Metal Binding Characteristics of Heterocyclic and Carbocyclic Anticancer Drugs
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University of Toledo Health Science Campus / OhioLINK
2016
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=mco1481287656969232 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-mco14812876569692322021-08-03T06:39:23Z Metal Binding Characteristics of Heterocyclic and Carbocyclic Anticancer Drugs Bezoski, Brittany A. Pharmacy Sciences For decades, the anthracyclines such as doxorubicin, have been among the most common and effective group of antineoplastic drugs. Unfortunately, their use has been limited by their serious and irreparable cardiotoxicity, as a side effect. This damage to the heart was believed to be due to the drugs’ interactions with Fe2+. Investigators began to develop analogs in hope to reduce the cardiotoxic effects but retain the anticancer activity, and were successful in developing mitoxantrone and pixantrone. Pixantrone was developed to primarily replace the anthracylines, as it displayed broader spectrum of activity and lower toxicity. Further drug development resulted in another analog, BBR-3378, in the hope of further increasing the anticancer activity and reducing the cardiotoxicity. To investigate whether the harmful side effects of the drugs are specifically caused by the interaction with iron, interactions of doxorubicin, mitoxantrone, pixantrone, and BBR-3378 with iron were tested and compared with the drugs’ interactions with other metals, including copper and zinc, using spectroscopy as a readout. Doxorubicin and mitoxantrone appeared to interact with iron, whereas pixantrone and BBR-3378 did not. However, all of the four drugs interacted with zinc and copper, but copper interactions with the drugs were interrupted by the addition of albumin. The finding that doxorubicin and mitoxantrone interact with iron, but pixantrone does not, supports the role of iron in the contribution to the anthracycline-induced cardiotoxicity. And the fact that BBR-3387, does not seem to interact with iron, makes it a promising candidate for further studies to test its anticancer activity. Also, the finding that there is no distinction in the interactions of all of the drugs whether they are cardiotoxic or not, with other metals like copper and zinc may indicate that those metals may not contribute to the drugs’ toxicity. This might be further supported by the finding that the interaction of copper with drugs in the presence of albumin was interrupted, which may normally happen in natural bodily functions. 2016 English text University of Toledo Health Science Campus / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=mco1481287656969232 http://rave.ohiolink.edu/etdc/view?acc_num=mco1481287656969232 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Pharmacy Sciences |
| spellingShingle |
Pharmacy Sciences Bezoski, Brittany A. Metal Binding Characteristics of Heterocyclic and Carbocyclic Anticancer Drugs |
| author |
Bezoski, Brittany A. |
| author_facet |
Bezoski, Brittany A. |
| author_sort |
Bezoski, Brittany A. |
| title |
Metal Binding Characteristics of Heterocyclic and Carbocyclic Anticancer Drugs |
| title_short |
Metal Binding Characteristics of Heterocyclic and Carbocyclic Anticancer Drugs |
| title_full |
Metal Binding Characteristics of Heterocyclic and Carbocyclic Anticancer Drugs |
| title_fullStr |
Metal Binding Characteristics of Heterocyclic and Carbocyclic Anticancer Drugs |
| title_full_unstemmed |
Metal Binding Characteristics of Heterocyclic and Carbocyclic Anticancer Drugs |
| title_sort |
metal binding characteristics of heterocyclic and carbocyclic anticancer drugs |
| publisher |
University of Toledo Health Science Campus / OhioLINK |
| publishDate |
2016 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=mco1481287656969232 |
| work_keys_str_mv |
AT bezoskibrittanya metalbindingcharacteristicsofheterocyclicandcarbocyclicanticancerdrugs |
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1719440934339346432 |