Impact of the Metal Center and Leaving Group on the Anticancer Activity of Organometallic Complexes of Pyridine-2-carbothioamide

Abstract

RuII(cym)Cl (cym = η6-p-cymene) complexes of pyridinecarbothioamides have shown potential for development as orally active anticancer metallodrugs, underlined by their high selectivity towards plectin as the molecular target. In order to investigate the impact of the metal center on the anticancer activity and their physicochemical properties, the Os(cym), Rh- and Ir(Cp*) (Cp* = pentamethylcyclopentadienyl) analogues of the most promising and orally active compound plecstatin 2 were prepared and characterized by spectroscopic techniques and X-ray diffraction analysis. Dissolution in aqueous medium results in quick ligand exchange reactions; however, over time no further changes in the 1H NMR spectra were observed. The Rh- and Ir(Cp*) complexes were investigated for their reactions with amino acids, and while they reacted with Cys, no reaction with His was observed. Studies on the in vitro anticancer activity identified the Ru derivatives as the most potent, independent of their halido leaving group, while the Rh derivative was more active than the Ir analogue. This demonstrates that the metal center has a significant impact on the anticancer activity of the compound class.

Quantum Chemical Investigation on Hydrolysis of Orally Active Organometallic Ruthenium(II) and Osmium(II) Anticancer Drugs and Their Interaction with Histidine

“…These complexes comprise a monodentate chloride and bidentate PCA ligand, and a remaining site is occupied by the η 6 - p -cymene ( p -cym ) arene that stabilizes the low oxidation state and adopts a pseudo-octahedral geometry. The organometallic ruthenium­(II) and osmium­(II) PCA complexes demonstrate high stability in the acidic and proteolytic environment with significant lipophilicity that makes them suitable oral active anticancer drugs. − …”

Synthesis, Biological Evaluation, and SAR Studies of Varyingly Substituted 4-Thioflavonols

“…Onion, apple, green tea, and caper are dietary sources of flavonols [4]. They are biologically active and show many bioactive properties Open Journal of Medicinal Chemistry such as anticancer [5], antimicrobial [6], anti-inflammatory [7], and many other activities. Thioflavonols are Thio analogs of flavonols (3-hydroxy-2-(phenyl)-4H-chrome-4-thione) in which an S atom is substituted for an O atom at the 4 th position in the C ring.…”