Changes in the Sensitivity of MCF-7 and MCF-7/DX Breast Cancer Cells to Cytostatic in the Presence of Metformin.

Multidrug resistance is a serious problem in modern medicine and the reason for the failure of various therapies. A particularly important problem is the occurrence of multidrug resistance in cancer therapies which affects many cancer patients. Observations on the effect of metformin-a well-known hypoglycemic drug used in the treatment of type 2 diabetes-on cancer cells indicate the possibility of an interaction of this substance with drugs already used and, as a result, an increase in the sensitivity of cancer cells to cytostatics.

Synthesis, Docking, and Machine Learning Studies of Some Novel Quinolinesulfonamides-Triazole Hybrids with Anticancer Activity.

In the presented work, a series of 22 hybrids of 8-quinolinesulfonamide and 1,4-disubstituted triazole with antiproliferative activity were designed and synthesised. The title compounds were designed using molecular modelling techniques. For this purpose, machine-learning, molecular docking, and molecular dynamics methods were used.

Evaluation of Physician Knowledge of Safety and Safe Use Information for Intravitreal Aflibercept Injection in Europe: A Second Survey of Physicians Following Dissemination of Updated Risk-Minimization Materials.

Background: Materials have been distributed in the European Union to inform physicians on the safe use of intravitreal aflibercept (IVT-AFL) as part of the risk-minimization plan for IVT-AFL.

Objective: We aimed to measure physician knowledge and understanding of key safety information for IVT-AFL.

Methods: The current study was a follow-up cross-sectional survey ('wave 2') to an earlier survey ('wave 1') examining the effectiveness of the IVT-AFL educational materials by assessing physician knowledge of the key safety information.

EURADOS project on the impact of the proposed ICRU operational dose quantities.

Following the publication of the joint The International Commissions on Radiation Units and Measurements (ICRU) and on Radiological Protection (ICRP) report on new operational quantities for radiation protection, the European Dosimetry Group (EURADOS) have carried out an initial evaluation. The EURADOS report analyses the impact that the new quantities will have on: radiation protection practice; calibration and reference fields; European and national regulation; international standards and, especially, dosemeter and instrument design. The task group included experienced scientists drawn from across the various EURADOS working groups.

Towards Anticancer and Antibacterial Agents: Design and Synthesis of 1,2,3-Triazol-quinobenzothiazine Derivatives.

In this paper, we describe a new method for synthesizing hybrid combinations of 1,2,3-triazoles with a tetracyclic quinobenzothiazinium system. The developed approach allowed for the production of a series of new azaphenothiazine derivatives with the 1,2,3-triazole system in different positions of the benzene ring. In practice, the methodology consists of the reaction of triazole aniline derivatives with thioquinanthrenediinium -chloride.

Design, Synthesis and Biological Evaluation of Quinoline-8-Sulfonamides as Inhibitors of the Tumor Cell-Specific M2 Isoform of Pyruvate Kinase: Preliminary Study.

Cancer cells need to carefully regulate their metabolism to keep them growing and dividing under the influence of different nutrients and oxygen levels. Muscle isoform 2 of pyruvate kinase (PKM2) is a key glycolytic enzyme involved in the generation of ATP and is critical for cancer metabolism. PKM2 is expressed in many human tumors and is regulated by complex mechanisms that promote tumor growth and proliferation.

Design, Synthesis and Antimicrobial Properties of New Tetracyclic Quinobenzothiazine Derivatives.

A new method for modifying the structure of tetracyclic quinobenzothiazinium derivatives has been developed, allowing introduction of various substituents at different positions of the benzene ring. The method consists of reacting appropriate aniline derivatives with 5,12-(dimethyl)thioquinantrenediinium bis-chloride. A series of new quinobenzothiazine derivatives was obtained with propyl, allyl, propargyl and benzyl substituents in 9, 10 and 11 positions, respectively.

Hybrids of 1,4-Quinone with Quinoline Derivatives: Synthesis, Biological Activity, and Molecular Docking with DT-Diaphorase (NQO1).

Hybrids 1,4-quinone with quinoline were obtained by connecting two active structures through an oxygen atom. This strategy allows to obtain new compounds with a high biological activity and suitable bioavailability. Newly synthesized compounds were characterized by various spectroscopic methods.

[Anti-cancer properties of dichloroacetate].

One of the hallmarks of cancer cells is aerobic glycolysis (the Warburg effect). The effect of dichloroacetate (DCA) is to switch glucose metabolism (cellular respiration) to a more efficient process involving oxygen, reduce the production of lactic acid, activate the respiratory chain, change the potential of the mitochondrial membrane, and release pro-apoptotic mediators (cytochrome c and AIF) into the cytosol. As a result, the control over the mutated cells is improved, their sensitivity to various drugs or radiotherapy and their sensitivity to apoptosis increase.

[A multidirectional effect of metformin].

Diabetes as chronic civilization disease, very often occurs together with health disorders. One of the basic pharmaceuticals commonly used in her therapy is metformin. Many other positive effects, not related to diabetes, have been observed in tatients treated with metformin for a long time.

Towards Property Profiling: SYNTHESIS and SAR Probing of New Tetracyclic Diazaphenothiazine Analogues.

A series of new tertiary phenothiazine derivatives containing a quinoline and a pyridine fragment was synthesized by the reaction of 1-methyl-3-benzoylthio-4-butylthioquinolinium chloride with 3-aminopyridine derivatives bearing various substituents on the pyridine ring. The direction and mechanism of the cyclization reaction of intermediates with the structure of 1-methyl-4-(3-pyridyl)aminoquinolinium-3-thiolate was related to the substituents in the 2- and 4-pyridine position. The structures of the compounds were analyzed using H, C NMR (COSY, HSQC, HMBC) and X-ray analysis, respectively.

Structural and spectral characterisation of 2-amino-2H-[1,2,3]triazolo[4,5-g]quinoline-4,9-dione polymorphs. Cytotoxic activity and molecular docking study with NQO1 enzyme.

Depending on temperature, the 2-amino-2H-[1,2,3]triazolo[4,5-g]quinoline-4,9-dione forms two polymorphic structures, which differ in the spatial arrangement of the amine group. Both polymorphs were investigated using different experimental methods as well as various quantum chemical calculations in order to characterise their molecular structures. We used X-ray diffraction, FT-IR and NMR (solid-state and liquid) methods supplemented by the density functional theory (DFT) calculations, molecular electrostatic potential (MEP) and molecular orbital (HOMO, LUMO) analyses.

Design, Synthesis, and Structural Characterization of Novel Diazaphenothiazines with 1,2,3-Triazole Substituents as Promising Antiproliferative Agents.

A series of novel 1,2,3-triazole-diazphenothiazine hybrids was designed, synthesized, and evaluated for anticancer activity against four selected human tumor cell lines (SNB-19, Caco-2, A549, and MDA-MB231). The majority of the synthesized compounds exhibited significant potent activity against the investigated cell lines. Among them, compounds and showed excellent broad spectrum anticancer activity, with IC values ranging from 0.

Evaluation of angularly condensed diquinothiazines as potential anticancer agents.

We present efficient synthesis of isomeric types of angularly fused diquinothiazines in the reactions of 2,2'-dichloro-3,3'-diquinolinyl disulfide and diquinodithiin with 3-, 5-, 6- and 8-aminoquinolines. The pentacyclic diquinothiazine ring systems were identified as diquino[3,2-b;3',4'-e][1,4]thiazine, diquino[3,2-b;5',6'-e][1,4]thiazine, diquino[3,2-b;6',5'-e][1,4]thiazine and diquino[3,2-b;8',7'-e][1,4]thiazine with advanced two-dimensional H and C NMR techniques (COSY, ROESY, HSQC and HMBC) of N-methyl derivatives. The identification of pentacyclic ring system was confirmed by X-ray diffraction analysis of selected N-alkyl derivatives.

Synthesis, Anticancer Activity, and Apoptosis Induction of Novel 3,6-Diazaphenothiazines.

New 10-substituted derivatives of 3,6-diazaphenothiazine, containing the triple bond linker terminated with tertiary cyclic and acyclic amine groups, were synthesized and screened for their anticancer action. The compounds exhibited varied anticancer activities against human glioblastoma SNB-19, melanoma C-32, and breast cancer MDA-MB231 cell lines, depending on the nature of the substituents. The most active 3,6-diazaphenothiazine, , was the derivative with the ,-diethylamino-2-butynyl substituent against glioblastoma SNB-19, and was ten times more potent than cisplatin.

Novel triazoles of 3-acetylbetulin and betulone as anticancer agents.

The CuAAC reaction of azides and acetylenic triterpenes was used for synthesis of new triazoles of 3-acetylbetulin and betulone. The triazole derivatives were evaluated for their anticancer activity in vitro against amelanotic melanoma C-32, ductal carcinoma T47D and glioblastoma SNB-19 cell lines. 28-[1-(3'-Deoxythymidine-5'-yl)-1-1,2,3-triazol-4-yl]carbonylbetulone exhibited a significant IC value (0.

Synthesis and anticancer activity of multisubstituted purines and xanthines with one or two propynylthio and aminobutynylthio groups.

A synthesis of new 2,6-disubstituted and 2,6,8-trisubstituted 7-methylpurines as well as 8-substituted 3,7-dimethylxanthines containing a triple bond chain have been worked out. Purinethiones and xanthinethiones were converted into propynylthio derivatives, which were then further transformed via a Mannich reaction into aminobutynylthio derivatives (amine = pyrrolidine, piperidine, morpholine, and diethylamine). The products thus obtained represent various types of the purine and xanthine structure: 8-mono-, 2,6- and 6,8-dipropynylthio, 6- and 8-monoaminobutynylthio, 2,6- and 6,8-diaminobutynylthio derivatives.

Novel Triazole Hybrids of Betulin: Synthesis and Biological Activity Profile.

Betulin derivatives containing a 1,2,3-triazole ring possess a wide spectrum of biological activities, including antiviral, anticancer, and antibacterial activity. A series of novel triazoles were prepared by the 1,3-dipolar cycloaddition reaction between the alkyne derivatives of betulin and organic azides. The chemical structures of the obtained compounds were defined by ¹H and C NMR, IR, and high-resolution mass spectrometry (HR-MS) analysis.

Alkoxy and Enediyne Derivatives Containing 1,4-Benzoquinone Subunits-Synthesis and Antitumor Activity.

The compounds produced by a living organism are most commonly as medicinal agents and starting materials for the preparation of new semi-synthetic derivatives. One of the largest groups of natural compounds consists of products containing a 1,4-benzoquinone subunit. This fragment occurs in three enediyne antibiotics, dynemicin A, deoxydynemicin A, and uncilamicin, which exhibit high biological activity.

Synthesis, Anti-Breast Cancer Activity, and Molecular Docking Study of a New Group of Acetylenic Quinolinesulfonamide Derivatives.

In this study, a series of regioisomeric acetylenic sulfamoylquinolines are designed, synthesized, and tested in vitro for their antiproliferative activity against three human breast cacer cell lines (T47D, MCF-7, and MDA-MB-231) and a human normal fibroblast (HFF-1) by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay. The antiproliferative activity of the tested acetylenic quinolinesulfonamides is comparable to that of cisplatin. The bioassay results demonstrate that most of the tested compounds show potent antitumor activities, and that some compounds exhibit better effects than the positive control cisplatin against various cancer cell lines.