Antitumor Activity and Reductive Stress by Platinum(II) N-Heterocyclic Carbenes based on Guanosine.

Autor: Leitão MIPS; Instituto de Tecnologia Química e Biológica António Xavier, Avd República, 2780-157, Oeiras, Portugal., Turos-Cabal M; Facultad de Medicina, Dpto. Morfología y Biología Celular, Universidad de Oviedo- Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), C/ Julián Clavería 6, 33006, Oviedo, Asturias, España., Sanchez-Sanchez AM; Facultad de Medicina, Dpto. Morfología y Biología Celular, Universidad de Oviedo- Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), C/ Julián Clavería 6, 33006, Oviedo, Asturias, España., Gomes CSB; LAQV-REQUIMTE, Department of Chemistry. Associate Laboratory i4 HB, NOVA Faculdade de Ciências e Tecnologias, Universidade Nova de Lisboa, 2829-516, Caparica, Portugal.; Institute for Health and Bioeconomy. UCIBIO, NOVA Faculdade de Ciências e Tecnologias, Universidade Nova de Lisboa, 2829-516, Caparica, Portugal.; Applied Molecular Biosciences Unit, Department of Chemistry, NOVA Faculdade de Ciências e Tecnologias, Universidade Nova de Lisboa, 2829-516, Caparica, Portugal., Herrera F; BioISI - Instituto de Biosistemas e Ciências integrativas, Dep. Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisboa, Portugal., Martin V; Facultad de Medicina, Dpto. Morfología y Biología Celular, Universidad de Oviedo- Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), C/ Julián Clavería 6, 33006, Oviedo, Asturias, España., Petronilho A; Instituto de Tecnologia Química e Biológica António Xavier, Avd República, 2780-157, Oeiras, Portugal.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2023 Jul 14; Vol. 29 (40), pp. e202301078. Date of Electronic Publication: 2023 May 30.
DOI: 10.1002/chem.202301078
Abstrakt: Platinum(II) complexes bearing N-heterocyclic carbenes based guanosine and caffeine have been synthesized by unassisted C-H oxidative addition, leading to the corresponding trans-hydride complexes. Platinum guanosine derivatives bearing triflate as counterion or bromide instead of hydride as co-ligand were also synthesized to facilitate correlation between structure and activity. The hydride compounds show high antiproliferative activity against all cell lines (TC-71, MV-4-11, U-937 and A-172). Methyl Guanosine complex 3, bearing a hydride ligand, is up to 30 times more active than compound 4, with a bromide in the same position. Changing the counterion has no significant effect in antiproliferative activity. Increasing bulkiness at N7, with an isopropyl group (compound 6), allows to maintain the antiproliferative activity while decreasing toxicity for non-cancer cells. Compound 6 leads to an increase in endoplasmic reticulum and autophagy markers on TC71 and MV-4-11 cancer cells, induces reductive stress and increases glutathione levels in cancer cells but not in non-cancer cell line HEK-293.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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