Anticancer metallopharmaceutical agents based on mixed‐ligand palladium(II) complexes with dithiocarbamates and tertiary organophosphine ligands

Abstract

Mixed-ligand palladium(II) complexes of the type [(DT)Pd(PR 3 )Cl], where DT = diethyldithiocarbamate (1), dibutyldithiocarbamate (2,3), dipropyldithiocarbamate (4,5), bis(2-methoxyethyl)dithiocarbamate; PR 3 = benzyldiphenylphosphine (1,4), diphenyl-otolylphosphine (2), diphenyl-t-butylphosphine (3), P-chlorodiphenylphosphine (5) and triphenylphosphine (6), have been synthesized and characterized by elemental analyses and FT-IR, Raman and multinuclear NMR spectroscopy. The structures of compounds 1 and 2 were determined by single-crystal X-ray diffraction (XRD) measurements and these analyses showed that the complexes have pseudo square-planar geometry around the Pd(II) and that the dithiocarbamate ligand is bound in a bidentate fashion, while the remaining two positions are occupied by a tertiary organophosphine and a chloride ligand. The anticancer studies showed that the Pd(II) complexes are highly active against cisplatin-resistant DU145 human prostate carcinoma (HTB-81) cells with the highest activity shown by compound 6 (IC 50 = 2.12 mM). The redox behavior and ds-DNAdenaturing ability of the complexes were studied by cyclic voltammetry and two reduction and one oxidation waves were observed. The decrease in the reduction peak currents illustrated the consumption of the mixed-ligand drug by the DNA molecule.

New heteroleptic palladium(II) dithiocarbamates: synthesis, characterization, packing and anticancer activity against five different cancer cell lines

“…No significant change is observed except for the CS 2 carbon chemical shift which moves upfield from 214.6 ppm (ligand) to 206.4 ppm ( 1 ) and 206.7 ppm ( 2 ). This upfield shift of about 8 ppm upon complexation with Pd(II) can be attributed to an increase in the electron density on 1,1‐dithioate carbon due to the mobilization of the nitrogen lone pair electron of NCSS towards CSS moiety; these observations are in accord with higher stretching frequency values of the NC bond . This upfield shift supports the coordination of ligands with Pd(II) ion through sulfur atoms .…”

“…For the treatment of cancer, cisplatin is considered the best of a class of metallo‐drugs that have been used clinically for more than 40 years . Mechanistically, the anticancer action of cisplatin stems from its binding to N‐7 atom of guanine located in the major groove of the double helix of DNA . This cisplatin binding is responsible for arresting DNA replication, which finally leads to death of the cancer cell via apoptosis, necrosis, or both.…”

Crystal structures and Hirshfeld surface analyses of bis[N,N-bis(2-methoxyethyl)dithiocarbamato-κ2S,S′]di-n-butyltin(IV) and [N-(2-methoxyethyl)-N-methyldithiocarbamato-κ2S,S′]triphenyltin(IV)

“…Organotin dithiocarbamates have long been known to possess biological activity, in particular as anti-tumour and antibacterial agents (Tiekink, 2008). In keeping with the aforementioned, several recent studies have appeared investigating the biological activity of metal dithiocarbamates where the ligand contains at least one 2-methoxyethyl substituent (Khan et al, 2013(Khan et al, , 2016, including anti-bacterial potential of organotins (Mohamad, Awang, Kamaludin & Abu Bakar, 2016;. The latter ISSN 2056-9890 studies have been augmented by several structural investigations in recent times Mohamad, Awang, Kamaludin, Jotani et al, 2016;Mohamad et al, 2017).…”

Fabrication of PEI grafted Fe3O4/SiO2/P(GMA-co-EGDMA) nanoparticle anchored palladium nanocatalyst and its application in Sonogashira cross-coupling reactions

“…Simultaneously, the high stability is also demanded, which can effectively reduce the loss of palladium catalyst during the reaction process. Furthermore, some researches and our previous studies have shown that the ligands on the supports also show an important role in improving the catalytic activity of the supported catalyst [18][19][20][21][22]. In recent years, the fabrication and application of the branched organic segments grafted materials have became a very hot research topic, and these materials have been widely applied in drug delivery system, adsorption, catalysis, photonics, imprinting and so on for the unique spatial conformation and a large number of functional groups of the branched organic segments [23][24][25][26][27][28][29][30][31][32].…”