Design and synthesis of coumarin-based organoselenium as a new hit for myeloprotection and synergistic therapeutic efficacy in adjuvant therapy

Abstract A newly designed organoselenium compound, methyl substituted umbelliferone selenocyanate (MUS), was synthesized as a primary hit against the myelotoxic activity of carboplatin. MUS was administered at 6 mg/kg b.wt, p.o. in concomitant and pretreatment schedules with carboplatin (12 mg/kg b....

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Autores principales:	Arup Ranjan Patra, Somnath Singha Roy, Abhishek Basu, Avishek Bhuniya, Arin Bhattacharjee, Subhadip Hajra, Ugir Hossain Sk, Rathindranath Baral, Sudin Bhattacharya
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1c8e2bdf391949c091109c468d6745fe
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spelling	oai:doaj.org-article:1c8e2bdf391949c091109c468d6745fe2021-12-02T15:07:46ZDesign and synthesis of coumarin-based organoselenium as a new hit for myeloprotection and synergistic therapeutic efficacy in adjuvant therapy10.1038/s41598-018-19854-52045-2322https://doaj.org/article/1c8e2bdf391949c091109c468d6745fe2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19854-5https://doaj.org/toc/2045-2322Abstract A newly designed organoselenium compound, methyl substituted umbelliferone selenocyanate (MUS), was synthesized as a primary hit against the myelotoxic activity of carboplatin. MUS was administered at 6 mg/kg b.wt, p.o. in concomitant and pretreatment schedules with carboplatin (12 mg/kg b.wt, i.p. for 10 days) in female Swiss albino mouse. MUS treatment reduced (P < 0.001) the percentage of chromosomal aberrations, micronuclei formation, DNA damage and apoptosis in murine bone marrow cells and also enhanced (P < 0.001) the bone marrow cell proliferation of the carboplatin-treated mice. These activities cumulatively restored the viable bone marrow cell count towards normalcy. Myeloprotection by MUS was achieved, in part, due to a significant reduction in the ROS/RNS formation and restoration of glutathione redox pool. Additionally, MUS synergistically enhanced the cytotoxicity of carboplatin against two human cancer cell lines (MCF-7 and Colo-205). Furthermore, MUS can effectively potentiate the antitumour activity of carboplatin against two murine cancers (Dalton’s Lymphoma and Sarcoma-180) in vivo. These preclinical findings clearly indicate that MUS can improve the therapeutic index of carboplatin and ensures more effective therapeutic strategy against cancer for clinical development.Arup Ranjan PatraSomnath Singha RoyAbhishek BasuAvishek BhuniyaArin BhattacharjeeSubhadip HajraUgir Hossain SkRathindranath BaralSudin BhattacharyaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arup Ranjan Patra Somnath Singha Roy Abhishek Basu Avishek Bhuniya Arin Bhattacharjee Subhadip Hajra Ugir Hossain Sk Rathindranath Baral Sudin Bhattacharya Design and synthesis of coumarin-based organoselenium as a new hit for myeloprotection and synergistic therapeutic efficacy in adjuvant therapy
description	Abstract A newly designed organoselenium compound, methyl substituted umbelliferone selenocyanate (MUS), was synthesized as a primary hit against the myelotoxic activity of carboplatin. MUS was administered at 6 mg/kg b.wt, p.o. in concomitant and pretreatment schedules with carboplatin (12 mg/kg b.wt, i.p. for 10 days) in female Swiss albino mouse. MUS treatment reduced (P < 0.001) the percentage of chromosomal aberrations, micronuclei formation, DNA damage and apoptosis in murine bone marrow cells and also enhanced (P < 0.001) the bone marrow cell proliferation of the carboplatin-treated mice. These activities cumulatively restored the viable bone marrow cell count towards normalcy. Myeloprotection by MUS was achieved, in part, due to a significant reduction in the ROS/RNS formation and restoration of glutathione redox pool. Additionally, MUS synergistically enhanced the cytotoxicity of carboplatin against two human cancer cell lines (MCF-7 and Colo-205). Furthermore, MUS can effectively potentiate the antitumour activity of carboplatin against two murine cancers (Dalton’s Lymphoma and Sarcoma-180) in vivo. These preclinical findings clearly indicate that MUS can improve the therapeutic index of carboplatin and ensures more effective therapeutic strategy against cancer for clinical development.
format	article
author	Arup Ranjan Patra Somnath Singha Roy Abhishek Basu Avishek Bhuniya Arin Bhattacharjee Subhadip Hajra Ugir Hossain Sk Rathindranath Baral Sudin Bhattacharya
author_facet	Arup Ranjan Patra Somnath Singha Roy Abhishek Basu Avishek Bhuniya Arin Bhattacharjee Subhadip Hajra Ugir Hossain Sk Rathindranath Baral Sudin Bhattacharya
author_sort	Arup Ranjan Patra
title	Design and synthesis of coumarin-based organoselenium as a new hit for myeloprotection and synergistic therapeutic efficacy in adjuvant therapy
title_short	Design and synthesis of coumarin-based organoselenium as a new hit for myeloprotection and synergistic therapeutic efficacy in adjuvant therapy
title_full	Design and synthesis of coumarin-based organoselenium as a new hit for myeloprotection and synergistic therapeutic efficacy in adjuvant therapy
title_fullStr	Design and synthesis of coumarin-based organoselenium as a new hit for myeloprotection and synergistic therapeutic efficacy in adjuvant therapy
title_full_unstemmed	Design and synthesis of coumarin-based organoselenium as a new hit for myeloprotection and synergistic therapeutic efficacy in adjuvant therapy
title_sort	design and synthesis of coumarin-based organoselenium as a new hit for myeloprotection and synergistic therapeutic efficacy in adjuvant therapy
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/1c8e2bdf391949c091109c468d6745fe
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Design and synthesis of coumarin-based organoselenium as a new hit for myeloprotection and synergistic therapeutic efficacy in adjuvant therapy

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