Synthesis, Characterization, and Cytotoxicity Studies of N-(4-Methoxybenzyl) Thiosemicarbazone Derivatives and Their Ruthenium(II)-p-cymene Complexes

Abstract

The reaction of [Ru2Cl2(μ-Cl)2(η6-p-cymene)2] with two thiosemicarbazones obtained by the condensation of N-(4-methoxybenzyl) thiosemicarbazide and 1,4-hydroxy-3-methoxyphenyl)ethan-1-one (HL1) or 2-fluoro-4-hydroxybenzaldehyde (HL2) was studied. The cationic complexes of formula [RuCl(η6-p-cymene)(HL)]+ were isolated as solid chloride and trifluoromethylsulfate (TfO) salts. A study of the solid state and NMR spectra suggests the presence in the material of two isomers that differ in the configuration in the iminic bond, C2=N3, of the coordinated thiosemicarbazone in the triflate salts and only the E isomer in the chloride. An X-ray study of single crystals of the complexes supports this hypothesis. The thiosemicarbazone ligand coordinates with the ruthenium center through the iminic and sulfur atoms to form a five-membered chelate ring. Furthermore, the isolation of single crystals containing the thiosemicarbazonate complex [Ru2(μ-L2)2(η6-p-cymene)2]2+ suggests the easy labilization of the coordinated chloride in the complex. The redox behavior of the ligands and complexes was evaluated by cyclic voltammetry. It seems to be more difficult to oxidize the complex derived from HL1 than HL2. The ability of the complexes to inhibit cell growth against the NCI-H460, A549, and MDA-MB-231 lines was evaluated. The complexes did not show greater potency than cisplatin, although they did have greater efficacy, especially for the complex derived from HL1.

Unraveling the Anticancer Efficacy and Biomolecular Properties of Ru(II)-Arene Complexes of Pyrene-Based Thiosemicarbazone Ligands: A Comprehensive In Silico/In Vitro Exploration

“…The compounds, as mentioned earlier, exhibit notable cytotoxicity against the MDA-MB-231 and A459 cell lines; however, they were less cytotoxic than cisplatin. 17 These studies exemplify the promising anticancer potential of Ru(II)arene complexes of TSCs. Furthermore, researchers have also evaluated the bioactivity of substituted naphthenyl, and anthracenyl groups incorporated ligands in transition metalarene complexes.…”

“…Similarly, Martínez-Estévez et al have synthesized Ru­(II)-(η 6 - p -cymene) complexes of N -(4-methoxybenzyl) TSC derivatives. The compounds, as mentioned earlier, exhibit notable cytotoxicity against the MDA-MB-231 and A459 cell lines; however, they were less cytotoxic than cisplatin . These studies exemplify the promising anticancer potential of Ru­(II)-arene complexes of TSCs.…”

Synthesis of the chromone‐thiosemicarbazone scaffold as promising α‐glucosidase inhibitors: An in vitro and in silico approach toward antidiabetic drug design

“…Over the years, thiosemicarbazones have gained much interest due to their antiviral, antioxidant, antiparasitic, antimicrobial, anticancer, cytotoxic, anticonvulsant, and antidiabetic activities. [34][35][36] Thiosemicarbazone derivatives exhibit notable antidiabetic activity having exceptional inhibitory effects against α-glucosidase, dipeptidyl peptidase-4, α-amylase, aldose reductase (ALR2), aldehyde reductase (ALR1), and glycogen phosphorylase. [37][38][39] Studies have shown that thiosemicarbazones when connected with different heterocycles exhibit antidiabetic properties.…”