Self-Assembling Metallocomplexes of the Amphiphilic 1,4-Diazabicyclo[2.2.2]octane Derivative as a Platform for the Development of Nonplatinum Anticancer Drugs

Lucia Ya Zakharova; Alexandra D Voloshina; Marina R Ibatullina; Elena P Zhiltsova; Svetlana S Lukashenko; Darya A Kuznetsova; Marianna P Kutyreva; Anastasiia S Sapunova; Anna A Kufelkina; Natalia V Kulik; Olga Kataeva; Kamil A Ivshin; Aidar T Gubaidullin; Vadim V Salnikov; Irek R Nizameev; Marsil K Kadirov; Oleg G Sinyashin

doi:10.1021/acsomega.1c06465

Self-Assembling Metallocomplexes of the Amphiphilic 1,4-Diazabicyclo[2.2.2]octane Derivative as a Platform for the Development of Nonplatinum Anticancer Drugs

ACS Omega. 2022 Jan 14;7(3):3073-3082. doi: 10.1021/acsomega.1c06465. eCollection 2022 Jan 25.

Authors

Lucia Ya Zakharova¹, Alexandra D Voloshina¹, Marina R Ibatullina², Elena P Zhiltsova¹, Svetlana S Lukashenko¹, Darya A Kuznetsova¹, Marianna P Kutyreva², Anastasiia S Sapunova¹, Anna A Kufelkina¹, Natalia V Kulik¹, Olga Kataeva¹, Kamil A Ivshin², Aidar T Gubaidullin¹, Vadim V Salnikov³, Irek R Nizameev¹, Marsil K Kadirov¹, Oleg G Sinyashin¹

Affiliations

¹ Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, Kazan 420088, Russia.
² A.M. Butlerov Chemistry Institute, Kazan Federal University, Kremlevskaya Str. 18, Kazan 420008, Russia.
³ Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, Lobachevsky Street 2/31, Kazan 420111, Russia.

Abstract

New 1-cetyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide complexes with copper(II) bromide and lanthanum(III) nitrate were characterized using dynamic light scattering and transmission electron microscopy, with self-assembly and the morphological behavior elucidated. For the lanthanum(III) nitrate complex, the 3D crystal structure was characterized using X-ray diffractometry. These metallosurfactants were tested as antitumor agents, and a high cytotoxic effect comparable with doxorubicin was revealed against the M-HeLa and A-549 cell lines. Both complexes were 2 times more active toward the MCF-7 cell line than the breast cancer drug tamoxifen. The cytotoxic mechanism of complexes is assumed to be related to the induction of apoptosis through the mitochondrial pathway.