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DNA‐Intercalative Platinum Anticancer Complexes Photoactivated by Visible Light
Author(s) -
Shi Huayun,
Kasparkova Jana,
Soulié Clément,
Clarkson Guy J.,
Imberti Cinzia,
Novakova Olga,
Paterson Martin J.,
Brabec Viktor,
Sadler Peter J.
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202101168
Subject(s) - cytotoxicity , chemistry , intercalation (chemistry) , visible spectrum , substituent , dna , fluorescence , nap , photochemistry , absorption (acoustics) , dna damage , a549 cell , stereochemistry , in vitro , biochemistry , organic chemistry , materials science , biology , physics , optoelectronics , quantum mechanics , neuroscience , composite material
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 Pt IV complexes to form t,t,t ‐[Pt(py) 2 (N 3 ) 2 (OH)(gly‐R‐Nap)], R=H ( 1 ), 3‐NO 2 ( 2 ) or 4‐NMe 2 ( 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.