Development of ruthenium-based complexes as anticancer agents: toward a rational design of alternative receptor targets

Abstract

<jats:title>Abstract</jats:title><jats:p>In the search for novel anticancer agents, the development of metal-based complexes that could serve as alternatives to cisplatin and its derivatives has received considerable attention in recent years. This becomes necessary because, at present, cisplatin and its derivatives are the only coordination complexes being used as anticancer agents in spite of inherent serious side effects and their limitation against metastasized platinum-resistant cancer cells. Although many metal ions have been considered as possible alternatives to cisplatin, the most promising are ruthenium (Ru) complexes and two Ru compounds, KP1019 and NAMI-A, which are currently in phase II clinical trials. The major obstacle against the rational design of these compounds is the fact that their mode of action in relation to their therapeutic activities and selectivity is not fully understood. There is an urgent need to develop novel metal-based anticancer agents, especially Ru-based compounds, with known mechanism of actions, probable targets, and pharmacodynamic activity. In this paper, we review the current efforts in developing metal-based anticancer agents based on promising Ru complexes and the development of compounds targeting receptors and then examine the future prospects.</jats:p>

Structural Determination of Ruthenium Complexes Containing Bi-Dentate Pyrrole-Ketone Ligands

“…Among of these ruthenium compounds, [(η 6 -cymene)RuCl 2 ] 2 [ 19 ] and RuHCl(CO)(PPh 3 ) 3 [ 20 ] are two important starting materials for synthesizing corresponding ruthenium compounds due to their versatile applications [ 21 , 22 , 23 , 24 ]. Pyrrole represents an important heterocyclic compound for forming materials such as hemes and porphyrinc [ 25 , 26 ], ion-receptors [ 27 , 28 ], bio-active products [ 29 , 30 , 31 ], and light-harvesting pigments [ 32 ], etc.…”

Ruthenium(II) Complexes as Potential Apoptosis Inducers in Cancer Therapy

“…Afterwards, characterization of the anticancer activity and toxicity in vivo of compounds that showed promising results in vitro, is fundamental to their further development (64). A number of in vivo studies have discovered that Ru(II) complexes exhibited anti-cancer activities comparable to, or even better than cisplatin, but with significantly less toxicity and side effects than cisplatin (65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76). Weiss et al synthesized ruthenium complex, [Ru(h 6 -pcymene)Cl 2 (pta)], where pta = 1,3,5-triaza-7-phosphaadaman tane (RAPTA-C).…”

Sulfur-center Reactivity toward Oxygenation Mediated by Ruthenium: Effective Bioactive Compounds (A Review)

“…[86][87][88] Recent research on the coordination polymers of Ru II -organosulfur compounds having benzoate group combine with sulfinate functions; their synthesis utilising RuCl 3 •3H 2 O and dtdb [2,2′-dithiodibenzoic acid], and arrangements of atoms and groups inside the polymer and chemical behaviour were described. 89 Such ruthenium sulfur compounds and their derivatives being the member of heavier platinum group metals, are found to be active component to show the in vitro cytotoxicity [90][91][92] and can become active precursor for the anticancer drug design [93][94][95] in the field of biological applications because of these components are lesser toxic for remaining healthy part of the body. 96…”