Tridentate 3-Substituted Naphthoquinone Ruthenium Arene Complexes: Synthesis, Characterization, Aqueous Behavior, and Theoretical and Biological Studies

Abstract

A series of nine Ru II arene complexes bearing tridentate naphthoquinone-based N , O , O -ligands was synthesized and characterized. Aqueous stability and their hydrolysis mechanism were investigated via UV/vis photometry, HPLC-MS, and density functional theory calculations. Substituents with a positive inductive effect improved their stability at physiological pH (7.4) intensely, whereas substituents such as halogens accelerated hydrolysis and formation of dimeric pyrazolate and hydroxido bridged dimers. The observed cytotoxic profile is unusual, as complexes exhibited much higher cytotoxicity in SW480 colon cancer cells than in the broadly chemo- (incl. platinum-) sensitive CH1/PA-1 teratocarcinoma cells. This activity pattern as well as reduced or slightly enhanced ROS generation and the lack of DNA interactions indicate a mode of action different from established or previously investigated classes of metallodrugs.

Metal complexes of a pro-vitamin K3 analog phthiocol (2-hydroxy-3-methylnaphthalene-1,4-dione): synthesis, characterization, and anticancer activity

“…Among all the tested complexes, 2 and 3 exhibit superior action on mitochondria in both cell lines. A recent report by Geisler et al 23,66 documented the cytotoxic potential of the phthiocol-based ruthenium complex in vitro against three human cancer cell lines, namely A549 (non-small cell lung carcinoma), ASW480 (colon carcinoma), and CH1/PA-1 (ovarian teratocarcinoma).…”

Naphthoyl benzhydrazine–decorated binuclear arene Ru(ii) complexes as anticancer agents targeting human breast cancer cells

“…They disclosed that the substitution with a positive inductive effect enhanced the stability in the aqueous state and influenced the anticancer properties. 17…”

“…They disclosed that the substitution with a positive inductive effect enhanced the stability in the aqueous state and influenced the anticancer properties. 17 Consequentially, this work involved the construction and characterization of a new family of organometallic binuclear ruthenium(II) complexes featuring 4-substituted naphthoyl benzhydrazine ligands. The efficacy of Ru(II) arene complexes was assessed against three subtypes of breast cancer cells and non-cancer cells and compared with cisplatin.…”

Copper Complexes of 1,4-Naphthoquinone Containing Thiosemicarbazide and Triphenylphosphine Oxide Moieties; Synthesis and Identification by NMR, IR, Mass, UV Spectra, and DFT Calculations

“…This activity pattern, reduced or slightly enhanced ROS generation, and the lack of DNA interactions indicate a mode of action different from established or previously investigated classes of metallodrugs. 3 …”

“…This activity pattern, reduced or slightly enhanced ROS generation, and the lack of DNA interactions indicate a mode of action different from established or previously investigated classes of metallodrugs. 3 The reactions of 1,4-naphthoquinone with triphenylphosphine (Ph 3 P) have been previously described. As, for example, in the reaction of fluoronaphthoquinone (1) with triphenyl-phosphine (Ph 3 P), derivatives of phosphonium betaines derived from hexafluoro-1,4-naphthoquinone: (triphenyl- [5,6,7,8-tetrafluoro-1-oxido-4-oxo-3-(phenylimino)-3,4-dihydro-naphthalen-2-yl]phosphonium) 3 (Scheme 1), were obtained.…”