DNA‐Intercalative Platinum Anticancer Complexes Photoactivated by Visible Light
Huayun Shi, Jana Kašpárková, Clément Soulié, Guy J. Clarkson, Cinzia Imberti, Olga Nováková, Martin J. Paterson, Viktor Brabec, Peter J. Sadler
Abstract
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 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.