We have located links that may give you full text access.
Synthesis and anti-breast cancer activity of novel indibulin related diarylpyrrole derivatives.
BACKGROUND: During recent years, a number of anti-tubulin agents were introduced for treatment of diverse types of cancer. Despite their potential in the treatment of cancer, drug resistance and adverse toxicity, such as peripheral neuropathy, are some of the negative effects of anti-tubulin agents. Among anti-tubulin agents, indibulin was found to cause minimal peripheral neuropathy. Thus far, however, indibulin has not entered clinical usage, caused in part by its poor aqueous solubility and other developmental problems in preclinical evaluation.
OBJECTIVES: With respect to need for finding potent and safe anticancer agents, in our current research work, we synthesized several indibulin-related diarylpyrrole derivatives and investigated their anti-cancer activity.
METHODS: Cell cultur studies were perfomred using the MTT cell viability assay on the breast cancer cell lines MCF-7, T47-D, and MDA-MB231 and also NIH-3 T3 cells as representative of a normal cell line. The activity of some of the synthesized compounds for tubulin interaction was studied using colchicine binding and tubulin polymerization assays. The annexin V-FITC/PI method and flow cytometric analysis were used for studying apoptosis induction and cell cycle distribution.
RESULTS AND CONCLUSION: Two of the synthesized compounds, 4f and 4 g, showed high activity on the MDA-MB231 cell line (IC50 = 11.82 and 13.33 μM, (respectively) and low toxicity on the normal fibroblast cells (IC50 > 100 μM). All of the tested compounds were more potent on T47-D cancer cells and less toxic on NIH-3 T3 normal cells in comparison to reference compound, indibulin. The tubulin polymerization inhibition assay and [3 H]colchicine binding assay showed that the main mechanism of cell death by the potent synthesized compounds was not related to an interaction with tubulin. In the annexin V/PI staining assay, the induction of apoptosis in the MCF-7 and MDA-MB231 cell lines was observed. Cell cycle analysis illustrated an increased percentage of sub-G-1 cells in the MDA-MB231 cell line as a further indication of cell death through induction of apoptosis. Graphical abstract Please provide Graphical abstract caption. Graphical abstract contains poor quality of text inside the artwork. Please do not re-use the file that we have rejected or attempt to increase its resolution and re-saveI changed the GA as new style. Please insert new version of GA as attached file.The following caption was provided for GA:Novel Indibulin analogous as anti-breast cancer agents. Novel Indibulin analogous as anti-breast cancer agents.
OBJECTIVES: With respect to need for finding potent and safe anticancer agents, in our current research work, we synthesized several indibulin-related diarylpyrrole derivatives and investigated their anti-cancer activity.
METHODS: Cell cultur studies were perfomred using the MTT cell viability assay on the breast cancer cell lines MCF-7, T47-D, and MDA-MB231 and also NIH-3 T3 cells as representative of a normal cell line. The activity of some of the synthesized compounds for tubulin interaction was studied using colchicine binding and tubulin polymerization assays. The annexin V-FITC/PI method and flow cytometric analysis were used for studying apoptosis induction and cell cycle distribution.
RESULTS AND CONCLUSION: Two of the synthesized compounds, 4f and 4 g, showed high activity on the MDA-MB231 cell line (IC50 = 11.82 and 13.33 μM, (respectively) and low toxicity on the normal fibroblast cells (IC50 > 100 μM). All of the tested compounds were more potent on T47-D cancer cells and less toxic on NIH-3 T3 normal cells in comparison to reference compound, indibulin. The tubulin polymerization inhibition assay and [3 H]colchicine binding assay showed that the main mechanism of cell death by the potent synthesized compounds was not related to an interaction with tubulin. In the annexin V/PI staining assay, the induction of apoptosis in the MCF-7 and MDA-MB231 cell lines was observed. Cell cycle analysis illustrated an increased percentage of sub-G-1 cells in the MDA-MB231 cell line as a further indication of cell death through induction of apoptosis. Graphical abstract Please provide Graphical abstract caption. Graphical abstract contains poor quality of text inside the artwork. Please do not re-use the file that we have rejected or attempt to increase its resolution and re-saveI changed the GA as new style. Please insert new version of GA as attached file.The following caption was provided for GA:Novel Indibulin analogous as anti-breast cancer agents. Novel Indibulin analogous as anti-breast cancer agents.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app