Header

UZH-Logo

Maintenance Infos

Photostable Platinated Bacteriochlorins as Potent Photodynamic Agents


Le, Ngoc An; Babu, Vipin; Kalt, Martina; Schneider, Lukas; Schumer, Frank; Spingler, Bernhard (2021). Photostable Platinated Bacteriochlorins as Potent Photodynamic Agents. Journal of Medicinal Chemistry, 64(10):6792-6801.

Abstract

Photodynamic therapy (PDT) is used to treat various cancerous diseases. Recently, we have demonstrated that platinated pyridyl-substituted porphyrins are potent agents for PDT with very high phototoxicity (IC50 down to 17 nM) and excellent phototoxic indices of higher than 5800 (p.i. = IC50(dark)/IC50(light)) [Rubbiani, R. et al., Chem. Commun. 2020, 56, 14373]. However, the absorption of porphyrins is not ideal for the treatment of larger tumors because they essentially do not absorb light between 650 and 850 nm. Herein, we report stable conjugates of a novel bacteriochlorin with cisplatin and transplatin. They exhibit extremely high phototoxicity (IC50 values down to 6 nM, irradiated with a 750 nm LED at a fluence of 5 J/cm2), very low dark toxicity, and thereby extremely high phototoxic indices up to 8300. Based on these exciting results, we believe that platinated bacteriochlorins are promising candidates for further investigation as novel PDT anticancer agents.

Abstract

Photodynamic therapy (PDT) is used to treat various cancerous diseases. Recently, we have demonstrated that platinated pyridyl-substituted porphyrins are potent agents for PDT with very high phototoxicity (IC50 down to 17 nM) and excellent phototoxic indices of higher than 5800 (p.i. = IC50(dark)/IC50(light)) [Rubbiani, R. et al., Chem. Commun. 2020, 56, 14373]. However, the absorption of porphyrins is not ideal for the treatment of larger tumors because they essentially do not absorb light between 650 and 850 nm. Herein, we report stable conjugates of a novel bacteriochlorin with cisplatin and transplatin. They exhibit extremely high phototoxicity (IC50 values down to 6 nM, irradiated with a 750 nm LED at a fluence of 5 J/cm2), very low dark toxicity, and thereby extremely high phototoxic indices up to 8300. Based on these exciting results, we believe that platinated bacteriochlorins are promising candidates for further investigation as novel PDT anticancer agents.

Statistics

Citations

Dimensions.ai Metrics
17 citations in Web of Science®
17 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

68 downloads since deposited on 08 Jun 2021
35 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Life Sciences > Molecular Medicine
Life Sciences > Drug Discovery
Uncontrolled Keywords:Molecular Medicine, Drug Discovery
Language:English
Date:27 May 2021
Deposited On:08 Jun 2021 13:58
Last Modified:26 Mar 2024 02:36
Publisher:American Chemical Society (ACS)
ISSN:0022-2623
OA Status:Green
Publisher DOI:https://doi.org/10.1021/acs.jmedchem.1c00052
Project Information:
  • : FunderSNSF
  • : Grant ID206021_164018
  • : Project TitleDual X-ray Wavelength Single-Crystal Diffractometer
  • Content: Accepted Version
  • Language: English