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Chiral zinc complexes with terpene derivatives of ethylenediamine: synthesis and biological activity

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Russian Chemical Bulletin Aims and scope

Abstract

Six new chiral zinc(ii) complexes 1–6 based on ethylenediamine derivatives of terpenes were synthesized and characterized. The molecular structure of complex 2 was established by X-ray diffraction analysis. The modulating effect of complexes 1–6 on the functional state of mitochondria, which are organelles playing an utterly important role in maintaining the energy balance of cells, transfer of genetic material, and regulation of the processes of triggering the cell death by apoptosis, autophagy, and necrosis, was studied. It is shown that synthesized zinc complexes lead to depolarization of the mitochondrial membrane, an increase in the threshold of sensitivity of the organelles to calcium-induced opening of the mitochondrial permeability transition pores, and disruption of the operation of the respiratory chain complexes in these organelles. Such a dysfunctional state of mitochondria is one of the main causes of cell death through apoptosis due to the release of various proapoptotic factors into the intracellular space. In this regard, the newly synthesized zinc complexes 1–6 can be considered as destructive agents aimed at triggering cell death cascades by affecting mitochondrial functions. These properties are of paramount importance when searching for potential drugs with possible antitumor, antiprotozoal, or antifungal activity.

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Authors and Affiliations

  1. Institute of Chemistry, Komi Scientific Centre, Ural Branch of the Russian Academy of Sciences, 48 ul. Pervomayskaya, 167000, Syktyvkar, Russian Federation

    Y. A. Gur’eva, O. A. Zalevskaya & A. V. Kutchin

  2. Institute of Physiologically Active Compounds, Russian Academy of Sciences, 1 Severny proezd, 142432, Chernogolovka, Russian Federation

    N. S. Nikolaeva, Yu. R. Aleksandrova, E. Yu. Yandulova & M. E. Neganova

  3. I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of Russian Academy of Sciences, 22/20 ul. S. Kovalevskoi, 620108, Yekaterinburg, Russian Federation

    P. A. Slepukhin

Authors
  1. Y. A. Gur’eva
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  2. O. A. Zalevskaya
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  3. N. S. Nikolaeva
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  4. Yu. R. Aleksandrova
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  5. E. Yu. Yandulova
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Corresponding author

Correspondence to O. A. Zalevskaya.

Additional information

Based on the materials of the V Russian Conference on Medicinal Chemistry with international participation “MedChem-Russia 2021” (May 16–19, 2022, Volgograd, Russia).

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2612–2620, December, 2022.

Spectroscopic studies of zinc complexes were performed using the equipment of the Center of Collective Usage “Chemistry” of the Institute of Chemistry, Komi Scientifi c Center, Ural Branch of the Russian Academy of Sciences. X-ray diff raction analysis was performed on the equipment of the Center of Collective Usage “Spectroscopy and Analysis of Organic Compounds” of the Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences. All biological tests were carried out with the use of the equipment of the Center of Collective Usage of the Institute of Physiologically Active Substances of the Russian Academy of Sciences (IPAC RAS).

This work was performed under financial support of the Russian Foundation for Basic Research (Project No. 20-03-00027) and Ministry of Science and Higher Education of the Russian Federation (State task No. 122040600073-3).

The animals were kept under standard conditions in accordance with Directive 2010/63 EU of the European Parliament and of the Council of the European Union on the protection of animals used for scientific purposes dated September 22, 2010. All experiments with animals were carried out in compliance with international principles and norms in accordance with the decisions of the Commission on Biological Ethics of IPAC RAS (protocol No. 59 dated May 12, 2022).

The authors declare no competing interests.

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Gur’eva, Y.A., Zalevskaya, O.A., Nikolaeva, N.S. et al. Chiral zinc complexes with terpene derivatives of ethylenediamine: synthesis and biological activity. Russ Chem Bull 71, 2612–2620 (2022). https://doi.org/10.1007/s11172-022-3690-0

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