On the medicinal chemistry of gold complexes as anticancer drugs

The chemistry of gold

New trends in platinum and palladium complexes as antineoplastic agents

Platinum compounds represent one of the great success stories of metals in medicine. Following the serendipitous discovery of the anticancer activity of cisplatin by Rosenberg, a large number of cisplatin variants have been prepared and tested for their ability to kill cancer cells and inhibit tumor growth. These efforts continue today with increased realization that new strategies are needed to overcome issues of toxicity and resistance inherent to treatment by the approved platinum anticancer agents. One approach has been the use of so-called “non-traditional” platinum(II) and platinum(IV) compounds that violate the structure–activity relationships that governed platinum drug-development research for many years. Another is the use of specialized drug-delivery strategies. Here we describe recent developments from our laboratory involving monofunctional platinum(II) complexes together with a historical account of the manner by which we came to investigate these compounds and their relationship to previous...

Monofunctional and Higher-Valent Platinum Anticancer Agents

Pt-doped mesoporous Ti3+ self-doped TiO2 (Pt–Ti3+/TiO2) is in situ synthesized via an ionothermal route, by treating metallic Ti in an ionic liquid containing LiOAc, HOAc, and a H2PtCl6 aqueous solution under mild ionothermal conditions. Such Ti3+-enriched environment, as well as oxygen vacancies, is proven to be effective for allowing the in situ reduction of Pt4+ ions uniformly located in the framework of the TiO2 bulk. The photocatalytic H2 evolution of Pt–Ti3+/TiO2 is significantly higher than that of the photoreduced Pt loaded on the original TiO2 and commercial P25. Such greatly enhanced activity is due to the various valence states of Pt (Ptn+, n = 0, 2, or 3), forming Pt–O bonds embedded in the framework of TiO2 and ultrafine Pt metal nanoparticles on the surface of TiO2. Such Ptn+–O bonds could act as the bridges for facilitating the photogenerated electron transfer from the bulk to the surface of TiO2 with a higher electron carrier density (3.11 × 1020 cm–3), about 2.5 times that (1.25 × 1020 cm...

Pt-Enhanced Mesoporous Ti3+/TiO2 with Rapid Bulk to Surface Electron Transfer for Photocatalytic Hydrogen Evolution.

Monomeric Pt(II) and Pd(II) complexes with Creatinine. Crystal structure of tetrakis-(Creatinine) platinum(II) diperchlorate

Structure of Ni(II)-creatinine complex species formed in non-aqueous media

Three stable mononuclear hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp) complexes of PtIII, namely cis-[ PtIII(NH3)2(Hp−3H)(H2O)2].H2O 1, [PtIII(Hp−3H)(H2O)2].H2O 2 and [PtIII((O,O)Hp−2H)Cl(H2O)3] 3 with distorted octahedral structure and (dz2)1 ground state have been tested in vitro for antineoplastic activity in a panel of tumor cell lines. The novel platinum(III) complexes showed cytotoxic activity in a concentration-dependent manner with IC50 values comparable to those of referent cytotoxic agent cisplatin together with lower cytotoxicity against renal cells. Further detailed evaluation of the active analogue 2 and the less active complex 3 showed that their potency greatly correlates with the ability to induce apoptosis and to bind DNA. Despite the structural dissimilarities between complex 2 and cisplatin, their DNA-adducts were equally effectively recognized and repaired by the nucleotide excision repair system. Complex 2 showed quite superior ability to accumulate in K-562 cells relative to cisplatin.

In vitro pharmacological study of monomeric platinum (III) hematoporphyrin IX complexes

Monomeric Au(II) complex with hematoporphyrin IX

Anti-cancer therapies that integrate smart nanomaterials are the focus of cancer research in recent years. Here, we present our results with PEGylated nanographene oxide particles (nGO-PEG) and have studied their combined effect with near-infrared (NIR) irradiation on low and high invasive colorectal carcinoma cells. The aim is to develop nGO-PEG as a smart nanocarrier for colon cancer-targeted therapy. For this purpose, nGO-PEG nanoparticles' size, zeta potential, surface morphology, dispersion stability, aggregation, and sterility were determined and compared with pristine nGO nanoparticles (NPs). Our results show that PEGylation increased the particle sizes from 256.7 nm (pristine nGO) to 324.6 nm (nGO-PEG), the zeta potential from -32.9 to -21.6 mV, and wrinkled the surface of the nanosheets. Furthermore, nGO-PEG exhibited higher absorbance in the NIR region, as compared to unmodified nGO. PEGylated nGO demonstrated enhanced stability in aqueous solution, improved dispensability in the culture medium, containing 10% fetal bovine serum (FBS) and amended biocompatibility. A strong synergic effect of nGO-PEG activated with NIR irradiation for 5 min (1.5 W/cm-2 laser) was observed on cell growth inhibition of low invasive colon cancer cells (HT29) and their wound closure ability while the effect of NIR on cellular morphology was relatively weak. Our results show that PEGylation of nGO combined with NIR irradiation holds the potential for a biocompatible smart nanocarrier in colon cancer cells with enhanced physicochemical properties and higher biological compatibility. For that reason, further optimization of the irradiation process and detailed screening of nGO-PEG in combination with NIR and chemotherapeutics on the fate of the colon cancer cells is a prerequisite for highly efficient combined nanothermal and photothermal therapy for colon cancer.

https://www.mdpi.com/1999-4923/13/3/424/pdf

G. Gencheva

Papers

Monomeric Pt(II) and Pd(II) complexes with Creatinine. Crystal structure of tetrakis-(Creatinine) platinum(II) diperchlorate

Structure of Ni(II)-creatinine complex species formed in non-aqueous media

In vitro pharmacological study of monomeric platinum (III) hematoporphyrin IX complexes

Monomeric Au(II) complex with hematoporphyrin IX

PEGylated Nanographene Oxide in Combination with Near-Infrared Laser Irradiation as a Smart Nanocarrier in Colon Cancer Targeted Therapy