Metallodrugs as Anticancer Chemotherapeutics and Diagnostic Agents: A Critical Patent Review (2010-2020).

BACKGROUND: The development of metallodrugs with potential applications in cancer treatment and diagnosis has been a hot topic since the approval and subsequent marketing of the anticancer drug cisplatin in 1978. Since then, thousands of metal-based derivatives have been reported and evaluated for their chemotherapeutic or tumor imaging properties, but only a very limited number gained clinical status. Nonetheless, research in the field has been increasing exponentially over the years, especially in a view to exploiting novel drug designing approaches and strategies aimed at improving pharmacological outcomes and, at the same time, reducing side-effects. OBJECTIVES: This review article reports on the patents filed during the last decade and strictly focusing on the development of metal-based anticancer and diagnostic agents. The goal is to identify the latest trends and designing strategies in the field, which would represent a valuable starting point to researchers interested in the development of metallodrugs. METHODS: The most relevant patents filed in the 2010-2020 timeframe have been retrieved from various databases using dedicated search engines (such as SciFinder, Google Patents, PatentPak, Espacenet, Global Dossier, PatentScope), sorted by type of metallodrug and screened to include those reporting a substantial amount of biological data. RESULTS: The majority of patents here reviewed are concerned with metallodrugs (mostly platinum- based) showing interesting pharmacological properties but no specific tumor-targeting features. Nonetheless, some promising trends in the development of novel drug delivery strategies and/or metallodrugs with potential applications in targeted chemotherapy are envisaged. CONCLUSION: In this review, the latest trends in the development of metallodrugs from recent patents are summarized and critically discussed. Such trends would be of interest not only to the scientific community but also to lay audiences aiming to broaden their knowledge of the field and industrial stakeholders potentially interested in the exploitation and commercialization of this class of pharmaceuticals.

Design, physico-chemical characterization and in vitro biological activity of organogold(III) glycoconjugates.

To develop new metal-based glycoconjugates as potential anticancer agents, four organometallic gold(iii)-dithiocarbamato glycoconjugates of the type [AuIII(2-Bnpy)(SSC-Inp-GlcN)](PF6) (2-Bnpy: 2-benzylpyridine; Inp: isonipecotic moiety; GlcN: amino-glucose scaffold; Au3-Au6) and the corresponding model non-glycosylated counterparts [AuIII(2-Bnpy)(SSC-Inp-R)](PF6) (R: OEt (Au1), NH2 (Au2)) have been generated and characterized by means of several analytical techniques (elemental analysis, FT-IR, 1H-/13C-NMR, ESI-MS, UV-Vis, X-ray crystallography). Their stability under physiologically-relevant conditions (PBS solution) and n-octanol/PBS distribution coefficient (D7.4) have also been evaluated. Gold(iii) glycoconjugates showed an antiproliferative effect against ovarian carcinoma A2780 cells, with GI50 values in the low micromolar range. Remarkably, their cell growth inhibitory effect increases upon the addition of a glucose transporter 1 (GLUT1) inhibitor, thus ruling out the involvement of GLUT1 in their transport inside the cell. Additional mechanistic studies have been carried out in A2780 cells, supporting the hypothesis of a facilitated diffusion mechanism (possibly mediated by glucose transporters other than GLUT1), and revealing their capability to act as topoisomerase I and II inhibitors and to disrupt mitochondrial membrane integrity, leading to the generation of ROS, thus resulting in the promotion of oxidative stress and, eventually, cell death.

A [Cr2Ni] coordination polymer: slow relaxation of magnetization in quasi-one-dimensional ferromagnetic chains.

The reaction of [Cr3IIIO(OAc)6(H2O)3]NO3·AcOH with 2-hydroxynaphthaldehyde, 2-amino-isobutyric acid and NiCl2·6H2O in MeOH, under basic and solvothermal conditions, led to the formation of the quasi-1D coordination polymer {[CrIII2NiII(L)4(MeOH)2]}n (where L = the dianion of the Schiff base between 2-hydroxynaphthaldehyde and 2-amino-isobutyric acid), which behaves as a ferromagnetic chain, displaying slow relaxation of magnetization.