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The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines
PURPOSE: Because of the scarcity of suitable brain cancer drugs, researchers are frantically trying to discover novel and highly potent drugs free of side effects and drug-resistance. Rhenium compounds are known to be nontoxic and exhibit no drug resistance. For that reason, we have developed a seri...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915335/ https://www.ncbi.nlm.nih.gov/pubmed/29707104 http://dx.doi.org/10.4172/1948-5956.1000512 |
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author | Banerjee, Hirendra N. Vaughan, Deidre Boston, Ava Thorne, Gabriel Payne, Gloria Sampson, Josiah Manglik, Vinod Olczak, Pola Powell, Brent V. Winstead, Angela Shaw, Roosevelt Mandal, Santosh K |
author_facet | Banerjee, Hirendra N. Vaughan, Deidre Boston, Ava Thorne, Gabriel Payne, Gloria Sampson, Josiah Manglik, Vinod Olczak, Pola Powell, Brent V. Winstead, Angela Shaw, Roosevelt Mandal, Santosh K |
author_sort | Banerjee, Hirendra N. |
collection | PubMed |
description | PURPOSE: Because of the scarcity of suitable brain cancer drugs, researchers are frantically trying to discover novel and highly potent drugs free of side effects and drug-resistance. Rhenium compounds are known to be nontoxic and exhibit no drug resistance. For that reason, we have developed a series of novel rhenium acetylsalicylato (RAC or ASP) complexes to test their cytotoxicity on brain cancer cells. Also we have attempted to explore the DNAbinding properties of these compounds because many drugs either directly or indirectly bind to DNA. METHODS: We have treated the RAC series compounds on human astrocytoma brain cancer cell lines and rat normal brain astrocyte cells and determined the efficacy of these complexes through in vitro cytotoxicity assay. We carried out the DNA-binding study through UV titrations of a RAC compound with DNA. Also we attempted to determine the planarity of the polypyridyl ligands of the RAC series compounds using DFT calculations. RESULTS: RAC6 is more potent than any other RAC series compounds on HTB-12 human astrocytoma cancer cells as well as on Glioblastoma Multiforme D54 cell lines. In fact, The IC-50 value of RAC6 on HTB-12 cancer cells is approximately 2 μM. As expected, the RAC series compounds were not active on normal cells. The DFT calculations on the RAC series compounds were done and suggest that the polypyridyl ligands in the complexes are planar. The UV-titrations of RAC9 with DNA were carried out. It suggests that RAC9 and possibly all RAC series compounds bind to minor grooves of the DNA. CONCLUSION: Because of the very low activity of RAC6 on normal cells and low lC(50) value of on astrocytoma (HTB-12) cell lines, it is possible that RAC6 and its derivatives may potentially find application in the treatment of brain cancers. The DFT calculations and UV titrations suggest that RAC series compounds either bind to DNA intercalatively or minor grooves of the DNA or both. However, it is highly premature to make any definite statement in the absence of other techniques. |
format | Online Article Text |
id | pubmed-5915335 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
record_format | MEDLINE/PubMed |
spelling | pubmed-59153352018-04-24 The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines Banerjee, Hirendra N. Vaughan, Deidre Boston, Ava Thorne, Gabriel Payne, Gloria Sampson, Josiah Manglik, Vinod Olczak, Pola Powell, Brent V. Winstead, Angela Shaw, Roosevelt Mandal, Santosh K J Cancer Sci Ther Article PURPOSE: Because of the scarcity of suitable brain cancer drugs, researchers are frantically trying to discover novel and highly potent drugs free of side effects and drug-resistance. Rhenium compounds are known to be nontoxic and exhibit no drug resistance. For that reason, we have developed a series of novel rhenium acetylsalicylato (RAC or ASP) complexes to test their cytotoxicity on brain cancer cells. Also we have attempted to explore the DNAbinding properties of these compounds because many drugs either directly or indirectly bind to DNA. METHODS: We have treated the RAC series compounds on human astrocytoma brain cancer cell lines and rat normal brain astrocyte cells and determined the efficacy of these complexes through in vitro cytotoxicity assay. We carried out the DNA-binding study through UV titrations of a RAC compound with DNA. Also we attempted to determine the planarity of the polypyridyl ligands of the RAC series compounds using DFT calculations. RESULTS: RAC6 is more potent than any other RAC series compounds on HTB-12 human astrocytoma cancer cells as well as on Glioblastoma Multiforme D54 cell lines. In fact, The IC-50 value of RAC6 on HTB-12 cancer cells is approximately 2 μM. As expected, the RAC series compounds were not active on normal cells. The DFT calculations on the RAC series compounds were done and suggest that the polypyridyl ligands in the complexes are planar. The UV-titrations of RAC9 with DNA were carried out. It suggests that RAC9 and possibly all RAC series compounds bind to minor grooves of the DNA. CONCLUSION: Because of the very low activity of RAC6 on normal cells and low lC(50) value of on astrocytoma (HTB-12) cell lines, it is possible that RAC6 and its derivatives may potentially find application in the treatment of brain cancers. The DFT calculations and UV titrations suggest that RAC series compounds either bind to DNA intercalatively or minor grooves of the DNA or both. However, it is highly premature to make any definite statement in the absence of other techniques. 2018-02-26 2018 /pmc/articles/PMC5915335/ /pubmed/29707104 http://dx.doi.org/10.4172/1948-5956.1000512 Text en http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Article Banerjee, Hirendra N. Vaughan, Deidre Boston, Ava Thorne, Gabriel Payne, Gloria Sampson, Josiah Manglik, Vinod Olczak, Pola Powell, Brent V. Winstead, Angela Shaw, Roosevelt Mandal, Santosh K The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines |
title | The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines |
title_full | The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines |
title_fullStr | The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines |
title_full_unstemmed | The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines |
title_short | The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines |
title_sort | effects of synthesized rhenium acetylsalicylate compounds on human astrocytoma cell lines |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915335/ https://www.ncbi.nlm.nih.gov/pubmed/29707104 http://dx.doi.org/10.4172/1948-5956.1000512 |
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