DNA‐Intercalative Platinum Anticancer Complexes Photoactivated by Visible Light
| Autor: | Clément Soulié, Jana Kasparkova, Cinzia Imberti, Viktor Brabec, Guy J. Clarkson, Huayun Shi, Martin J. Paterson, Olga Novakova, Peter J. Sadler |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Light
Organoplatinum Compounds interstrand crosslinking Substituent Antineoplastic Agents Conjugated system 010402 general chemistry DFT calculations 01 natural sciences Catalysis DNA intercalation chemistry.chemical_compound DNA Crosslinking Cell Line Tumor Humans QD Cytotoxicity Platinum Ovarian Neoplasms Full Paper 010405 organic chemistry Chemistry QH Organic Chemistry General Chemistry DNA Full Papers Fluorescence Combinatorial chemistry QP 0104 chemical sciences DNA Intercalation anticancer activity photoactive platinum complexes Female Visible spectrum RC |
| Zdroj: | Chemistry (Weinheim an Der Bergstrasse, Germany) |
| ISSN: | 1521-3765 0947-6539 |
| Popis: | 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. Green to go: Photoactive all‐trans diazido PtIV complexes with an axial 1,8‐naphthalimide ligand that can pre‐intercalate into DNA have been synthesised. They can be photoactivated with visible light to generate PtII DNA interstrand crosslinks and cytotoxic ROS, and are thus promising photo‐chemotherapeutic agents. Notably, a 4‐NMe2 substituent red‐shifted absorption of the naphthalimide ring, giving rise to its green‐light photo‐cytotoxicity. |
| Databáze: | OpenAIRE |
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