Facile Synthesis of Some Coumarin Derivatives and Their Cytotoxicity through VEGFR2 and Topoisomerase II Inhibition.

Novel semisynthetic coumarin derivatives were synthesized to be developed as chemotherapeutic anticancer agents through topoisomerase II, VEGFR2 inhibition that leads to apoptotic cancer cell death. The coumarin amino acids and dipeptides derivatives were prepared by the reaction of coumarin-3-carboxylic acid with amino acid methyl esters following the N,N-dicyclohexylcarbodiimide (DCC) method and 1-hydroxy-benzotriazole (HOBt), as coupling reagents. The synthesized compounds were screened towards VEGFR2, and topoisomerase IIα proteins to highlight their binding affinities and virtual mechanism of binding. Interestingly, compounds 4k (Tyr) and 6c (ß-Ala-L-Met) shared the activity towards the three proteins by forming the same interactions with the key amino acids, such as the co-crystallized ligands. Both compounds 4k and 6c exhibited potent cytotoxic activities against MCF-7 cells with IC50 values of 4.98 and 5.85 µM, respectively causing cell death by 97.82 and 97.35%, respectively. Validating the molecular docking studies, both compounds demonstrated promising VEGFR-2 inhibition with IC50 values of 23.6 and 34.2 µM, compared to Sorafenib (30 µM) and topoisomerase-II inhibition with IC50 values of 4.1 and 8.6 µM compared to Doxorubicin (9.65 µM). Hence, these two promising compounds could be further tested as effective and selective target-oriented active agents against cancer.

Synthesis of M-Ag3PO4, (M = Se, Ag, Ta) Nanoparticles and Their Antibacterial and Cytotoxicity Study.

Silver Phosphate, Ag3PO4, being a highly capable clinical molecule, an ultrasonic method was employed to synthesize the M-Ag3PO4, (M = Se, Ag, Ta) nanoparticles which were evaluated for antibacterial and cytotoxicity activities post-characterization. Escherichia coli and Staphylococcus aureus were used for antibacterial testing and the effects of sonication on bacterial growth with sub-MIC values of M-Ag3PO4 nanoparticles were examined. The effect of M-Ag3PO4 nanoparticles on human colorectal carcinoma cells (HCT-116) and human cervical carcinoma cells (HeLa cells) was examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay and DAPI (4',6-diamidino-2-phenylindole) staining. Additionally, we analyzed the effect of nanoparticles on normal and non-cancerous human embryonic kidney cells (HEK-293). Ag-Ag3PO4 exhibited enhanced antibacterial activity followed by Ta-Ag3PO4, Ag3PO4, and Se-Ag3PO4 nanoparticles against E. coli. Whereas the order of antibacterial activity against Staphylococcus aureus was Ag3PO4 > Ag-Ag3PO4 > Ta-Ag3PO4 > Se-Ag3PO4, respectively. Percentage inhibition of E. coli was 98.27, 74.38, 100, and 94.2%, while percentage inhibition of S. aureus was 25.53, 80.28, 99.36, and 20.22% after treatment with Ag3PO4, Se-Ag3PO4, Ag-Ag3PO4, and Ta-Ag3PO4, respectively. The MTT assay shows a significant decline in the cell viability after treating with M-Ag3PO4 nanoparticles. The IC50 values for Ag3PO4, Se-Ag3PO4, Ag-Ag3PO4, and Ta-Ag3PO4 on HCT-116 were 39.44, 28.33, 60.24, 58.34 µg/mL; whereas for HeLa cells, they were 65.25, 61.27, 75.52, 72.82 µg/mL, respectively. M-Ag3PO4 nanoparticles did not inhibit HEK-293 cells. Apoptotic assay revealed that the numbers of DAPI stained cells were significantly lower in the M-Ag3PO4-treated cells versus control.

A well-defined S-g-C3N4/Cu-NiS heterojunction interface towards enhanced spatial charge separation with excellent photocatalytic ability: synergetic effect, kinetics, antibacterial activity, and mechanism insights.

A well-defined heterojunction among two dissimilar semiconductors exhibited enhanced photocatalytic performance owing to its capability for boosting the photoinduced electron/hole pair transportation. Therefore, designing and developing such heterojunctions using diverse semiconductor-based materials to enhance the photocatalytic ability employing various approaches have gained research attention. For this objective, g-C3N4 is considered as a potential photocatalytic material for organic dye degradation; however, the rapid recombination rate of photoinduced charge carriers restricts the widespread applications of g-C3N4. Henceforth, in the current study, we constructed a heterojunction of S-g-C3N4/Cu-NiS (SCN/CNS) two-dimensional/one-dimensional (2D/1D) binary nanocomposites (NCs) by a self-assembly approach. XRD results confirm the construction of 22% SCN/7CNS binary NCs. TEM analysis demonstrates that binary NCs comprise Cu-NiS nanorods (NRs) integrated with nanosheets (NSs) such as the morphology of SCN. The observed bandgap value of SCN is 2.69 eV; nevertheless, the SCN/CNS binary NCs shift the bandgap to 2.63 eV. Photoluminescence spectral analysis displays that the electron-hole pair recombination rate in the SCN/CNS binary NCs is excellently reduced owing to the construction of the well-defined heterojunction. The photoelectrochemical observations illustrate that SCN/CNS binary NCs improve the photocurrent to ∼0.66 mA and efficiently suppress the electron-hole pairs when compared with that of undoped NiS, CNS and SCN. Therefore, the 22% SCN/7CNS binary NCs efficiently improved methylene blue (MB) degradation to 99% for 32 min under visible light irradiation.

Synthesis, α-amylase and α-glucosidase inhibition and molecular docking studies of indazole derivatives.

Herein, we report the synthesis and inhibitory potential of indazole (Methyl 1H-indazole-4-carboxylate) derivatives (1-13) against α-amylase and α-glucosidase enzymes. The described derivatives demonstrated good inhibitory potential with IC50 values, ranging between 15.04 ± 0.05 to 76.70 ± 0.06 µM ± SEM for α-amylase and 16.99 ± 0.19 to 77.97 ± 0.19 µM ± SEM for α-glucosidase, respectively. In particular, compounds (8-10 and 12) displayed significant inhibitory activities against both the screened enzymes, with their inhibitory potential comparable to the standard acarbose (12.98 ± 0.03 and 12.79 ± 0.17 µM ± SEM, respectively). Additionally, the influence of different substituents on enzyme inhibition activities was assessed to study the structure activity relationships. Molecular docking simulations were performed to rationalize the binding of derivatives/compounds with enzymes. All the synthesized derivatives (1-13) were characterized with the aid of spectroscopic instruments such as 1H-NMR, 13C-NMR, HR-MS, elemental analysis and FTIR.Communicated by Ramaswamy H. Sarma.

Untargeted metabolomics for Achilles heel of engineered nanomaterials' risk assessment.

Owing to the superlative properties, engineered nanomaterials (ENM) are being used in food, cosmetics, medicine, and electronics. Therefore, exogenous ENM can be housed into humans through a multitude of exposure routes, leading to compromise of the biomolecules' functionalities through structural deformations, and even at the metabolic level. Consequently, it is of great importance to understand the perturbations introduced at the metabolic level for the timely risk assessment (RA) of ENM. Current technological advancements in metabolomics empower us to visualize the metabolic dysregulations in biological cells, tissues, and living objects, instigated by the ENM. Given the fact, we propose multitiered untargeted metabolomics for the risk assessment of ENM. We propose largely validated experimental design principles that enable the well-organized and authentic identification of metabolic dysregulation connected with a newly engineered nanomaterial. Our scheme could participate in the enhanced transparency of the RA course of rapidly emerging ENM.

Performance of chitosan polymer as platform during sensors fabrication and sensing applications.

Chitosan is an important polymer produced from deacetylation of several sea and insects crusts. Due to its environmental fate and biological biocompatibility, it can be used in several biological and environmental applications. Sensing of biological compounds in human bodies and also in serum, blood, and different body fluids has found an important application instead of direct determination of the body fluids using complicated tools. Sensing process of biological compounds during bio-analysis of the biological systems, especially human fluids lack of several parameters including: high sensitivity, repeatability, speed of analysis and biocompatibility of the used analytical methods, especially in-vivo analysis. That was due to the time between sample handling and sample determination can change various components and concentrations of the bio-compounds. The need for in-situ analysis was directed the researchers for biosensors to overcome the upgrading problems of bio-analysis. Biosensors were the future of this issue. Chitosan can reserve as great platform for fabrication of different sensors to determine the elements, compounds and body bioactive compounds. The presence of different terminal amino and hydroxyl groups within chitosan framework facilitates the immobilization of different biomarkers to be used as sensing elements for the determined compounds. The use of chitosan as sensors platform was enhanced by using chitosan in its nanoforms.

Effectuality of chitosan biopolymer and its derivatives during antioxidant applications.

Chitosan is an important biopolymer produced from the deacetylation of several seas and insect crusts. Due to its environmental fate and biological biocompatibility, it can be used in several biological and environmental applications. In this review, the potential application of chitosan biopolymer was reviewed due to it is considered an environmental, sustainable, and biologically safe plate form for producing several antioxidants. The different antioxidants fabricated from chitosan biopolymer- an active substrate- and the functional role of the diverse groups, either in chitosan backbone or in the coupled species with chitosan, were reviewed. Different antioxidant types were described, reviewed, and compared with the most famous and traditional antioxidants, such as ascorbic acid, citric acid, and gallic acid. Additionally, the different methods and techniques used in determining the antioxidative tendencies of the antioxidants were extensively described and reviewed.

Novel chitosan/guar gum/PVA hydrogel: Preparation, characterization and antimicrobial activity evaluation.

A series of chitosan/poly(vinyl alcohol)/guar gum (CS/PVA/GG) blends were prepared. The synthesis was carried out using different combinations of CS and GG, while keeping PVA constant by casting solution method. The effect of formaldehyde as a crosslinking agent was also evaluated. The blends were characterized by scanning electron microscopy (SEM), Fourier Transform Infra-red (FTIR) and X-ray powder diffraction (XRD). Additionally, the swelling ratio along with antimicrobial activity was also studied. SEM exhibited the phenomenon that surface morphology was mostly affected by blend ratios and cross-linker. The XRD shows the crystalline structure of blends. The FTIR confirmed the strong intermolecular bonding between polymers. Swelling exhibits that cross-linking affects the hydrophilicity of blends and swelling was excellent for S4 blend. The prepared blends showed promising antimicrobial activity against P. multocida, S. aureus, E. coli, and B. subtilis bacterial agents. The data concludes that GG, CS and PVA ternary blends could possibly be used for the biomedical applications.

An efficient synthesis and reactions of novel indolylpyridazinone derivatives with expected biological activity.

Reaction of 4-anthracen-9-yl-4-oxo-but-2-enoic acid (1) with indole gave the corresponding butanoic acid 2. Cyclocondensation of 2 with hydrazine hydrate, phenyl hydrazine, semicarbazide and thiosemicarbazide gave the pyridazinone derivatives 3a-d. Reaction of 3a with POCl(3) for 30 min gave the chloropyridazine derivative 4a, which was used to prepare the corresponding carbohydrate hydrazone derivatives 5a-d. Reaction of chloropyridazine 4a with some aliphatic or aromatic amines and anthranilic acid gave 6a-f and 7, respectively. When the reaction of the pyridazinone derivative 3a with POCl(3) was carried out for 3 hr an unexpected product 4b was obtained. The structure of 4b was confirmed by its reaction with hydrazine hydrate to give hydrazopyridazine derivative 9, which reacted in turn with acetyl acetone to afford 10. Reaction of 4b with methylamine gave 11, which reacted with methyl iodide to give the trimethylammonium iodide derivative 12. The pyridazinone 3a also reacted with benzene- or 4-toluenesulphonyl chloride to give 13a-b and with aliphatic or aromatic aldehydes to give 14a-g. All proposed structures were supported by IR, (1)H-NMR, (13)C-NMR, and MS spectroscopic data. Some of the new products showed antibacterial activity.