Pyrazolate-Bridged PdCo and PdCu Complexes as Dual DNA-Binding and ROS-Driven Cytotoxic Agents
4 affiliations
- 1Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Leninsky Prosp. 31, GSP-1, 119991 Moscow, Russia.
- 2Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str., 32, 119991 Moscow, Russia.
- 3N.N. Blokhin National Medical Research Center of Oncology, Kashirskoe Shosse 23, 115522 Moscow, Russia.
- 4Peoples' Friendship University of Russia, Miklukho-Maklaya 6, 117198 Moscow, Russia.
Abstract
Heterometallic complexes offer a promising anticancer strategy owing to their simultaneous action on multiple biological targets. In this work, we report the synthesis and evaluation of the antitumor potential of two heterometallic pyrazolate-bridged complexes, [PdCo(phen)(µ-dmpz)2(OOCMe)2] (PdCo) and [PdCu(phen)(µ-dmpz)2(OOCMe)2] (PdCu) (phen = 1,10-phenanthroline, dmpz = 3,5-dimethylpyrazole). The complexes were comprehensively characterized using a combined spectroscopic and analytical approach, including single-crystal X-ray diffraction (SC-XRD), PXRD, FTIR, UV-Vis, and mass spectrometry, confirming their structural integrity in both solid state and solution. Their cytotoxicity was assessed in vitro against colon, A549 lung, and breast cancer cell lines, as well as normal human dermal fibroblasts. The complexes exhibited micromolar IC50 values with selectivity indices up to 7. Using circular dichroism (CD) and fluorescence spectroscopy, it was demonstrated that PdCo binds to DNA, with minor groove binding (Kd = 7.6 μM) being the preferred mode of interaction, dominating over intercalation (Kd = 26.1 μM). Molecular docking simulations confirmed that the dissociated [Pd(phen)(µ-dmpz)2] fragment is capable of binding to DNA. Furthermore, chemiluminescence assays revealed pronounced peroxidase-like and superoxide dismutase-like activities of PdCu and PdCo, implicating ROS-mediated oxidative stress as a second, complementary cytotoxic pathway. Collectively, these findings highlight the dual-action mechanism of the synthesized complexes, combining DNA targeting with ROS-mediated oxidative damage, positioning them as highly potent candidates for further anticancer development.
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BibTeX
@article{uvarova2026pyrazolatebridged,
title = {{Pyrazolate-Bridged PdCo and PdCu Complexes as Dual DNA-Binding and ROS-Driven Cytotoxic Agents}},
author = {Marina A Uvarova and Vitalia V Kulikova and Yaroslav V Kozmenko and Svetlana V Revtovich and Arina D Filippova and Maxim A Shmelev and Darina V Sokolova and Vadim S Pokrovsky and Alexandra P Kaverina and Pavel N Solyev and Igor L Eremenko},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209009},
url = {https://www.mdpi.com/1422-0067/27/20/9009},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pyrazolate-Bridged PdCo and PdCu Complexes as Dual DNA-Binding and ROS-Driven Cytotoxic Agents
AU - Marina A Uvarova
AU - Vitalia V Kulikova
AU - Yaroslav V Kozmenko
AU - Svetlana V Revtovich
AU - Arina D Filippova
AU - Maxim A Shmelev
AU - Darina V Sokolova
AU - Vadim S Pokrovsky
AU - Alexandra P Kaverina
AU - Pavel N Solyev
AU - Igor L Eremenko
PY - 2026
DA - 2026/10/11
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209009
UR - https://www.mdpi.com/1422-0067/27/20/9009
AB - Heterometallic complexes offer a promising anticancer strategy owing to their simultaneous action on multiple biological targets. In this work, we report the synthesis and evaluation of the antitumor potential of two heterometallic pyrazolate-bridged complexes, [PdCo(phen)(µ-dmpz)2(OOCMe)2] (PdCo) and [PdCu(phen)(µ-dmpz)2(OOCMe)2] (PdCu) (phen = 1,10-phenanthroline, dmpz = 3,5-dimethylpyrazole). The complexes were comprehensively characterized using a combined spectroscopic and analytical approach, including single-crystal X-ray diffraction (SC-XRD), PXRD, FTIR, UV-Vis, and mass spectrometry, confirming their structural integrity in both solid state and solution. Their cytotoxicity was assessed in vitro against colon, A549 lung, and breast cancer cell lines, as well as normal human dermal fibroblasts. The complexes exhibited micromolar IC50 values with selectivity indices up to 7. Using circular dichroism (CD) and fluorescence spectroscopy, it was demonstrated that PdCo binds to DNA, with minor groove binding (Kd = 7.6 μM) being the preferred mode of interaction, dominating over intercalation (Kd = 26.1 μM). Molecular docking simulations confirmed that the dissociated [Pd(phen)(µ-dmpz)2] fragment is capable of binding to DNA. Furthermore, chemiluminescence assays revealed pronounced peroxidase-like and superoxide dismutase-like activities of PdCu and PdCo, implicating ROS-mediated oxidative stress as a second, complementary cytotoxic pathway. Collectively, these findings highlight the dual-action mechanism of the synthesized complexes, combining DNA targeting with ROS-mediated oxidative damage, positioning them as highly potent candidates for further anticancer development.
SN - 1422-0067
ER -