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 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.

SUBMITTER: Shi H 

PROVIDER: S-EPMC8361943 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature