Design and Synthesis of New bis-oxindole and Spiro(triazole-oxindole) as CDK4 Inhibitors with Potent Anti-breast Cancer Activity.

BACKGROUND: Since CDKs have been demonstrated to be overexpressed in a wide spectrum of human malignancies, their inhibition has been cited as an effective technique for anticancer drug development. METHODS: In this context, new bis-oxindole/spiro-triazole-oxindole anti-breast cancer drugs with potential CDK4 inhibitory effects were produced in this work. The novel series of bis-oxindole/spirotriazole- oxindole were synthesized from the reaction of bis-oxindole with the aniline derivatives then followed by 1,3-dipolar cycloaddition of hydrazonoyl chloride. RESULTS: The structure of these bis-oxindole/spiro-triazole-oxindole series was proven based on their spectral analyses. Most bis-oxindole and bis-spiro-triazole-oxindole compounds effectively inhibited the growth of MCF-7 (IC50 = 2.81-17.61 µM) and MDA-MB-231 (IC50 = 3.23-7.98 µM) breast cancer cell lines with low inhibitory activity against normal WI-38 cells. While the reference doxorubicin showed IC50 values of 7.43 µM against MCF-7 and 5.71 µM against the MDA-MB-231 cell line. Additionally, compounds 3b, 3c, 6b, and 6d revealed significant anti-CDK4 activity (IC50 = 0.157- 0.618 µM) compared to palbociclib (IC50 = 0.071 µM). Subsequent mechanistic investigations demonstrated that 3c was able to trigger tumor cell death through the induction of apoptosis. Moreover, it stimulated cancer cell cycle arrest in the G1 phase. Furthermore, western blotting disclosed that the 3c-induced cell cycle arrest may be mediated through p21 upregulation. CONCLUSION: According to all of the findings, bis-oxindole 3c shows promise as a cancer treatment targeting CDK4.

Immobilization of biomolecular anthocyanin natural sensor into plasma-cured polyethylene terephthalate fibers from recycled plastic waste for determination of ammonia.

Polyester textiles have been applied in numerous industrial applications. Polyester fibers are characterized with being excellent insulators to electricity, having excellent flexural and impact strength, ease of manufacture, low-cost, as well as having resistance to moisture and chemicals. However, polyester fibers cannot be stained due to the absence of active dyeing sites on the surface of the fibrous structure. Thus, polyester cannot be dyed after it has been extruded. Herein, we report the development of novel-colored polyester fabrics using plasma-assisted dyeing and anthocyanin natural probe for determination of ammonia that may cause severe harmful effects to human organs and even death. Anthocyanin was extracted from red cabbage and characterized. The water-soluble anthocyanin was fastened to polyester fibers by mordant (potash alum) to generate anthocyanin-mordant coordinative complex nanoparticles. Polyester can be treated with thin layer of anthocyanin probe after activation with plasma. The results showed excellent colorfastness, ultraviolet blocking, and antibacterial performance of the anthocyanin-dyed polyester (APET) fibers. The APET fibers showed great potential for developing a portable colorimetric device for an on-site detection of ammonia. APET displayed a detection limit of aqueous ammonia in the range of 25-200 ppb, displaying a change in color from purple (542 nm) to white (387 nm).

Novel thiazole derivatives incorporating phenyl sulphonyl moiety as potent BRAFV600E kinase inhibitors targeting melanoma.

Novel thiazole derivatives possessing phenyl sulfonyl moiety were designed and synthesized as B-RAFV600E kinase inhibitors based on the clinically-approved anticancer drug, dabrafenib. All target compounds showed significant inhibition of B-RAFV600E kinase enzyme at nanomolar levels. Compounds 7b and 13a revealed excellent B-RAFV600E inhibitory activity, superior to that of dabrafenib with IC50 values of 36.3 ± 1.9, 23.1 ± 1.2, and 47.2 ± 2.5 nM, respectively. Moreover, the title compounds were much more selective toward B-RAFV600E kinase than B-RAF wild type. In addition, the most potent compounds were further evaluated for their anticancer activity against B-RAFV600E-mutated and wild type melanoma cells. A positive correlation between the cytotoxic activity and selectivity for B-RAF V600E over B-RAF wild type was clearly observed for compounds 7b, 11c, 13a, and 17. All the screened compounds potently inhibited the growth of WM266.4 melanoma cells with IC50 values in the range from 1.24 to 17.1 µM relative to dabrafenib (IC50 = 16.5 ± 0.91 µM). Compounds 7b, 11a and 11c, 13a, and 17 were much more potent than dabrafenib against B-RAFV600E-mutated WM266.4 melanoma cells. Furthermore, compound 7b suppressed the phosphorylation of downstream ERK1/2 from WM266.4 cells. Also, the docking study revealed the proper orientation and well-fitting of the title compounds into the ATP binding site of B-RAFV600E kinase.

Solution blowing spinning of polylactate/polyvinyl alcohol/ZnO nanocomposite toward green and sustainable preparation of wound dressing nanofibrous films.

The outstanding biodegradability, biocompatibility, affordability, and renewability of polylactic acid have made it a prominent biomaterial. Herein, an innovative, easy, and eco-friendly technique is used to prepare sodium polylactate (SP)-based nanofibers. Solution blowing spinning (SBS) was used to create fibrous mats of SP and polyvinyl alcohol (PVA). SBS's SP nanfibers were crosslinked using an aqueous solution of calcium chloride to produce moisture-resistant calcium polylactate nanofibrous spun mats. Both of UV-visible absorption spectra and transmission electron microscopy were utilized to study the produced zinc oxide (ZnO) nanoparticles (NPs) to indicate a diameter of around 15-23 nm with a high intensity absorption intensity at 370 nm. New polylactate copolymer was synthesized and characterized by infrared and NMR spectroscopic techniques. In order to prepare SP/PVA/ZnO nanocomposite nanofibers, various ZnO ratios were used. The morphologies of the composite nanofibers were investigated by infrared spectroscopy (FTIR), energy-dispersive X-ray analyzer, and scanning electron microscopy. The cytotoxicity tests of the prepared mat were studied by conducting experiments with L-929 cells at various time intervals. The prepared composite SP/PVA/ZnO nanofibers were subjected to cytotoxicity tests to determine their cytocompatibility. Results showed that those with ZnO concentrations between 0.5% and 2% were found to be less harmful than those with higher concentrations. A variety of bacterial species, including Bacillus pumilus and Staphylococcus aureus, as well as Klebseilla pneumoniae and Escherichia coli, were used to test the antibacterial properties of SP/PVA/ZnO spun mats. The ZnO NPs integrated in the SP/PVA fibrous mats were responsible for their antibacterial properties. After finding the appropriate concentration of ZnO that is least harmful while yet giving a satisfactory antibacterial activity, this biomaterial might be perfect for wound dressing applications. HIGHLIGHTS: New eco-friendly biodegradable sodium polylactate (SP) copolymer was synthesized. Zinc oxide nanoparticles (ZnO NPs) with a diameter of 15-23 nm were prepared. High antibacterial SP/PVA/ZnO fibers were prepared by solution blowing spinning. SP/PVA/ZnO nanofibers (180-220 nm) with various ratios of ZnO were presented. Cytotoxicity results showed that the cell viability decreases with increasing ZnO.

Cellulose Acetate-Cellulose Nanowhisker Nanocomposite Immobilized with a DCDHF-Hydrazone Chromophore toward a Smart Test Strip for Colorimetric Detection of Diethyl Chlorophosphate as a Nerve Agent Mimic.

Exposure to nerve agents, which are usually colorless and odorless gases, may cause organ failure, paralysis, or even quick death. Diethyl chlorophosphate (DCP) has been recognized as one of the most well-known chemical warfare nerve agent mimics. In the current study, we introduce a simple strategy for the development of a portable and reversible nanocomposite-based microporous strip for naked-eye detection of DCP within a few seconds. A dicyanomethylenedihydrofuran hydrazone (DCDHF-H) chromophore was synthesized by an easy azo-coupling reaction and encapsulated in situ during the preparation of cellulose acetate/cellulose nanowhisker/hydrazone (CA-CNW-H) nanocomposites. These CA-CNW-H nanocomposites displayed a bathochromic shift in the absorption intensity of about 142 nm from 438 to 580 nm with the increase of the DCP concentration. The present CA-CNW-H sensor strip displayed a detection limit for DCP ranging from 25 to 200 ppm. The color change of CA-CNW-H from yellow to purple due to exposure to DCP was detected by CIE Lab analysis. The morphology, fibrous crystallinity, thermal stability, and mechanical properties of the prepared CA-CNW-H sensor strips were investigated.

Luminescence feature of new 3,6-di(thiazolidin-5-one-2-yl)-carbazole derivative: synthesis, photophysical properties, density functional theory studies, and crystal shape effect.

A new carbazole chromophore conjugated with substituted thiazolidine-4-one (CzPT) was synthesized by applying the Knoevenagel reaction between 3,6-diformyl-N-hexylcarbazole and ethyl 2-aceto-2-(5-oxo-3-phenylthiazolidin-2-ylidene)acetate. The chemical structure of the new derivative (CzPT) was elucidated by spectral studies. The CzPT absorption spectra in different solvents exhibited a red shift for λmax by increasing solvent polarity. Bands at 430-474 nm appeared and were attributed to intramolecular charge transfer with high π-π* characteristics. CzPT fluorescence spectra exhibited a red shift after increasing the solvent polarity. To understand the Stokes' shift ( ∆ ν ¯ ) behaviour of the CzPT derivative referring to the polarity of solvents, Lippert-Mataga and linear solvation-energy relationship (LSER) models were employed in which the LSER exhibited respectable results compared with Lippert-Mataga (r2 = 0.9707). Moreover, time-dependent density functional theory absorption spectra in hexane and dimethylformamide showed that λmax had a major contribution in the highest occupied molecular orbital to lowest unoccupied molecular orbital transition in both solvents. In addition, the reduced uniformity of crystal features may lead to dislocation or anomalous arrangement of crystals with irregular spacing, which automatically enhances the optical properties of such crystals.