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

doi:10.1002/chem.202101168

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 journal › Article › peer-review

30 Citations (Scopus)

94 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 Pt^IV 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 language	English
Pages (from-to)	10711-10716
Number of pages	6
Journal	Chemistry - A European Journal
Volume	27
Issue number	41
Early online date	27 May 2021
DOIs	https://doi.org/10.1002/chem.202101168
Publication status	Published - 21 Jul 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

anticancer activity
DFT calculations
DNA intercalation
interstrand crosslinking
photoactive platinum complexes

ASJC Scopus subject areas

Catalysis
Organic Chemistry

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@article{77c9a1c2a74d4ad9a479a702a2751e10,

title = "DNA-Intercalative Platinum Anticancer Complexes Photoactivated by Visible Light",

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.",

keywords = "anticancer activity, DFT calculations, DNA intercalation, interstrand crosslinking, photoactive platinum complexes",

author = "Huayun Shi and Jana Kasparkova and Cl{\'e}ment Souli{\'e} and Clarkson, \{Guy J.\} and Cinzia Imberti and Olga Novakova and Paterson, \{Martin J.\} and Viktor Brabec and Sadler, \{Peter J.\}",

note = "Funding Information: We acknowledge financial support from the EPSRC (EP/G006792, EP/F034210/1, P.J.S.; EP/P001459/1, EP/T021675/1, M.J.P.), Anglo‐American Platinum (post‐doctoral fellowship for H.S.), and Chancellor's International Scholarship from the University of Warwick (H.S.), and Czech Science Foundation (21‐27514S, J.K., O.N., and V.B.). This research was funded in part by the Wellcome Trust [Grant number 209173/Z/17/Z for CI]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Publisher Copyright: {\textcopyright} 2021 The Authors. Published by Wiley-VCH GmbH",

year = "2021",

month = jul,

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doi = "10.1002/chem.202101168",

language = "English",

volume = "27",

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journal = "Chemistry - A European Journal",

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T1 - DNA-Intercalative Platinum Anticancer Complexes Photoactivated by Visible Light

AU - Shi, Huayun

AU - Kasparkova, Jana

AU - Soulié, Clément

AU - Clarkson, Guy J.

AU - Imberti, Cinzia

AU - Novakova, Olga

AU - Paterson, Martin J.

AU - Brabec, Viktor

AU - Sadler, Peter J.

N1 - Funding Information: We acknowledge financial support from the EPSRC (EP/G006792, EP/F034210/1, P.J.S.; EP/P001459/1, EP/T021675/1, M.J.P.), Anglo‐American Platinum (post‐doctoral fellowship for H.S.), and Chancellor's International Scholarship from the University of Warwick (H.S.), and Czech Science Foundation (21‐27514S, J.K., O.N., and V.B.). This research was funded in part by the Wellcome Trust [Grant number 209173/Z/17/Z for CI]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Publisher Copyright: © 2021 The Authors. Published by Wiley-VCH GmbH

PY - 2021/7/21

Y1 - 2021/7/21

N2 - 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.

AB - 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.

KW - anticancer activity

KW - DFT calculations

KW - DNA intercalation

KW - interstrand crosslinking

KW - photoactive platinum complexes

UR - https://www.scopus.com/pages/publications/85106731308

U2 - 10.1002/chem.202101168

DO - 10.1002/chem.202101168

M3 - Article

C2 - 34046954

SN - 0947-6539

VL - 27

SP - 10711

EP - 10716

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 41

ER -

DNA-Intercalative Platinum Anticancer Complexes Photoactivated by Visible Light

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

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