Ru(II) Compounds: Next-Generation Anticancer Metallotherapeutics?

Abstract

Metal based therapeutics are a precious class of drugs in oncology research that include examples of theranostic drugs, which are active in both diagnostic, specifically imaging, and therapeutics applications. Ruthenium compounds have shown selective bioactivity and the ability to overcome the resistance that platinum-based therapeutics face, making them effective oncotherapeutic competitors in rational drug invention approaches. The development of antineoplastic ruthenium therapeutics is of particular interest because ruthenium containing complexes NAMI-A, KP1019, and KP1339 entered clinical trials and DW1/2 is in preclinical levels. The very robust, conformationally rigid organometallic Ru(II) compound DW1/2 is a protein kinase inhibitor and presents new Ru(II) compound designs as anticancer agents. Over the recent years, numerous strategies have been used to encapsulate Ru(II) derived compounds in a nanomaterial system, improving their targeting and delivery into neoplastic cells. A new photodynamic therapy based Ru(II) therapeutic, TLD-1433, has also entered clinical trials. Ru(II)-based compounds can also be photosensitizers for photodynamic therapy, which has proven to be an effective new, alternative, and noninvasive oncotherapy modality.

Selective Targeting of the Zinc Finger Domain of HIV Nucleocapsid Protein NCp7 with Ruthenium Complexes

“…NAMI‐A (ImH[ trans ‐RuCl 4 (DMSO)(Im)], Im=imidazole), an anticancer drug in clinic trial, was chosen in the reaction. Two arene Ru complexes ( Ru‐1 and Ru‐2 , see Figure ), which have shown high potency to tumor cells, were also used . Two other di‐nuclear Ru complexes ( Ru‐3 and Ru‐4 ) with the bridge of chloro or 1‐{4‐[(1H‐imidazol‐1‐yl)methyl]benzyl}‐1H‐imidazole ( p ‐bib) ligand were used for comparison ,.…”

Anticancer Potential of Diiron Vinyliminium Complexes

“…Instead, extensive degradation of a complex in biological medium could lead to fragments or aggregates that lack a clear pharmacological role . The titanium complexes budotitane and titanocene dichloride failed clinical trials for reasons that are imputable to these drawbacks, whereas the ruthenium(III) complex KP1019 and the platinum(II) complex cis ‐dichlorobis(cyclopentylamine)platinum(II) were limited by their poor water solubility.…”

Recent Considerations in the Application of RAPTA‐C for Cancer Treatment and Perspectives for Its Combination with Immunotherapies

“…[26,[35][36][37][38] Therapeutic candidates that entered clinical evaluation include NAMI-A, [26,39,40] KP1019, [36,41] and its water soluble sodium salt (N)KP1339 [42,43] (Figure 1). [26,[35][36][37][38] Therapeutic candidates that entered clinical evaluation include NAMI-A, [26,39,40] KP1019, [36,41] and its water soluble sodium salt (N)KP1339 [42,43] (Figure 1).…”

“…The continuous occurrence of side effects limits the efficacy of these derivatives, while alternative approaches focus on the development of new compounds based on platinum(IV) [16] or on other metals that also have relevant pharmacological properties. [22][23][24][25] Numerous ruthenium-based compounds are able to overcome resistance pathways as well as exhibiting anti-tumor, antimetastatic, and anti-angiogenic properties, [26] but only three have been studied in clinical trials for the treatment of cancer, namely imidazolium-trans-tetrachloro(dimethylsulfoxide) imidazoleruthenium(III) (NAMI-A), trans-[tetrachlorobis (1Hindazole) ruthenate(III)] (KP1019), and (N)KP1339. [22][23][24][25] Numerous ruthenium-based compounds are able to overcome resistance pathways as well as exhibiting anti-tumor, antimetastatic, and anti-angiogenic properties, [26] but only three have been studied in clinical trials for the treatment of cancer, namely imidazolium-trans-tetrachloro(dimethylsulfoxide) imidazoleruthenium(III) (NAMI-A), trans-[tetrachlorobis (1Hindazole) ruthenate(III)] (KP1019), and (N)KP1339.…”