Redox-Active Quinone Chelators: Properties, Mechanisms of Action, Cell Delivery, and Cell Toxicity

Redox-Active Quinone Chelators: Properties, Mechanisms of Action, Cell Delivery, and Cell Toxicity Full article

Journal

Antioxidants and Redox Signaling
ISSN: 1523-0864 , E-ISSN: 1557-7716

Output data

Year: 2018, Volume: 28, Number: 15, Pages: 1394-1403 Pages count : 10 DOI: 10.1089/ars.2017.7406

Tags

quinones; metals; ROS; photosensitizers; anticancer; cells

Authors

Polyakov Nikolay ¹ , Leshina Tatyana ¹ , Fedenok Lidiya ¹ , Slepneva Irina ¹ , Kirilyuk Igor ² , Furso Justyna ³ , Olchawa Magdalena ³ , Sarna Tadeusz ³ , Elas Martyna ³ , Bilkis Itzhak ⁴ , Weiner Lev ⁵

Affiliations

1	(Данные Web of science) Inst Chem Kinet & Combust, Novosibirsk, Russia
2	(Данные Web of science) Novosibirsk Organ Chem Inst, Lab Nitrogen Cpds, Novosibirsk, Russia
3	(Данные Web of science) Jagiellonian Univ, Dept Biophys, Krakow, Poland
4	(Данные Web of science) Hebrew Univ Jerusalem, Fac Agr Food & Environm, Inst Biochem, Rehovot, Israel
5	(Данные Web of science) Weizmann Inst Sci, Fac Biol, Dept Neurobiol, 234 Herzl St, IL-76100 Rehovot, Israel

Significance: Chemotherapy is currently the principal method for treating many malignancies. Thus, the development of improved antitumor drugs with enhanced efficacy and selectivity remains a high priority. Recent Advances: Anthracycline antibiotics (AAs), for example, doxorubicin, daunomycin, and mitomycin C, belong to an important family of antitumor agents widely used in chemotherapy. These compounds are all quinones. They are, thus, capable of being reduced by appropriate chemicals or reductases. One of their important properties is that under aerobic conditions their reduced forms undergo oxidation, with concomitant generation of reactive oxygen species (ROS), namely, superoxide anion radicals, hydrogen peroxide, and hydroxyl radicals. The presence of metal ions is essential for the generation of ROS by AAs in biological systems. Critical Issues: A fundamental shortcoming of the AAs is their high cardiotoxicity. We have proposed, and experimentally realized, a new type of quinones that is capable of coordinating metal ions. We have demonstrated in vitro that they can be reduced by electron transfer chains and glutathione with concomitant generation of ROS. They can also produce ROS under photo-excitation. The mechanisms of these reactions have been characterized by using nuclear magnetic resonance and electron paramagnetic resonance. Future Directions: To enhance their therapeutic effectiveness, and decrease cardiotoxicity and other side effects, we intend to conjugate the quinone chelators with monoclonal antibodies and peptide hormones that are specifically targeted to receptors on the cancer cell surface. Some such candidates have already been synthesized. An alternative approach for delivery of our compounds involves the use of specific peptide-based nanoparticles. In addition, our novel approach for treating malignancies is also suitable for photodynamic therapy.

Polyakov N. , Leshina T. , Fedenok L. , Slepneva I. , Kirilyuk I. , Furso J. , Olchawa M. , Sarna T. , Elas M. , Bilkis I. , Weiner L.
Redox-Active Quinone Chelators: Properties, Mechanisms of Action, Cell Delivery, and Cell Toxicity
Antioxidants and Redox Signaling. 2018. V.28. N15. P.1394-1403. DOI: 10.1089/ars.2017.7406 WOS Scopus РИНЦ

Published print:

May 20, 2018

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