DNA-intercalative platinum anticancer complexes photoactivated by visible light.

Časopis: Chemistry - A European Journal
Autoři: Shi, H., Kasparkova, J., Soulié, C., Clarkson, G. J., Imberti, C., Novakova, O., Paterson, M. J., Brabec, V., Sadler, P. J.
Rok: 2021

Abstrakt

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.

http://wrap.warwick.ac.uk/153506/1/WRAP-DNA%E2%80%90intercalative-platinum-anticancer-complexes-photoactivated-visible-light-Shi-2021.pdf