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Iodide analogs of arsenoplatins - potential drug candidates for triple negative breast cancers

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2021
osnovni rad (1.859Mb)
Authors
Miodragović, Ðenana
Qiang, Wenan
Waxali, Zohra Sattar
Vitnik, Željko
Vitnik, Vesna
Yang, Yi
Farrell, Annie
Martin, Matthew
Ren, Justin
O’Halloran, Thomas V.
Article (Published version)
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Abstract
Patients with triple negative breast cancers (TNBCs)—highly aggressive tumors that do not express estrogen, progesterone, and human epidermal growth factor 2 receptors—have limited treatment options. Fewer than 30% of women with metastatic TNBC survive five years after their diagnosis, with a mortality rate within three months after a recurrence of 75%. Although TNBCs show a higher response to platinum therapy compared to other breast cancers, drug resistance remains a major obstacle; thus, platinum drugs with novel mechanisms are urgently needed. Arsenoplatins (APs) represent a novel class of anticancer agents designed to contain the pharmacophores of the two FDA approved drugs cisplatin and arsenic trioxide (As2O3) as one molecular entity. Here, we present the syntheses, crystal structures, DFT calculations, and antiproliferative activity of iodide analogs of AP-1 and AP-2, i.e., AP-5 and AP-4, respectively. Antiproliferative studies in TNBC cell lines reveal that all AP family membe...rs are more potent than cisplatin and As2O3 alone. DFT calculations demonstrate there is a low energy barrier for hydrolysis of the platinum-halide bonds in arsenoplatins, possibly contributing to their higher cytotoxicities compared to cisplatin.

Keywords:
Antiproliferative activity / Arsenic trioxide / Arsenoplatin / Cisplatin / DFT / Triple negative breast cancers / X-ray structure
Source:
Molecules, 2021, 26, 17, 5421-
Publisher:
  • MDPI
Funding / projects:
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200026 (University of Belgrade, Institute of Chemistry, Technology and Metallurgy - IChTM) (RS-200026)

DOI: 10.3390/molecules26175421

ISSN: 1420-3049

WoS: 000694311100001

Scopus: 2-s2.0-85114603900
[ Google Scholar ]
2
URI
https://cer.ihtm.bg.ac.rs/handle/123456789/4766
Collections
  • Radovi istraživača / Researchers' publications
Institution/Community
IHTM
TY  - JOUR
AU  - Miodragović, Ðenana
AU  - Qiang, Wenan
AU  - Waxali, Zohra Sattar
AU  - Vitnik, Željko
AU  - Vitnik, Vesna
AU  - Yang, Yi
AU  - Farrell, Annie
AU  - Martin, Matthew
AU  - Ren, Justin
AU  - O’Halloran, Thomas V.
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4766
AB  - Patients with triple negative breast cancers (TNBCs)—highly aggressive tumors that do not express estrogen, progesterone, and human epidermal growth factor 2 receptors—have limited treatment options. Fewer than 30% of women with metastatic TNBC survive five years after their diagnosis, with a mortality rate within three months after a recurrence of 75%. Although TNBCs show a higher response to platinum therapy compared to other breast cancers, drug resistance remains a major obstacle; thus, platinum drugs with novel mechanisms are urgently needed. Arsenoplatins (APs) represent a novel class of anticancer agents designed to contain the pharmacophores of the two FDA approved drugs cisplatin and arsenic trioxide (As2O3) as one molecular entity. Here, we present the syntheses, crystal structures, DFT calculations, and antiproliferative activity of iodide analogs of AP-1 and AP-2, i.e., AP-5 and AP-4, respectively. Antiproliferative studies in TNBC cell lines reveal that all AP family members are more potent than cisplatin and As2O3 alone. DFT calculations demonstrate there is a low energy barrier for hydrolysis of the platinum-halide bonds in arsenoplatins, possibly contributing to their higher cytotoxicities compared to cisplatin.
PB  - MDPI
T2  - Molecules
T1  - Iodide analogs of arsenoplatins - potential drug candidates for triple negative breast cancers
VL  - 26
IS  - 17
SP  - 5421
DO  - 10.3390/molecules26175421
ER  - 
@article{
author = "Miodragović, Ðenana and Qiang, Wenan and Waxali, Zohra Sattar and Vitnik, Željko and Vitnik, Vesna and Yang, Yi and Farrell, Annie and Martin, Matthew and Ren, Justin and O’Halloran, Thomas V.",
year = "2021",
abstract = "Patients with triple negative breast cancers (TNBCs)—highly aggressive tumors that do not express estrogen, progesterone, and human epidermal growth factor 2 receptors—have limited treatment options. Fewer than 30% of women with metastatic TNBC survive five years after their diagnosis, with a mortality rate within three months after a recurrence of 75%. Although TNBCs show a higher response to platinum therapy compared to other breast cancers, drug resistance remains a major obstacle; thus, platinum drugs with novel mechanisms are urgently needed. Arsenoplatins (APs) represent a novel class of anticancer agents designed to contain the pharmacophores of the two FDA approved drugs cisplatin and arsenic trioxide (As2O3) as one molecular entity. Here, we present the syntheses, crystal structures, DFT calculations, and antiproliferative activity of iodide analogs of AP-1 and AP-2, i.e., AP-5 and AP-4, respectively. Antiproliferative studies in TNBC cell lines reveal that all AP family members are more potent than cisplatin and As2O3 alone. DFT calculations demonstrate there is a low energy barrier for hydrolysis of the platinum-halide bonds in arsenoplatins, possibly contributing to their higher cytotoxicities compared to cisplatin.",
publisher = "MDPI",
journal = "Molecules",
title = "Iodide analogs of arsenoplatins - potential drug candidates for triple negative breast cancers",
volume = "26",
number = "17",
pages = "5421",
doi = "10.3390/molecules26175421"
}
Miodragović, Ð., Qiang, W., Waxali, Z. S., Vitnik, Ž., Vitnik, V., Yang, Y., Farrell, A., Martin, M., Ren, J.,& O’Halloran, T. V.. (2021). Iodide analogs of arsenoplatins - potential drug candidates for triple negative breast cancers. in Molecules
MDPI., 26(17), 5421.
https://doi.org/10.3390/molecules26175421
Miodragović Ð, Qiang W, Waxali ZS, Vitnik Ž, Vitnik V, Yang Y, Farrell A, Martin M, Ren J, O’Halloran TV. Iodide analogs of arsenoplatins - potential drug candidates for triple negative breast cancers. in Molecules. 2021;26(17):5421.
doi:10.3390/molecules26175421 .
Miodragović, Ðenana, Qiang, Wenan, Waxali, Zohra Sattar, Vitnik, Željko, Vitnik, Vesna, Yang, Yi, Farrell, Annie, Martin, Matthew, Ren, Justin, O’Halloran, Thomas V., "Iodide analogs of arsenoplatins - potential drug candidates for triple negative breast cancers" in Molecules, 26, no. 17 (2021):5421,
https://doi.org/10.3390/molecules26175421 . .

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