Inhibiting Cyclin-Dependent Kinase 6 by Taurine: Implications in Anticancer Therapeutics.

Cyclin-dependent kinase 6 (CDK6) is linked with a cyclin partner and plays a crucial role in the early stages of cancer development. It is currently a potential drug target for developing therapeutic molecules targeting cancer therapy. Here, we have identified taurine as an inhibitor of CDK6 using combined in silico and experimental studies. We performed various experiments to find the binding affinity of taurine with CDK6. Molecular docking analysis revealed critical residues of CDK6 that are involved in taurine binding. Fluorescence measurement studies showed that taurine binds to CDK6 with a significant binding affinity, with a binding constant of K = 0.7 × 107 M-1 for the CDK6-taurine complex. Enzyme inhibition assay suggested taurine as a good inhibitor of CDK6 possessing an IC50 value of 4.44 µM. Isothermal titration calorimetry analysis further confirmed a spontaneous binding of taurine with CDK6 and delineated the thermodynamic parameters for the CDK6-taurine system. Altogether, this study established taurine as a CDK6 inhibitor, providing a base for using taurine and its derivatives in CDK6-associated cancer and other diseases.

Development of Methanol Sensor Based on Sol-Gel Drop-Coating Co3O4·CdO·ZnO Nanoparticles Modified Gold-Coated µ-Chip by Electro-Oxidation Process.

Herein, novel Co3O4·CdO·ZnO-based tri-metallic oxide nanoparticles (CCZ) were synthesized by a simple solution method in basic phase. We have used Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Field Emission Scanning Electron Microscope (FESEM), Dynamic Light Scattering (DLS), Tunneling Electron Microscopy (TEM), and Energy-Dispersive Spectroscopy (EDS) techniques to characterize the CCZ nanoparticles. XRD, TEM, DLS, and FESEM investigations have confirmed the tri-metallic nanoparticles' structure, while XPS and EDS analyses have shown the elemental compositions of the CCZ nanoparticles. Later, a Au/µ-Chip was modified with the CCZ nanoparticles using a conducting binder, PEDOT: PSS (poly(3,4-ethylenedioxythiophene) polystyrene sulfonate) in a sol-gel system, and dried completely in air. Then, the CCZ/Au/µ-Chip sensor was used to detect methanol (MeOH) in phosphate buffer solution (PBS). Outstanding sensing performance was achieved for the CCZ/Au/µ-Chip sensor, such as excellent sensitivity (1.3842 µAµM-1cm-2), a wide linear dynamic range of 1.0 nM-2.0 mM (R2 = 0.9992), an ultra-low detection limit (32.8 ± 0.1 pM at S/N = 3), a fast response time (~11 s), and excellent reproducibility and repeatability. This CCZ/Au/µ-Chip sensor was further applied with appropriate quantification results in real environmental sample analyses.

Sensitive Detection of Thiourea Hazardous Toxin with Sandwich-Type Nafion/CuO/ZnO Nanospikes/Glassy Carbon Composite Electrodes.

In this research study, we developed a voltammetric electrochemical sensor probe with a copolymer Nafion (Sulfonated Tetrafluoroethylene-based Fluoro-polymer) decorated with hydrothermally prepared sandwich-type CuO/ZnO nanospikes (NSs) onto a glassy carbon electrode (GCE) for reliable thiourea (TU) detection. The detailed characterizations in terms of structural morphology, binding energy, elemental compositions, grain size and crystallinity for synthesized NSs were performed by field emission scanning electron microscopy (FESEM), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD) analysis, respectively. The differential pulse voltammetric (DPV) analysis for TU showed good linearity at current-versus-TU concentration on the calibration plot in the 0.15~1.20 mM range, which is defined as a dynamic detection range (LDR) of TU in a phosphate buffer solution. Considering the slope of LDR over the GCE-coated NSs surface area (0.0316 cm2), the TU sensor sensitivity (0.4122 µA µM-1 cm-2) was obtained. Besides this, the low limit (LOD) for TU detection was calculated and found to be 23.03 ± 1.15 µM. The fabricated Nafion/CuO/ZnO NSs/GCE sensor probe was created as a reliable sensor based on reproducibility, interference effect, stability and response time. Real bio-samples were investigated and the results confirm the anticipated reliability of the TU sensor probe. Thus, this is a noble way to develop enzyme-free electrochemical sensors that could be an alternative approach for the detection of chemicals in the field of enzyme-free biosensor development technology.

Synthesis and Biological Evaluation of 1,2,3-Triazole Tethered Thymol-1,3,4-Oxadiazole Derivatives as Anticancer and Antimicrobial Agents.

A library of 1,2,3-triazole-incorporated thymol-1,3,4-oxadiazole derivatives (6-18) hasbeen synthesized and tested for anticancer and antimicrobial activities. Compounds 7, 8, 9, 10, and 11 exhibited significant antiproliferative activity. Among these active derivatives, compound 2-(4-((5-((2-isopropyl-5-methylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol (9) was the best compound against all three tested cell lines, MCF-7 (IC50 1.1 µM), HCT-116 (IC50 2.6 µM), and HepG2 (IC50 1.4 µM). Compound 9 was found to be better than the standard drugs, doxorubicin and 5-fluorouracil. These compounds showed anticancer activity through thymidylate synthase inhibition as they displayed significant TS inhibitory activity with IC50 in the range 1.95-4.24 µM, whereas the standard drug, Pemetrexed, showed IC50 7.26 µM. The antimicrobial results showed that some of the compounds (6, 7, 9, 16, and 17) exhibited good inhibition on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The molecular docking and simulation studies supported the anticancer and antimicrobial data. It can be concluded that the synthesized 1,2,3-triazole tethered thymol-1,3,4-oxadiazole conjugates have both antiproliferative and antimicrobial potential.

Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies.

A library of novel naproxen based 1,3,4-oxadiazole derivatives (8-16 and 19-26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hybrids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol(15) was the most potent compound against MCF-7 and HepG2cancer cells with IC50 of 2.13 and 1.63 µg/mL, respectively, and was equipotent to doxorubicin (IC50 1.62 µg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC50 0.41 µM compared to standard drug Erlotinib (IC50 0.30 µM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy.