scholarly journals Synthesis and Anticancer Activity of Gold(I)-Chloroquine Complexes

2017 ◽  
Vol 57 (3) ◽  
Author(s):  
Maribel Navarro ◽  
William Castro ◽  
Sorenlis González ◽  
María Jesús Abad ◽  
Peter Taylor
Keyword(s):  
Experimental Data ◽  
Anticancer Agents ◽  
Covalent Binding ◽  
Thioredoxin Reductase ◽  
Analytical Techniques ◽  
Tumor Cell Lines ◽  
Probable Structure ◽  
Covalent Interaction ◽  
Ht 29 ◽  
Most Probable Structure

Two new gold(I) -chloroquine complexes, Au(CQ)(Cl) (<strong>1</strong>) and Au(CQ)(tgta) (<strong>2</strong>), were prepared and their most probable structure were established through a combination of different spectroscopic and analytical techniques. Their interaction with two important targets of action, DNA and thioredoxin reductase (TrxR), were nvestigated. These studies showed that complexes <strong>1</strong> and <strong>2</strong> displayed two types of interaction with DNA, covalent binding through the metal center, and additionally a non-covalent interaction that is electrostatic in the case of complex <strong>1</strong>, but intercalative for complex <strong>2</strong>, which is similar to that displayed by free CQ. The experimental data indicated that these gold-CQ complexes also possess the ability to inhibit TrxR. These results led us to test their cytotoxicity against 6 tumor cell lines. The complexes displayed cytotoxic activity against the PC-3, SKBR-3, HT-29, LoVo and B16/BL6 lines. These finding suggest that gold(I)-CQ compounds, particularly [Au(CQ)(PPh<sub>3</sub>)]PF<sub>6</sub>, are promising chemotherapeutic alternatives in the search of anticancer agents.

Synthesis and Biological Evaluation of Novel 4,5,6,7-Tetrahydrobenzo[D]-Thiazol-2- Yl Derivatives Derived from Dimedone with Anti-Tumor, C-Met, Tyrosine Kinase and Pim-1 Inhibitions

2019 ◽  
Vol 19 (12) ◽  
pp. 1438-1453 ◽  
Author(s):  
Rafat M. Mohareb ◽  
Amr S. Abouzied ◽  
Nermeen S. Abbas
Keyword(s):  
Tyrosine Kinase ◽  
Tumor Cell ◽  
Cell Lines ◽  
Single Molecule ◽  
Anticancer Agents ◽  
Biological Evaluation ◽  
New Drugs ◽  
Tumor Cell Lines ◽  
Thiazole Derivatives ◽  
Wide Range

Background: Dimedone and thiazole moieties are privileged scaffolds (acting as primary pharmacophores) in many compounds that are useful to treat several diseases, mainly tropical infectious diseases. Thiazole derivatives are a very important class of compounds due to their wide range of pharmaceutical and therapeutic activities. On the other hand, dimedone is used to synthesize many therapeutically active compounds. Therefore, the combination of both moieties through a single molecule to produce heterocyclic compounds will produce excellent anticancer agents. Objective: The present work reports the synthesis of 47 new substances belonging to two classes of compounds: Dimedone and thiazoles, with the purpose of developing new drugs that present high specificity for tumor cells and low toxicity to the organism. To achieve this goal, our strategy was to synthesize a series of 4,5,6,7-tetrahydrobenzo[d]-thiazol-2-yl derivatives using the reaction of the 2-bromodimedone with cyanothioacetamide. Methods: The reaction of 2-bromodimedone with cyanothioacetamide gave the 4,5,6,7-tetrahydrobenzo[d]- thiazol-2-yl derivative 4. The reactivity of compound 4 towards some chemical reagents was observed to produce different heterocyclic derivatives. Results: A cytotoxic screening was performed to evaluate the performance of the new derivatives in six tumor cell lines. Thirteen compounds were shown to be promising toward the tumor cell lines which were further evaluated toward five tyrosine kinases. Conclusion: The results of antitumor screening showed that many of the tested compounds were of high inhibition towards the tested cell lines. Compounds 6c, 8c, 11b, 11d, 13b, 14b, 15c, 15g, 21b, 21c, 20d and 21d were the most potent compounds toward c-Met kinase and PC-3 cell line. The most promising compounds 6c, 8c, 11b, 11d, 13b, 14b, 15c, 15g, 20c, 20d, 21b, 21c and 21d were further investigated against tyrosine kinase (c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR). Compounds 6c, 11b, 11d, 14b, 15c, and 20d were selected to examine their Pim-1 kinase inhibition activity the results revealed that compounds 11b, 11d and 15c had high activities.

New Spirocyclic Hydroxamic Acids as Effective Antiproliferative Agents

2020 ◽  
Vol 20 ◽  
Author(s):  
Margarita E. Neganova ◽  
Sergey G. Klochkov ◽  
Yulia R. Aleksandrova ◽  
Vladimir N. Osipov ◽  
Dmitry V. Avdeev ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Histone Deacetylase ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Antioxidant Activities ◽  
Hydroxamic Acids ◽  
Cytotoxic Activities ◽  
Tumor Cell Lines ◽  
Hek 293 ◽  
Underlying Mechanisms

Aims: The main goal of this work where is to synthesize new original spirocyclic hydroxamic acids, investigate their cytotoxicity against to the panel of tumor cell lines and possible mechanism of action of these active compounds. Background: Hydroxamic acids are one of the promising classes of chemical compounds with proven has anticancer potential properties. This is manifested in the presence of metal chelating and antioxidant activities, the ability to inhibit histone deacetylase enzymes and a chemosensitizing effect against well known cytostatics. Objective: Original spirocyclic hydroxamic acids were synthesized and spectrums of their antiproliferative activities were investigated. Methods: The cytotoxic activities on different tumor lines (SH-SY5Y, HeLa and healthy cells HEK-293) were investigated and determined possible underlying mechanisms of their activity. Result: New original spirocyclic hydroxamic acids were synthesized. These compounds exhibit antiproliferative properties against of the various tumor cultures cells and also exhibits antioxidant activity, a depolarizing effect on the mitochondrial membrane, inhibit the activity of the histone deacetylase enzyme, and also decrease of basal glycolysis and glycolytic capacity reserve of HeLa and SH-SY5Y tumor cell lines. Conclusion: The most promising are compounds 5j-l containing two chlorine atoms as substituents in the quinazoline part of the molecule and hydroxamate function. Therefore, these compounds can be considered as hit compounds for the development on their basis multi-target anticancer agents.

Dimensions de micelles mixtes de p-alkylbenzènesulfonates par diffusion central des rayons X

1977 ◽  
Vol 10 (1) ◽  
pp. 37-44 ◽  
Author(s):  
C. Cabos ◽  
P. Delord ◽  
J. Rouviere
Keyword(s):  
Small Angle ◽  
Small Angle Scattering ◽  
Micellar Solutions ◽  
Probable Structure ◽  
X Ray ◽  
Absolute Scale ◽  
Angle Scattering ◽  
Scattering Measurements ◽  
Two Component ◽  
Most Probable Structure

The structure of micellar solutions is determined from X-ray small-angle scattering measurements on an absolute scale. The most probable structure is chosen by comparison with spherical cylindrical and lamellar models. This method is applied to two-component micelles and it is possible to follow the variation of micellar dimensions when the concentration of each component is varying.

Recent Advances in the Development of Thioredoxin Reductase Inhibitors as Anticancer Agents

2012 ◽  
Vol 13 (11) ◽  
pp. 1432-1444 ◽  
Author(s):  
Yang Liu ◽  
Yijing Li ◽  
Shenghui Yu ◽  
Guisen Zhao
Keyword(s):  
Anticancer Agents ◽  
Thioredoxin Reductase ◽  
Reductase Inhibitors ◽  
Recent Advances

scholarly journals In Vitro Antitumor Activity of Endophytic Fungi Isolated From the Mexican Cactus Pachycereus Marginatus (DC.) Britton & Ros

2021 ◽  
Author(s):  
Jesica M. Ramírez-Villalobos ◽  
César I. Romo-Sáenz ◽  
Karla S. Morán Santibañez ◽  
Patricia Tamez-Guerra ◽  
Ramiro Quintanilla-Licea ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Endophytic Fungi ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Normal Cells ◽  
Human Tumor Cell Lines ◽  
Ht 29 ◽  
Mcf 7

Abstract Background: Arid zone plants such as cacti are known to harbor diverse groups of endophytic fungi, which represent potential sources of new compounds with anticancer properties. In the present study we isolated, identified, and characterized Pachycereus marginatus (DC.) Britton & Ros endophytic fungi with cytotoxic activity against murine and human tumor cell lines.Methods: Endophytic fungi were isolated from P. marginatus stems. Methanol extracts were then obtained from fungi liquid cultures and their cytotoxic activity at concentrations ranging from 31 µg/ml to 250 µg/ml against murine L5178Y-R lymphoma, human colorectal adenocarcinoma HT-29, and human breast cancer MCF-7 was evaluated by the colorimetric 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide reduction assay, using the normal cells Macacus rhesus monkey epitelial kidney MA-104 and human peripheral blood mononuclear cells (PBMC) as controls. IC50 values were obtained and the selectivity index (SI) was calculated from the IC50 ratio of cancer cells and normal cells. Furthermore, molecular identification of fungi showing cytotoxic activity was determined by the internal transcribed spacer molecular marker.Results: The Cladosporium sp. PME-H008 strain showed significant (P < 0.01) 94.3% and 36.8% cytotoxicity against L5178Y-R and HT-29 cells, respectively. The highest SI was observed by L5178Y-R cells with 2.4 and 2.9 for MA-104 and PBMC respectively. In addition, the Metarhizium anisopliae PME-H007 strain was more effective against MCF-7 with 55.8% cytotoxicity. The lowest IC50 was obtained with the Aspergillus sp. PME-H005 strain at 95.21 µg/ml against the MCF-7 cell line, followed by PME-H008 strain at 101 µg/ml against L5178Y-R cells.Conclusion: P. marginatus endophytic fungi showed in vitro cytotoxic activity against murine and human tumor cell lines, without affecting normal cells.

Using Exponential Cubic Splines to Predict Low Temperature Behavior of Elastomeric Materials

1994 ◽  
Author(s):  
Terry E. Shoup ◽  
George R. Fegan
Keyword(s):  
Experimental Data ◽  
Elastic Modulus ◽  
Low Temperatures ◽  
Analytical Techniques ◽  
High Sensitivity ◽  
Considerable Difficulty ◽  
Spline Curves ◽  
Different Types ◽  
Elastomeric Materials ◽  
Energy Absorbing

Abstract Because of their desirable elastic and energy absorbing properties, elastomeric materials have been widely used as shock mounts and pressure seals. The high sensitivity of the elastic modulus of these materials to changes in temperature has been a source of considerable difficulty to the development of robust design methods based on analytical techniques. This paper presents a simple analytical method for predicting the elastic modulus for a group of five different types of elastomers when used at low temperatures. The method is based on the application of exponential cubic spline curves to smooth experimental data. The method is applied to experimental data from the literature to illustrate its usefulness.

Histone H1 Interacts Preferentially with DNA Fragments Containing a Cisplatin- Induced 1,2-Intrastrand Cross-Link

2007 ◽  
Vol 62 (11-12) ◽  
pp. 905-908 ◽  
Author(s):  
Julia N. Yaneva ◽  
Elena G. Paneva ◽  
Siyka I. Zacharieva ◽  
Jordanka Zlatanova
Keyword(s):  
Experimental Data ◽  
Anticancer Agents ◽  
Histone H1 ◽  
Recent Experimental Data ◽  
Band Shift ◽  
Single Target ◽  
Shift Analysis ◽  
Modified Dna ◽  
Cross Links ◽  
Dna Fragment

Cisplatin [cis-diamminedichloroplatinum(II) or cis- DDP], but not its stereoisomer transplatin, is suggested to be among the most powerful anticancer agents. It is believed that its therapeutic activity results from its interaction with DNA forming intra- and interstrand crosslinks. During our earlier investigations, we have observed a prominent preference of the linker histone H1 for binding to cis-platinated DNA (containing several different cross-links along the DNA fragment) compared with unmodified or transplatin-modified DNA. This report presents our recent experimental data obtained by band-shift analysis on the binding of H1 to a cisplatin-modified synthetic 34 bp DNA fragment containing a single target d(GG/CC) for 1,2 cis-intra-platination. Results obtained with another nuclear protein with similar DNA-binding properties, HMGB1, are also presented. The experimental data throw light on the precise preference of histone H1 for binding to different types of cisplatin-created cross-links in DNA.

scholarly journals Chlorinated cobalt alkyne complexes derived from acetylsalicylic acid as new specific antitumor agents

2018 ◽  
Vol 47 (12) ◽  
pp. 4341-4351 ◽  
Author(s):  
Victoria Obermoser ◽  
Daniel Baecker ◽  
Carina Schuster ◽  
Valentin Braun ◽  
Brigitte Kircher ◽  
...  
Keyword(s):  
Antitumor Agents ◽  
Tumor Cell Lines ◽  
Growth Inhibitory ◽  
Cox 2 ◽  
Alkyne Complexes ◽  
Inhibitory Potential ◽  
Cox 2 Inhibitors ◽  
Ht 29 ◽  
Cox 1 ◽  
Mcf 7

Chlorine-substituted [(prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl complexes are selective COX-2 inhibitors with growth-inhibitory potential against COX-1/2 containing MDA-MB-231 and HT-29 tumor cell lines. The metabolic activity of non-tumorigenic HS-5 cells and COX-1/2-independent MCF-7 cells is not influenced.

Sulforaphane, a Chemopreventive Compound, Inhibits Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Expression in Human HT-29 Colon Cancer Cells

2018 ◽  
Vol 206 (1-2) ◽  
pp. 46-53 ◽  
Author(s):  
Maryam Sadat Tafakh ◽  
Massoud Saidijam ◽  
Tayebeh Ranjbarnejad ◽  
Sara Malih ◽  
Solmaz Mirzamohammadi ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Caspase 3 ◽  
Mrna Level ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Prostaglandin E Synthase ◽  
Cox 2 ◽  
Ht 29 ◽  
Microsomal Prostaglandin E Synthase

Background: A high expression of prostaglandin E2 (PGE2) is found in colorectal cancer. Therefore, blocking of PGE2 generation has been identified as a promising approach for anticancer therapy. Sulforaphane (SFN), an isothiocyanate derived from glucosinolate, is used as the antioxidant and anticancer agents. Methods: HT-29 cells were treated with various concentrations of SFN and compared to untreated cells for the expression of microsomal prostaglandin E synthase-1 (mPGES-1), cyclooxygenase 2 (COX-2), hypoxia-inducible factor-1 (HIF-1), C-X-C chemokine receptor type 4 (CXCR4), vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-2 and MMP-9 at the mRNA level. The PGE2 level was measured by ELISA assay. Apoptosis was evaluated by the proportion of sub-G1 cells. The activity of caspase-3 was determined using an enzymatic assay. HT-29 cell migration was assessed using a scratch test. Results: SFN preconditioning decreased the expression of COX-2, mPGES-1, HIF-1, VEGF, CXCR4, MMP-2, and MMP-9. An apoptotic effect of SFN was preceded by the activation of caspase-3 as well as accumulation of cells in the sub-G1 phase of the cell cycle. SFN decreased PGE2 generation and inhibited the in vitro motility/wound-healing activity of HT-29 cells. Conclusions: SFN anticancer effects are associated with antiproliferative, antiangiogenic, and antimetastatic activities arising from the downregulation of the COX-2/ mPGES-1 axis.

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