Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N(iPr)CH2CH2OH] for R=Ph, Cy and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways
The synthesis and characterisation of R3PAu[S2CN(iPr)CH2CH2OH], for R = Ph (1), Cy (2) and Et (3)4, is reported. Compounds 1–3 are cytotoxic against the doxorubicin-resistant breast cancer cell line, MCF-7R, with 1 exhibiting greater potency and cytotoxicity than either of doxorubicin and cisplatin....
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my.upm.eprints.295902015-12-07T08:55:15Z http://psasir.upm.edu.my/id/eprint/29590/ Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N(iPr)CH2CH2OH] for R=Ph, Cy and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways Jamaludin, Nazzatush Shimar Goh, Zheng Jie Cheah, Yoke Kqueen Ang, Kok Pian Sim, Jiun Horng Khoo, Chai Hoon Zainal Abidin, Mohd Fairuz Abdul Halim, Siti Nadiah Ng, Seik Weng Seng, Hoi Ling Tiekink, Edward Richard Tom The synthesis and characterisation of R3PAu[S2CN(iPr)CH2CH2OH], for R = Ph (1), Cy (2) and Et (3)4, is reported. Compounds 1–3 are cytotoxic against the doxorubicin-resistant breast cancer cell line, MCF-7R, with 1 exhibiting greater potency and cytotoxicity than either of doxorubicin and cisplatin. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis by 1, and necrosis by 2 and 3, are demonstrated, by both extrinsic and intrinsic pathways. Compound 1 activates the p53 gene, 2 activates only the p73 gene, whereas 3 activates both the p53 and p73 genes. Compounds 1 and 3 activate NF-κB, and each inhibits topoisomerase I. Elsevier 2013-09 Article PeerReviewed Jamaludin, Nazzatush Shimar and Goh, Zheng Jie and Cheah, Yoke Kqueen and Ang, Kok Pian and Sim, Jiun Horng and Khoo, Chai Hoon and Zainal Abidin, Mohd Fairuz and Abdul Halim, Siti Nadiah and Ng, Seik Weng and Seng, Hoi Ling and Tiekink, Edward Richard Tom (2013) Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N(iPr)CH2CH2OH] for R=Ph, Cy and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways. European Journal of Medicinal Chemistry, 67. pp. 127-141. ISSN 0223-5234; ESSN: 1768-3254 http://www.sciencedirect.com/science/article/pii/S0223523413004066 10.1016/j.ejmech.2013.06.038 |
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The synthesis and characterisation of R3PAu[S2CN(iPr)CH2CH2OH], for R = Ph (1), Cy (2) and Et (3)4, is reported. Compounds 1–3 are cytotoxic against the doxorubicin-resistant breast cancer cell line, MCF-7R, with 1 exhibiting greater potency and cytotoxicity than either of doxorubicin and cisplatin. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis by 1, and necrosis by 2 and 3, are demonstrated, by both extrinsic and intrinsic pathways. Compound 1 activates the p53 gene, 2 activates only the p73 gene, whereas 3 activates both the p53 and p73 genes. Compounds 1 and 3 activate NF-κB, and each inhibits topoisomerase I. |
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Jamaludin, Nazzatush Shimar Goh, Zheng Jie Cheah, Yoke Kqueen Ang, Kok Pian Sim, Jiun Horng Khoo, Chai Hoon Zainal Abidin, Mohd Fairuz Abdul Halim, Siti Nadiah Ng, Seik Weng Seng, Hoi Ling Tiekink, Edward Richard Tom |
spellingShingle |
Jamaludin, Nazzatush Shimar Goh, Zheng Jie Cheah, Yoke Kqueen Ang, Kok Pian Sim, Jiun Horng Khoo, Chai Hoon Zainal Abidin, Mohd Fairuz Abdul Halim, Siti Nadiah Ng, Seik Weng Seng, Hoi Ling Tiekink, Edward Richard Tom Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N(iPr)CH2CH2OH] for R=Ph, Cy and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways |
author_facet |
Jamaludin, Nazzatush Shimar Goh, Zheng Jie Cheah, Yoke Kqueen Ang, Kok Pian Sim, Jiun Horng Khoo, Chai Hoon Zainal Abidin, Mohd Fairuz Abdul Halim, Siti Nadiah Ng, Seik Weng Seng, Hoi Ling Tiekink, Edward Richard Tom |
author_sort |
Jamaludin, Nazzatush Shimar |
title |
Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N(iPr)CH2CH2OH] for R=Ph, Cy and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways |
title_short |
Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N(iPr)CH2CH2OH] for R=Ph, Cy and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways |
title_full |
Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N(iPr)CH2CH2OH] for R=Ph, Cy and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways |
title_fullStr |
Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N(iPr)CH2CH2OH] for R=Ph, Cy and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways |
title_full_unstemmed |
Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N(iPr)CH2CH2OH] for R=Ph, Cy and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways |
title_sort |
phosphanegold(i) dithiocarbamates, r3pau[sc(=s)n(ipr)ch2ch2oh] for r=ph, cy and et: role of phosphane-bound r substituents upon in vitro cytotoxicity against mcf-7r breast cancer cells and cell death pathways |
publisher |
Elsevier |
publishDate |
2013 |
url |
http://psasir.upm.edu.my/id/eprint/29590/ http://www.sciencedirect.com/science/article/pii/S0223523413004066 |
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1643829806317436928 |
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13.18916 |