Recent advances in ruthenium and platinum based supramolecular coordination complexes for antitumor therapy.

Since the discovery of cisplatin for antitumor activity, the platinum (Pt) based antitumor drugs have received significant attention and launched a new era to explore the transition metal complexes for therapy. However, these small Pt-based antitumor drugs have some limitations for their clinic application, such as short blood circulation time and limited accumulation at tumor site, which was mainly due to their poor water solubility and small molecule size. To overcome these obstacles, developing new generation of transition-metal based complexes as anticancer agents is urgently needed. For the unique properties, the ruthenium (Ru) based complexes have attractive significant attention and be expected to be a substitute for Pt-based anticancer agents. Due to the nanometer size, unique geometry, relatively high surface charge and unique photophysical properties, the transition-metal based supramolecular coordination complexes (SCCs) which exhibited excellent antitumor efficiency and possessed desirable bioapplications such as drug loading, bioimaging and biosensing have attracted great attention as anticancer agents. In this minireview, we will highlight the recent development of ruthenium (Ru) and Platinum (Pt) based SCCs as potential anticancer agents.

Zhang X ，Liu D ，Lv F ，Yu B ，Shen Y ，Cong H ... -  《-》

A Cancer Cell-Selective and Low-Toxic Bifunctional Heterodinuclear Pt(IV)-Ru(II) Anticancer Prodrug.

Ma L ，Lin X ，Li C ，Xu Z ，Chan CY ，Tse MK ，Shi P ，Zhu G ... -  《-》

Ruthenium Complexes as Anticancer Agents: A Brief History and Perspectives.

Platinum (Pt)-based anticancer drugs such as cisplatin have been used to treat various cancers. However, they have some limitations including poor selectivity and toxicity towards normal cells and increasing chemoresistance. Therefore, there is a need for novel metallo-anticancers, which has not been met for decades. Since the initial introduction of ruthenium (Ru) polypyridyl complex, a number of attempts at structural evolution have been conducted to improve efficacy. Among them, half-sandwich Ru-arene complexes have been the most prominent as an anticancer platform. Such complexes have clearly shown superior anticancer profiles such as increased selectivity toward cancer cells and ameliorating toxicity against normal cells compared to existing Pt-based anticancers. Currently, several Ru complexes are under human clinical trials. For improvement in selectivity and toxicity associated with chemotherapy, Ru complexes as photodynamic therapy (PDT), and photoactivated chemotherapy (PACT), which can selectively activate prodrug moieties in a specific region, have also been investigated. With all these studies on these interesting entities, new metallo-anticancer drugs to at least partially replace existing Pt-based anticancers are anticipated. This review covers a brief description of Ru-based anticancer complexes and perspectives.

Lee SY ，Kim CY ，Nam TG 《Drug Design Development and Therapy》

Heterodinuclear Pt(iv)-Ru(ii) anticancer prodrugs to combat both drug resistance and tumor metastasis.

Ma L ，Ma R ，Wang Z ，Yiu SM ，Zhu G ... -  《-》

Synthesis, Spectroscopic Properties, Crystal Structure And Biological Evaluation of New Platinum Complexes with 5-methyl-5-(2-thiomethyl)ethyl Hydantoin.

The accidental discovery of Cisplatin's growth-inhibiting properties a few decades ago led to the resurgence of interest in metal-based chemotherapeutics. A number of well-discussed factors such as severe systemic toxicity and unfavourable physicochemical properties further limit the clinical application of the platinating agents. Great efforts have been undertaken in the development of alternative platinum derivatives with an extended antitumor spectrum and amended toxicity profile as compared to the reference drug cisplatin. The rational design of conventional platinum analogues and the re-evaluation of the empirically derived "structure- activity" relationships allowed for the synthesis of platinum complexes with great diversity in structural characteristics, biochemical stability and antitumor properties. The new compounds have been studied by elemental analyses, IR, NMR and mass spectral analyses. The structures of the organic compound and one of the new mixed/ammine Pt(II) complexes were studied by X-ray diffraction analysis. The cytotoxic effects of the compounds were studied vs. the referent antineoplastic agent cisplatin against four human tumour cell lines using the standard MTT-dye reduction assay for cell viability. The most promising complex 3 was investigated for acute toxicity in male and female H-albino-mice models. A new organic compound (5-methyl-5-(2-thiomethyl)ethyl hydantoin) L bearing both S- and Ncoordinating sites and three novel platinum complexes, 1, 2 and 3 were synthesized and studied. Spectral and structural characterization concluded monodentate S-driven coordination of the ligand L to the metal center in complexes 1 and 2, whereas the same was acted as a bidentate N,S-chelator in complex 3. Ligand L crystallizes in the tetragonal space group I41/a (No 88) with one molecule per asymmetric unit. While complex 3 crystallizes in the monoclinic space group P21/c (No 14) with one molecule per asymmetric unit. In the same complex 3, the platinum ion coordinates an L ligand, a chloride ion and an ammonia molecule. In the in vitro experiments, the tested L and complexes 1 and 2 exhibited negligible cytotoxic activity in all tumor models. Accordingly, complex 3 is twice as potent as cisplatin in the HT-29 cells and is at least as active as cisplatin on the MDA-MB-231 breast cancer cell line. In the in vivo toxicity estimation of complex 3 no signs of common toxicity were observed. The Pt(II)-bidentate complex 3 exhibited significant cytotoxic potential equaling or surpassing that of the reference drug cisplatin in all the tested tumor models. Negligible anticancer activity on the screened tumor types has been shown by the ligand L and its Pt(II) and Pt(IV) complexes 1 and 2, respectively. Our study on the acute toxicity of the most active complex 3 proved it to be non-toxic in mice models.

Bakalova AG ，Buyukliev RT ，Nikolova RP ，Shivachev BL ，Mihaylova RA ，Konstantinov SM ... -  《-》