample was analysed through GC-MS and among the volatile substances: benzene derivatives (dimethyl, trimethyl, and tetramethyl), β-isophorone, α-isophorone, 4-oxoisophorone, dihydrooxophorone, and 2-Hydroxy-4-oxoisophorone were detected, together with homogentistic acid (HGA) and 5-hydroxymethylfurfural (HMF), known as an essential parameter of freshness and of good quality of commercial honeys. The chemical markers of such European honeys, unedone and 2-cis-4-trans-abscisic acid (c-t-ABA), have been isolated and structurally determined by spectral means. Furthermore, the sample exhibited a high total phenolic content and an interesting antimicrobial activity against human pathogenic microorganisms, suggesting that the consumption of Greek strawberry tree honey could have beneficial effects. [ABSTRACT FROM AUTHOR]

Prominent in the current stage of drug development, antiviral compounds can be efficiently prepared through cycloaddition reactions. This review reports the use of 1,3-dipolar cycloaddition reactions of selected 1,3- dipoles, in particular azides, in the light of their application for the preparation of key intermediates in the design and synthesis of compounds that were tested for their antiviral activities against a variety of viruses. The products obtained from these pericyclic reaction approaches were tested for their activities in terms of blocking the virus replication and the relevant biological data are highlighted. [ABSTRACT FROM AUTHOR]

Protein tyrosine phosphatase 1B (PTP1B) is a member of the phosphotyrosine phosphatase family and plays an important role in the signal transduction of diabetes. Inhibition of PTP1B activity can increase insulin sensitivity and reduce blood sugar levels. Therefore, it is urgent to find compounds with novel structures that can inhibit PTP1B. This study designed imidazolidine-2,4-dione derivatives through the computer-aided drug design (CADD) strategy, and the Comp#10 showed outstanding inhibitory ability. (IC 50 = 2.07 μM) and selectivity. The inhibitory mechanism at molecular level of Comp#10 on PTP1B was studied by molecular dynamics simulation. The results show that the catalytic region of PTP1B protein is more stable, which makes the catalytic sites unsuitable for exposure. Interestingly, the most obvious changes in the interaction between residues in the P-loop region (such as: His214, Cys215, and Ser216). In short, this study reported for the first time that imidazolidine-2,4-dione derivatives as novel PTP1B inhibitors had good inhibitory activity and selectivity, providing new ideas for the development of small molecule PTP1B inhibitors. [Display omitted] • A series of imidazolidine-2,4-dione derivatives were designed on the basis of CADD. • 15 new imidazolidine-2,4-dione molecules were synthesized and characterized. • 9 compounds can inhibit the activity of PTP1B protein. It is worth noting that Comp#10 has the highest ability to PTP1B protein (IC50 = 2.07 μM). • The inhibitory mechanism at molecular level of Comp#10 on PTP1B was studied by molecular dynamics simulation. [ABSTRACT FROM AUTHOR]

Abstract Quality consistency is one of the basic attributes of medicines, but it is also a difficult problem that natural medicines and their preparations must face. The complex chemical composition and comprehensive pharmacological action of natural medicines make it difficult to simply apply the commonly used evaluation methods in chemical drugs. It is thus urgent to explore the novel evaluation methods suitable for the characteristics of natural medicines. With the rapid development of analytical techniques and the deepening understanding of the quality of natural herbs, increasing numbers of researchers have proposed many new ideas and technologies. This review mainly focuses on the basic principles, technical characteristics and application examples of the chemical evaluation, biological evaluation methods and their combination in quality consistency evaluation of natural herbs. On the bases of chemical evaluation and clinical efficacy, new methods reflecting their pharmacodynamic mechanism and safety characteristics will be developed, and gradually towards accurate quality control, to achieve the goal of quality consistency. We hope that this manuscript can provide new ideas and technical references for the quality consistency of natural drugs and their preparations, thus better guarantee their clinical efficacy and safety, and better promote industrial development.

In order to achieve smart biomedical micro/nanomaterials, promote interaction with biomolecules, improve osteogenic/chondrogenic differentiation, exhibit better dispersion in bone implants and ultimately maximize functionality, we innovatively and successfully designed and synthesized polymer PBLG-modified GdPO4·H2O nanobunches by hydroxylation, silylation and glutamylation processes. The effects of different feeding ratios on the surface coating of GdPO4·H2O with Si-OH, the grafting γ-aminopropyltriethoxysilane (APS) and the in situ ring-opening polymerization reaction of poly(g-benzyl-L-glutamate) (PBLG) were investigated, and the physical and chemical properties were characterized in detail. When GdPO4·H2O@SiO2–APS:NCA = 4:1, the PBLG-g-GdPO4·H2O grafting rate was 5.93%, with good stability and dispersion in degradable polymeric materials. However, the MRI imaging signal was sequentially weakened as the modification process proceeded. Despite this, the biological effects had surprising findings. All the modifiers at appropriate concentrations were biocompatible and biologically active and the biomacromolecules of COL I and COL II in particular were expressed at least 3 times higher in GdPO4·H2O@SiO2 compared to the PLGA. This indicates that the appropriate surface modification and functionalization of gadolinium-containing micro/nanomaterials can promote interaction with cells and encourage bone regeneration by regulating biomacromolecules and can be used in the field of biomedical materials.

Numerous food organizations have identified excessive calorie consumption and accompanying ailments as significant health risks associated with high sugar consumption. Administering stevioside (ST), sucralose (SU), and the two synergically (SU+ST) affected normal rats’ weight gain. In the current study, SU showed the highest undesired effect. Indeed, administering the three treatments to diabetic rats (DR) did not improve the rats’ weight gain. Although, insulin injection synergically with the treatments improved the weight gain, as recorded after three weeks. The best-improving rate was observed in the ST group. After the administration of ST and ST+SU to the DR, the blood glucose level (GL) was positively affected, with SU having no effects on reducing the GL. A considerable reduction in serum insulin (SIL) was noted in the DR+SU group. On the contrary, ST did not negatively affect the SIL, rather an improvement was recorded. In addition, giving SU did not significantly affect the ALT level in the DR or normal rats (NR). A significant improvement in total bilirubin (TBILI) was observed when insulin was injected with ST or SU in DR groups. Further, triglycerides (TG) after administering ST, SU, or ST+SU to NR had no significant difference compared to the control group (NR). Although, the three treatments markedly but not significantly lowered TG in the DR. For total cholesterol (CHO), both DR and NR had no significant effect after the three treatments. No histopathological alterations were recorded in the NR group. Diffuse and severe atrophy of the islands of Langerhans due to depletion of their cells and mild papillary hyperplasia of the pancreatic ducts were represented by a slightly folded ductal basement membrane and newly formed ductules in STZ-DR. Simultaneous atrophy and absence of the cells of islands of Langerhans besides ductal hyperplasia were evident in DR+SU. Hyperplastic ductal epithelium and atrophic Langerhans cells were seen in DR+SU+In. Degeneration and mild atrophy were observed in the islands of Langerhans structures. There was essentially no noticeable change after utilizing ST. A slight shrinkage of the Langerhans’ islets was detected in DR+ST. In DR+ST+In, no histopathological alterations in the islands of Langerhans were recorded. Congestion in the stromal blood vessels associated with degenerative and necrotic changes in the cells of the islands of Langerhans in DR+SU+ST was observed. In NR+SU, congestion of the blood vessels associated with mild atrophy in the islands of Langerhans and dilatation in stromal blood vessels was noticed. In conclusion, ST is safe, and SU should be taken cautiously, such as mixing with ST and/or taken at a very low concentration to avoid its drastic effect on the human body.

Natural extracts have been and continue to be used to treat a wide range of medical conditions, from infectious diseases to cancer, based on their convenience and therapeutic potential. Natural products derived from microbes, plants, and animals offer a broad variety of molecules and chemical compounds. Natural products are not only one of the most important sources for innovative drug development for animal and human health, but they are also an inspiration for synthetic biology and chemistry scientists towards the discovery of new bioactive compounds and pharmaceuticals. This is particularly relevant in the current context, where antimicrobial resistance has risen as a global health problem. Thus, efforts are being directed toward studying natural compounds’ chemical composition and bioactive potential to generate drugs with better efficacy and lower toxicity than existing molecules. Currently, a wide range of methodologies are used to analyze the in vitro activity of natural extracts to determine their suitability as antimicrobial agents. Despite traditional technologies being the most employed, technological advances have contributed to the implementation of methods able to circumvent issues related to analysis capacity, time, sensitivity, and reproducibility. This review produces an updated analysis of the conventional and current methods to evaluate the antimicrobial activity of natural compounds.

Nowadays, functional and entirely natural dressing treated with biological active polymers is a required alternative to treat chronic or acute wounds. First, a Suaeda fruticosa polysaccharide (SFP) was extracted and its pectin-like polysaccharide structure was confirmed via infrared spectroscopy (FT-IR), steric exclusion chromatography, gas chromatography-mass spectrometry (GC–MS) and chemical composition analyses. Then, a new natural biopolymer-based chitosan and SFP extract was synthesized and grafted to cellulosic wound textile dressing. Different parameters of grafting such as temperature and curing time were studied and further optimized. The functionalized dressings were characterized by infrared via attenuated total reflectance mode, SEM, and mechanical analysis. The swelling behavior analysis showed a significant improvement of the hydrophilicity after grafting which is a required property for enhanced healing efficiency. Biological analysis was achieved via viability and kinetic cell adhesion tests, using epithelial HepG2 cells. A bacteriological evaluation of functionalized dressings against gram positive and negative bacteria culture strains was also performed. The new functional cellulosic wound dressing revealed efficient and promising microbiological performance able to treat chronic and acute wounds. [ABSTRACT FROM AUTHOR]

This work covers the synthesis and characterization of a new Azo-Schiff base ligand and it,s binuclear metal complexes. The ligand namely 4-[2-(4-chloro phenyl) diazen-1-yl]-2-[({4-[(E)-({5-[2-(4-chloro phenyl) diazen-1-yl]-2-hydroxy phenyl} methylidene) amino] phenyl} imino) methyl] phenol prepared from the condensation reaction of 5-((4-Chloro phenyl) diazenyl)-2-hydroxy benzaldehyde with p-Phenylene diamine in (2:1) mole ratio. A series of a binuclear metal complexes were prepared from the reaction of the ligand with the metal chloride of Cd(II), Ni(II), Cr(II), Cu(II), Mn(II), Co(II) and Zn(II) with a molar ratio of 1:2 (L:M) using EtOH as the reaction medium . The ligand and its complexes were characterized using elemental analysis, melting point, metal content, magnetic susceptibility, FT-IR, UV-vis and ¹H -NMR spectroscopy and molar conductance which showed that all complexes were non-electrolyte. The characterization data revealed the isolation of a six coordinate binuclear complexes with the general formule; [M2(H2L)(Cl)2(H2O)4] were [M = Cd(II) and Cu(II) ]. [M2(H2L)(Cl)2(H2O)6] were [M = Zn(II) and Mn(II)]. The suggested geometry for six-coordinate is a distorted octahedral arrangement. The prepared compounds were screened against. G-positive and G-negative bacterial strains and fungi. The obtained data Confirmed that all compounds have an anti-microbial activity except Mn(II) complex. [ABSTRACT FROM AUTHOR]

Epoxyeicosatrienoic acids (EETs) are produced by the effect of cytochrome P 450 (CYP) on arachidonic acid (AA), and have a beneficial performance to renal and cardiovascular systems. In recent decades, many new pharmacological agents have been developed to inhibit the soluble epoxide hydrolase (sEH) and consequently, maintain EETs serum level in high concentrations. In the present study, a series of novel amide derivatives were designed and investigated with a 1,2,3-triazole ring as a secondary pharmacophore against sEH enzyme. Based on docking studies, these novel structures were suitably located in the active site of the enzyme. All final compounds showed satisfactory inhibitory activity against sEH with proper IC50 values (0.9–55.5 nM). Compound 5l, as the most potent compound, could be a valuable structure for further investigation. According to in silico ADME calculations, these novel compounds could be formulated as orally active agents. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to show the advantages of each stereotactic radiosurgery (SRS) treatment option for single small brain metastasis among Gamma Knife (GK), Cone-based VMAT (Cone-VMAT), and MLC-based CRT (MLC-CRT) plans. Materials and Methods: GK, Cone-VMAT, and MLC-CRT SRS plans were retrospectively generated for 11 patients with single small brain metastasis whose volume of gross tumor volume (GTV) ranged from 0.18 to 0.76 cc (median volume 0.60 cc). Dosimetric parameters, treatment efficiency, and biological parameters of the three techniques were compared and evaluated. The metric variation with the planning target volume (PTV) was also studied. Results: The conformity index (CI) was similar in GK and MLC-CRT plans, higher than Cone-VMAT. Cone-VMAT achieved comparable volume covered by 12 Gy (V12) and gradient index (GI) as GK, lower than MLC-CRT. The heterogeneity index (HI) of GK, Cone-VMAT, and MLC-CRT decreased sequentially. GK gave the lowest volume covered by 3 Gy (V3) and 6 Gy (V6), while MLC-CRT got the highest. The beam-on time and treatment time of GK, Cone-VMAT, and MLC-CRT decreased in turn. Tumor control probability (TCP) of all three SRS plans was greater than 98%, and normal tissue complication probability (NTCP) of all organs at risk (OARs) was below 0.01%. GK and Cone-VMAT resulted in superior TCP and NTCP of the normal brain tissue than MLC-CRT. The relative value of Cone-VMAT and GK for all metrics hardly changed with the target volume. Except for the unchanged HI and TCP, the other results of MLC-CRT with respect to GK improved as the target volume increased. MLC-CRT could produce higher CI than GK and Cone-VMAT when the target volume increased above 2 and 1.44 cc, respectively. Conclusion: For single small brain metastases, Cone-VMAT may be used as an alternative to GK-free centers. In addition to the advantage of short treatment time, MLC-CRT showed superiority in CI as the target volume increased. Treatment centers can choose appropriate SRS technique on a case-by-case basis according to institutional conditions and patients' individual needs. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Dysregulated HGF/c‐Met signalling has been associated with many human cancers, poor clinical outcomes, and even resistance acquisition to some approved targeted therapies. As such, c‐Met kinase has emerged as an attractive target for anticancer drug discovery. Herein, a series of 6,7‐disubstitued‐4‐(2‐fluorophenoxy)quinoline derivatives bearing α‐acyloxycarboxamide moiety were designed, synthesized via Passerini reaction as the key step, and evaluated for their in vitro biological activities against c‐Met kinase and five selected cancer cell lines. The preliminary structure‐activity relationship demonstrated that α‐acyloxycarboxamide as the 5‐atom linker maintained the potent antitumor potency. Among these compounds, compound 25s (c‐Met IC50 = 4.06 nmol/L) was identified as the most promising lead compound and displayed the most potent antiproliferative activities against A549, HT‐29 and MDA‐MB‐231 cell lines with IC50 of 0.39, 0.20, and 0.58 μmol/L, which were 1.3‐, 1.4‐ and 1.2‐fold superior to foretinib, respectively. The further studies indicated that compound 25s can induce apoptosis of A549 cells and arrest efficiently the cell cycle distribution in G2/M phase of A549 cells. Moreover, compound 25s can also inhibit c‐Met phosphorylation in A549 cells by a dose‐dependent manner. Collectively, these results indicated that compound 25s could be a potential anticancer lead compound deserving for further development. [ABSTRACT FROM AUTHOR]

The heterocyclic 3H‐pyrrolo[2,3‐c]quinoline system and its closely related natural products, the marinoquinolines, have been attracting considerable attention in recent years in view of its interesting chemistry and diverse biological activities. Known since 1924, only in 2006 were the 3H‐pyrrolo[2,3‐c]quinolines associated with the first marinoquinolines isolated from natural sources. Their architecture and biological activities such as antiplasmodial, anti‐proliferative, anti‐bacterial, antifungal, phosphodiesterase and AChE inhibitors, and as ion‐sensing have stimulated the development of new strategies to obtain the natural marinoquinolines and new 3H‐pyrrolo[2,3‐c]quinoline derivatives. This review details the recent synthesis and biological evaluation of natural and unnatural marinoquinolines and its 3H‐pyrrolo[2,3‐c]quinoline core. [ABSTRACT FROM AUTHOR]

ObjectivesThis study aimed to show the advantages of each stereotactic radiosurgery (SRS) treatment option for single small brain metastasis among Gamma Knife (GK), Cone-based VMAT (Cone-VMAT), and MLC-based CRT (MLC-CRT) plans.Materials and MethodsGK, Cone-VMAT, and MLC-CRT SRS plans were retrospectively generated for 11 patients with single small brain metastasis whose volume of gross tumor volume (GTV) ranged from 0.18 to 0.76 cc (median volume 0.60 cc). Dosimetric parameters, treatment efficiency, and biological parameters of the three techniques were compared and evaluated. The metric variation with the planning target volume (PTV) was also studied.ResultsThe conformity index (CI) was similar in GK and MLC-CRT plans, higher than Cone-VMAT. Cone-VMAT achieved comparable volume covered by 12 Gy (V12) and gradient index (GI) as GK, lower than MLC-CRT. The heterogeneity index (HI) of GK, Cone-VMAT, and MLC-CRT decreased sequentially. GK gave the lowest volume covered by 3 Gy (V3) and 6 Gy (V6), while MLC-CRT got the highest. The beam-on time and treatment time of GK, Cone-VMAT, and MLC-CRT decreased in turn. Tumor control probability (TCP) of all three SRS plans was greater than 98%, and normal tissue complication probability (NTCP) of all organs at risk (OARs) was below 0.01%. GK and Cone-VMAT resulted in superior TCP and NTCP of the normal brain tissue than MLC-CRT. The relative value of Cone-VMAT and GK for all metrics hardly changed with the target volume. Except for the unchanged HI and TCP, the other results of MLC-CRT with respect to GK improved as the target volume increased. MLC-CRT could produce higher CI than GK and Cone-VMAT when the target volume increased above 2 and 1.44 cc, respectively.ConclusionFor single small brain metastases, Cone-VMAT may be used as an alternative to GK-free centers. In addition to the advantage of short treatment time, MLC-CRT showed superiority in CI as the target volume increased. Treatment centers can choose appropriate SRS technique on a case-by-case basis according to institutional conditions and patients’ individual needs.

It was recently revealed that naturally occurring myricetin can inhibit ectonucleotidase ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which, in turn, can treat ischemic cardiac injury. However, due to myricetin’s poor druggability, its further developments are relatively limited, which necessitates the discovery of novel ENPP1-inhibiting myricetin analogs as alternatives. In this study, the binding model of myricetin with ENPP1 was elucidated by molecular docking and molecular dynamics studies. Subsequently, virtual screening on the self-developed flavonoid natural product database (FNPD), led to the identification of two flavonoid glycosides (Cas No: 1397173-50-0 and 1169835-58-8), as potential ENPP1 inhibitors. Docking scores and MM/GBSA binding energies predicted that they might have higher inhibitory effects than myricetin. This study provides a strong foundation for the future development of ischemic cardiac injury drugs.