DNA-Intercalative Platinum Anticancer Complexes Photoactivated by Visible Light

Huayun Shi, Jana Kasparkova, Clément Soulié, Guy J. Clarkson, Cinzia Imberti, Olga Novakova, Martin J. Paterson, Viktor Brabec, Peter J. Sadler

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
28 Downloads (Pure)

Abstract

Photoactivatable agents offer the prospect of highly selective cancer therapy with low side effects and novel mechanisms of action that can combat current drug resistance. 1,8-Naphthalimides with their extended π system can behave as light-harvesting groups, fluorescent probes and DNA intercalators. We conjugated N-(carboxymethyl)-1,8-naphthalimide (gly-R-Nap) with an R substituent on the naphthyl group to photoactive diazido PtIV complexes to form t,t,t-[Pt(py)2(N3)2(OH)(gly-R-Nap)], R=H (1), 3-NO2 (2) or 4-NMe2 (3). They show enhanced photo-oxidation, cellular accumulation and promising photo-cytotoxicity in human A2780 ovarian, A549 lung and PC3 prostate cancer cells with visible light activation, and low dark cytotoxicity. Complexes 1 and 2 exhibit pre-intercalation into DNA, resulting in enhanced photo-induced DNA crosslinking. Complex 3 has a red-shifted absorption band at 450 nm, allowing photoactivation and photo-cytotoxicity with green light.
Original languageEnglish
Pages (from-to)10711-10716
Number of pages6
JournalChemistry - A European Journal
Volume27
Issue number41
Early online date27 May 2021
DOIs
Publication statusPublished - 21 Jul 2021

Keywords

  • anticancer activity
  • DFT calculations
  • DNA intercalation
  • interstrand crosslinking
  • photoactive platinum complexes

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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