TY - JOUR
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 - http://www.scopus.com/inward/record.url?scp=85106731308&partnerID=8YFLogxK
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 -
