Effective Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 Based on Monoterpenoids as Potential Agents for Antitumor Therapy
- Авторлар: Chepanova A.1, Li-Zhulanov N.2,3, Sukhikh A.3,4, Zafar A.5, Reynisson J.6, Zakharenko A.1, Zakharova O.1, Korchagina D.2, Volcho K.2,3, Salakhutdinov N.2,3, Lavrik O.1,3
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Мекемелер:
- Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences
- Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences
- Novosibirsk State University
- Nikolaev Institute of Inorganic Chemistry, Siberian Branch, Russian Academy of Sciences
- School of Chemical Sciences, University of Auckland
- School of Pharmacy, Keele University, Hornbeam Building
- Шығарылым: Том 45, № 6 (2019)
- Беттер: 647-655
- Бөлім: Article
- URL: https://journals.rcsi.science/1068-1620/article/view/229283
- DOI: https://doi.org/10.1134/S1068162019060104
- ID: 229283
Дәйексөз келтіру
Аннотация
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is one of the important DNA repair enzymes responsible for the repair of DNA damage caused by anticancer drugs, such as topotecan. In this regard, enzyme activity is one of the possible causes of tumor resistance to chemotherapy, and the use of inhibitors of this enzyme is considered as a promising adjuvant therapy. We have obtained a number of new isomeric naphthyl derivatives of thiophenyl octahydro-2H-chromene, the structure of one of which is confirmed by X-ray structural analysis. Based on molecular modeling data, the structure of the ligand-Tdp1 complex has been proposed. All compounds obtained inhibit Tdp1 at a concentration of about 2 μM. Low toxicity of three compounds was shown, which makes them promising candidates for the development of accompanying cancer therapy.
Негізгі сөздер
Авторлар туралы
A. Chepanova
Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences
Email: lavrik@niboch.nsc.ru
Ресей, Novosibirsk, 630090
N. Li-Zhulanov
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences; Novosibirsk State University
Email: lavrik@niboch.nsc.ru
Ресей, Novosibirsk, 630090; Novosibirsk, 630090
A. Sukhikh
Novosibirsk State University; Nikolaev Institute of Inorganic Chemistry, Siberian Branch, Russian Academy of Sciences
Email: lavrik@niboch.nsc.ru
Ресей, Novosibirsk, 630090; Novosibirsk, 630090
A. Zafar
School of Chemical Sciences, University of Auckland
Email: lavrik@niboch.nsc.ru
Жаңа Зеландия, Auckland, 1010
J. Reynisson
School of Pharmacy, Keele University, Hornbeam Building
Email: lavrik@niboch.nsc.ru
Ұлыбритания, Keele, Staffordshire, ST5 5BG
A. Zakharenko
Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences
Email: lavrik@niboch.nsc.ru
Ресей, Novosibirsk, 630090
O. Zakharova
Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences
Email: lavrik@niboch.nsc.ru
Ресей, Novosibirsk, 630090
D. Korchagina
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences
Email: lavrik@niboch.nsc.ru
Ресей, Novosibirsk, 630090
K. Volcho
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences; Novosibirsk State University
Email: lavrik@niboch.nsc.ru
Ресей, Novosibirsk, 630090; Novosibirsk, 630090
N. Salakhutdinov
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences; Novosibirsk State University
Email: lavrik@niboch.nsc.ru
Ресей, Novosibirsk, 630090; Novosibirsk, 630090
O. Lavrik
Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences; Novosibirsk State University
Хат алмасуға жауапты Автор.
Email: lavrik@niboch.nsc.ru
Ресей, Novosibirsk, 630090; Novosibirsk, 630090