Study on a Ru(III) complex containing picolinate with potent inhibition effect against melanoma cell line

Abstract

A ruthenium(III) complex formulated as [Ru(pyc)₃]·H₂O (where pyc is pyridine-2-carboxylate) was prepared through a one-pot reaction of pyridine-2,6-dicarboxylic acid and anhydrous ruthenium(III) chloride. Here, hydrothermal conditions led to decarboxylation from pyridine-2,6-dicarboxylic acid into pyridine-2-carboxylate. The compound was identified by spectroscopic methods and its crystal structure was determined by single-crystal X-ray diffraction. The cytotoxicity of the compounds was evaluated by MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay against three cancer cell lines containing a human melanoma (A375), a human non-small cell lung carcinoma (H1299), a human colon adenocarcinoma (HT29), and also one normal cell human foreskin fibroblast (HFF). A strong and selective inhibitory effect of the complex (IC₅₀ = 6.50 μM, viability inhibition = 67.12%) was exhibited toward A375 cells. The apoptosis through a mitochondrial pathway was suggested via reactive oxygen species (ROS) production and mitochondria membrane potential (MMP) collapse. The cytostatic effect of the complex in the A375 3 D spheroid model was depicted.

KEYWORDS:

• Ru(III) Complex
• X-ray crystal structure
• cytotoxicity
• reactive oxygen species production
• mitochondrion pathway

Supplementary data

CCDC674713 contains the supplementary crystallographic data for the complex. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ, UK; Fax: [phone]; or E-mail: [email protected].

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We gratefully acknowledge Vice Chancellery for Research and Technology, Kermanshah University of Medical Sciences for financial support (Grant No. 4000483).