The colony assay in-vitro as a procedure to reduce animal testing in the development of new anticancer drugs

1986 ◽  
Vol 111 (S1) ◽  
pp. S51-S51
Author(s):  
H. H. Fiebig ◽  
J. R. Schmid
Keyword(s):  
Anticancer Drugs ◽  
Animal Testing ◽  
Colony Assay ◽  
New Anticancer Drugs

scholarly journals A multilayered cancer-on-a-chip model to analyze the effectiveness of new-generation photosensitizers

The Analyst ◽  
2020 ◽  
Vol 145 (21) ◽  
pp. 6937-6947
Author(s):  
Magdalena Flont ◽  
Elżbieta Jastrzębska ◽  
Zbigniew Brzózka
Keyword(s):  
Anticancer Drugs ◽  
Three Dimensional ◽  
Cancer Tissue ◽  
Cellular Models ◽  
New Generation ◽  
New Anticancer Drugs

Three-dimensional (3D) cellular models of cancer tissue are necessary tools to analyze new anticancer drugs under in vitro conditions.

scholarly journals In the Search for New Anticancer Drugs, IV+ Antitumor Activity of Seleno-TEPA

1983 ◽  
Vol 38 (9) ◽  
pp. 1138-1141 ◽  
Author(s):  
Maria Konieczny ◽  
Peter L. Gutierrez ◽  
George Sosnovsky
Keyword(s):  
Antitumor Activity ◽  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Human Cell ◽  
Human Cell Lines ◽  
Colony Assay ◽  
Selenium Analog ◽  
New Anticancer Drugs ◽  
Cell Colony

Abstract In order to test the effect of selenium on the anticancer activity of alkylating drugs, Seleno-TEPA (4), the selenium analog of the clinically used Thio-TEPA (1) was tested in vivo against the lymphocytic P 388 and lymphoid L1210 murine leukemias. Compound 4 is more active against P 388 leukemia than against L1210, and appears to be active over a narrower concentration range than Thio-TEPA (1). Compound 4 is less active against P 388 leukemia than 1, as evidenced by the T/C values of 164 for 4 and 239 for 1 at a dose of 4.2 mg/kg. The activity of 4 was also evaluated on the HL60 and K 562 human cell lines. Under the conditions of the cell colony assay technique, Seleno-TEPA (4) is less effective than Thio-TEPA (1).

scholarly journals Bioactive Olivacine Derivatives—Potential Application in Cancer Therapy

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 564
Author(s):  
Beata Tylińska ◽  
Benita Wiatrak
Keyword(s):  
Clinical Trials ◽  
Biological Activity ◽  
Growth Factors ◽  
Anticancer Drugs ◽  
Inhibition Of Growth ◽  
Structure Activity ◽  
Sar Analysis ◽  
New Anticancer Drugs

 Olivacine and its derivatives are characterized by multidirectional biological activity. Noteworthy is their antiproliferative effect related to various mechanisms, such as inhibition of growth factors, enzymes, kinases and others. The activity of these compounds was tested on cell lines of various tumors. In most publications, the most active olivacine derivatives exceeded the effects of doxorubicin (a commonly used anticancer drug), so in the future, they may become the main new anticancer drugs. In this publication, we present the groups of the most active olivacine derivatives obtained. In this work, the in vitro and in vivo activity of olivacine and its most active derivatives are presented. We describe olivacine derivatives that have been in clinical trials. We conducted a structure–activity relationship (SAR) analysis that may be used to obtain new olivacine derivatives with better properties than the available anticancer drugs. 

scholarly journals Unravelling the Allosteric Targeting of PHGDH at the ACT-Binding Domain with a Photoactivatable Diazirine Probe and Mass Spectrometry Experiments

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 477
Author(s):  
Quentin Spillier ◽  
Séverine Ravez ◽  
Simon Dochain ◽  
Didier Vertommen ◽  
Léopold Thabault ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Anticancer Drugs ◽  
Mechanism Of Action ◽  
Rational Design ◽  
Biosynthetic Pathway ◽  
Allosteric Site ◽  
Site Of Action ◽  
Phosphoglycerate Dehydrogenase ◽  
New Anticancer Drugs

The serine biosynthetic pathway is a key element contributing to tumor proliferation. In recent years, targeting of phosphoglycerate dehydrogenase (PHGDH), the first enzyme of this pathway, intensified and revealed to be a promising strategy to develop new anticancer drugs. Among attractive PHGDH inhibitors are the α-ketothioamides. In previous work, we have demonstrated their efficacy in the inhibition of PHGDH in vitro and in cellulo. However, the precise site of action of this series, which would help the rational design of new inhibitors, remained undefined. In the present study, the detailed mechanism-of-action of a representative α-ketothioamide inhibitor is reported using several complementary experimental techniques. Strikingly, our work led to the identification of an allosteric site on PHGDH that can be targeted for drug development. Using mass spectrometry experiments and an original α-ketothioamide diazirine-based photoaffinity probe, we identified the 523Q-533F sequence on the ACT regulatory domain of PHGDH as the binding site of α-ketothioamides. Mutagenesis experiments further documented the specificity of our compound at this allosteric site. Our results thus pave the way for the development of new anticancer drugs using a completely novel mechanism-of-action.

In vitro toxicity evaluation in the development of new anticancer drugs—genistein glycosides

2005 ◽  
Vol 229 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Joanna Popiołkiewicz ◽  
Krzysztof Polkowski ◽  
Janusz S. Skierski ◽  
Aleksander P. Mazurek
Keyword(s):  
Anticancer Drugs ◽  
In Vitro Toxicity ◽  
Toxicity Evaluation ◽  
New Anticancer Drugs

Cytotoxic Effect of the Combination of Gemcitabine and Atorvastatin Loaded in Microemulsion on the HCT116 Colon Cancer Cells

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Therapeutic Potential ◽  
Morphological Changes ◽  
In Vitro Study ◽  
Colon Cancer Cells ◽  
Apoptosis Detection ◽  
Hct116 Cells

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

Recent Design and Structure-Activity Relationship Studies on Modifications of DHFR Inhibitors as Anticancer Agents

2019 ◽  
Vol 26 ◽  
Author(s):  
Agnieszka Wróbel ◽  
Danuta Drozdowska
Keyword(s):  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Physicochemical Characterization ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Biological Research ◽  
Structure Activity ◽  
Dhfr Inhibitors

Background: Dihydrofolate reductase (DHFR) has been known for decades as a molecular target for antibacterial, antifungal and anti-malarial treatments. This enzyme is becoming increasingly important in the design of new anticancer drugs, which is confirmed by numerous studies including modelling, synthesis and in vitro biological research. This review aims to present and discuss some remarkable recent advances on the research of new DHFR inhibitors with potential anticancer activity. Methods: The scientific literature of the last decade on the different types of DHFR inhibitors has been searched. The studies on design, synthesis and investigation structure-activity relationship were summarized and divided into several subsections depending on the leading molecule and its structural modification. Various methods of synthesis, potential anticancer activity and possible practical applications as DHFR inhibitors of new chemical compounds were described and discussed. <p> Results: This review presents the current state of knowledge on the modification of known DHFR inhibitors and the structures and searching for over eighty new molecules, designed as potential anticancer drugs. In addition, DHFR inhibitors acting on thymidylate synthase (TS), carbon anhydrase (CA) and even DNA-binding are presented in this paper. <p> Conclusion: Thorough physicochemical characterization and biological investigations it is possible to understand structure-activity relationship of DHFR inhibitors. This will enable even better design and synthesis of active compounds, which would have the expected mechanism of action and the desired activity.

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