Fluorescent organometallic rhodium(I) and ruthenium(II) metallodrugs with 4-ethylthio-1,8-naphthalimide ligands: Antiproliferative effects, cellular uptake and DNA-interaction

6533b81ffe1ef96bd127886f

RESEARCH PRODUCT

Fluorescent organometallic rhodium(I) and ruthenium(II) metallodrugs with 4-ethylthio-1,8-naphthalimide ligands: Antiproliferative effects, cellular uptake and DNA-interaction

Alessio Terenzi Ingo Ott Yasamin Dabiri Bernhard K. Keppler Wojciech Streciwilk Stefan Wölfl Xinlai Cheng Julia E. Bandow Pascal Prochnow Laura A. Hager

subject

Intercalation (chemistry)Fluorescent Dye Ligands 01 natural sciences Antineoplastic Agent chemistry.chemical_compound Neoplasms Drug Discovery Moiety Cell Death Bacterial Infections General Medicine Intercalating Agents Naphthalimide Anti-Bacterial Agents Ruthenium Naphthalimides Settore CHIM/03 - Chimica Generale E Inorganica Human Stereochemistry chemistry.chemical_element Antineoplastic Agents Ligand Carbene 010402 general chemistry G-quadruplex Bacterial Infection Ruthenium Rhodium Cell Line Tumor Anti-Bacterial Agent Organometallic Compounds G-Quadruplexe Humans Rhodium Bioorganometallic Fluorescent Dyes Group 2 organometallic chemistry Cell Proliferation Pharmacology Organometallic Compound Bacteria 010405 organic chemistry Ligand Organic Chemistry Intercalating Agent 0104 chemical sciences G-Quadruplexes chemistry Neoplasm Drug Screening Assays Antitumor Carbene

description

Fluorescent 4-ethylthio-1,8-naphthalimides containing rhodium(I) N-heterocyclic carbene (NHC) and ruthenium (II) NHC fragments were synthesised and evaluated for their antiproliferative effects, cellular uptake and DNA-binding activity. Both types of organometallics triggered ligand dependent efficient cytotoxic effects against tumor cells with the rhodium(I) NHC derivatives causing stronger effects than the ruthenium (II) NHC analogues. Antiproliferative effects could also be observed against several pathogenic Gram-positive bacterial strains, whereas the growth of Gram-negative bacteria was not substantially affected. Cellular uptake was confirmed by atomic absorption spectroscopy as well as by fluorescence microscopy indicating a general ligand dependent accumulation in the cells. An in-depth study on the interaction with DNA confirmed insertion of the naphthalimide moiety between the planar bases of B-DNA via an intercalation mechanism, as well as its stacking on top of the quartets of G-quadruplex structures. Furthermore, additional coordinative binding of the organometallic complexes to the model DNA base 9-ethylguanine could be detected. The studied compounds thus represent promising bioorganometallics featuring strong pharmacological effects in combination with excellent cellular imaging properties.

year	journal	country	edition	language
2018-08-01

10.1016/j.ejmech.2018.06.056 http://hdl.handle.net/10447/392774