Iodide analogs of arsenoplatins - potential drug candidates for triple negative breast cancers
Authors
Miodragović, ÐenanaQiang, 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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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 structureSource:
Molecules, 2021, 26, 17, 5421-Publisher:
- MDPI
Funding / projects:
DOI: 10.3390/molecules26175421
ISSN: 1420-3049
WoS: 000694311100001
Scopus: 2-s2.0-85114603900
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IHTMTY - 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 . .