14913-33-8Relevant articles and documents
Conversion of Acetonitrile into Acetamide in the Co-ordination Spheres of cis- and trans-M(II)(amine)2 (M = Pt or Pd). Solution and Crystal Structural Studies
Erxleben, Andrea,Mutikainen, Ilpo,Lippert, Bernhard
, p. 3667 - 3676 (1994)
The preparation and solution behaviour of mono- and bis-acetonitrile complexes of cis, (en = ethane-1,2-diamine) and trans- has been investigated.The nitrile complexes are hydrolysed to acetamidate, acetamidate-bridged and mixed acetamidate-acetonitrile species.It is shown that an essential feature of monomeric acetamidate complexes with cis configuration is their tendency to dimerize to dinuclear platinum compounds having bridging amidate ligands.The resulting dimers undergo a facile head-to-tail to head-to-head rearrangement without any detectable intermediate.Solution studies of the mononitrile complex trans-(1+) at around neutral pH reveal the formation of trans-(1+), suggesting a preceding ligand exchange.The reactions of platinum with MeCN are compared with those of the kinetically labile palladium.The nitrile complex cis-ClO4 and the mixed-ligand complex trans-ClO4 were characterized by X-ray crystallography: cis-ClO4, monoclinic, space group P21/c, a = 10.618(10), b = 10.625(8), c = 9.176(7) Angstroem, β = 111.20(6) deg, Z = 4; trans-ClO4, monoclinic, space group P21/c, a = 8.601(6), b = 19.508(19), c = 7.625(4) Angstroem, β = 115.29(5) deg, Z = 4.
Characterization of the mechanism of reduction of trans-diamminetetrachloroplatinum(IV) by l-cysteine and dl-homocysteine
Lu, Taotao,Dong, Jingran,Nan, Chunxia,Huo, Shuying,Shen, Shigang,Sun, Sufang,Shi, Tiesheng
, p. 869 - 875 (2015)
The interactions between Pt(IV) anticancer prodrugs incorporating two ammines/amines in trans positions in their equatorial planes and some important thiols have not been exploited to date. In this work, the reduction of one such Pt(IV) prodrug, namely trans-[Pt(NH3)2Cl4], by two thiol-containing amino acids l-cysteine (Cys) and dl-homocysteine (Hcy) which are prevalent in human plasma has been characterized by stopped-flow spectroscopic and ESI high-resolution mass spectral methods. The reduction process obeys overall second-order kinetics. The dependencies of the observed second-order rate constants k′ on pH have been established between pH 4.03 and 11.24. Mass spectral analysis indicates that cystine and homocystine are the dominant products for the Cys and Hcy oxidations, respectively. The suggested reaction mechanism involves all possible protolytic species of Cys/Hcy, which attack one of the two apically coordinated chlorides in parallel (all as rate-determining steps), leading to a Cl+ transfer to the attacking sulfur atom. The rate expression has been derived, and the rate constants for the rate-determining steps have been calculated. Features of the reduction process are discussed based on the obtained rate constants. The overall kinetic and mechanistic picture enables an in-depth understanding of the reduction process of this type of Pt(IV) anticancer prodrug.
A Pt(IV)-based mononitro-naphthalimide conjugate with minimized side-effects targeting DNA damage response via a dual-DNA-damage approach to overcome cisplatin resistance
Li, Linrong,Li, Yingguang,Liu, Hanfang,Ma, Jing,Niu, Jie,Xie, Songqiang,Yue, Kexin
, (2020)
Platinum(Pt)(II) drugs and new Pt(IV) agents behave the dysregulation of apoptosis as the result of DNA damage repair and thus, are less effective in the treatment of resistant tumors. Herein, mononitro-naphthalimide Pt(IV) complex 10b with minimized side-effects was reported targeting DNA damage response via a dual-DNA-damage approach to overcome cisplatin resistance. 10b displayed remarkably evaluated antitumor (70.10percent) activities in vivo compared to that of cisplatin (52.88percent). The highest fold increase (FI) (5.08) for A549cisR cells and the lowest (0.72) for A549 indicated 10b preferentially accumulated in resistant cell lines. The possible molecular mechanism indicates that 10b targets resistant cells in a totally different way from the existing Pt drugs. The cell accumulation and the Pt levels in genomic DNA from 10b is almost 5 folds higher than that of cisplatin and oxaliplatin, indicating the naphthalimide moiety in 10b exhibits preferentially DNA damage. Using 5′-dGMP as a DNA model, the DNA-binding properties of 10b (1 mM) with 5′-dGMP (3 mM) in the presence of ascorbic acid (5 mM) deduced that 10b was generated by the combination of cisplatin with 5′-dGMP after reduction by ascorbic acid. Moreover, 10b promoted the expression of p53 gene and protein more effectively than cisplatin, leading to the increased anticancer activity. The up-regulated γH2A.X and down-regulated RAD51 indicates that 10b not only induced severe DNA damage but also inhibited the DNA damage repair, thus resulting in its higher cytotoxicity in comparison to that of cisplatin. Their preferential accumulation in cancer cells (SMMC-7721) compared to the matched normal cells (HL-7702 cells) demonstrated that they were potentially safe for clinical therapeutic use. In addition, the higher therapeutic indices of 10b for 4T1 cells in vivo indicated that naphthalimide-Pt(IV) conjugates behaved a vital function in the treatment of breast cancer. For the first time, our study implies a significant strategy for Pt drugs to treat resistance cancer targeting DNA damage repair via dual DNA damage mechanism in a totally new field.
A Keggin-type polyoxotungstate-coordinated diplatinum(II) complex: Synthesis, characterization, and stability of the cis-platinum(II) moieties in dimethylsulfoxide and water
Kato, Masao,Kato, Chika Nozaki
, p. 982 - 985 (2011)
The synthesis of a Keggin-type polyoxotungstate-coordinated diplatinum(II) complex, [(CH3)4N]3[α-PW 11O39{cis-Pt(NH3)2}2], obtained by reaction of Keggin-type mono-lacunary polyoxotungstate, [α-PW11O39]7-, with cis- diamminedichloroplatinum(II) in an aqueous solution is described. The complex was characterized by elemental analysis, thermogravimetric/differential thermal analysis (TG/DTA), Fourier transform infrared (FTIR), ultraviolet-visible (UV-vis), and solution 1H, 31P, and 183W nuclear magnetic resonance (NMR) spectroscopy. The two cis-platinum(II) moieties, [cis-Pt(NH3)2]2+, were coordinated each to two oxygen atoms in a mono-vacant site of [α-PW11O 39]7- with Cs symmetry, and the cis-conformation was highly stable in dimethylsulfoxide and water.
Coordination-drIVen self-assembly of a Pt(IV) prodrug-conjugated supramolecular hexagon
Yue, Zhizhou,Wang, Han,Li, Yiming,Qin, Yi,Xu, Lin,Bowers, David J.,Gangoda, Mahinda,Li, Xiaopeng,Yang, Hai-Bo,Zheng, Yao-Rong
, p. 731 - 734 (2018)
This article presents a new strategy to engage coordination-driven self-assembly for platinum drug delivery. The self-assembled supramolecular hexagon is conjugated with three equivalents of Pt(iv) prodrugs and displays a superior therapeutic index compared to cisplatin against a panel of human cancer cell lines.
The effect of geometric isomerism on the anticancer activity of the monofunctional platinum complex: Trans -[Pt(NH3)2(phenanthridine)Cl]NO3
Zhou, Wen,Almeqdadi, Mohammad,Xifaras, Michael E.,Riddell, Imogen A.,Yilmaz, ?mer H.,Lippard, Stephen J.
, p. 2788 - 2791 (2018)
A trans-DDP based monofunctional phenanthridine Pt(ii) complex was synthesized and characterized. Its anticancer activity was studied in vitro on a panel of human cancer cell lines and mouse intestinal cancer organoids. This complex displays significant antitumor properties, with a different spectrum of activity than that of classic bifunctional cross-linking agents like cisplatin.
trans-Platinum(iv) pro-drugs that exhibit unusual resistance to reduction by endogenous reductants and blood serum but are rapidly activated inside cells:1H NMR and XANES spectroscopy study
Chen, Catherine K. J.,Gibson, Dan,Hambley, Trevor W.,Kappen, Peter
supporting information, p. 7722 - 7736 (2020/06/26)
Recent results have confirmed that protection of transplatin from reactions on the path to cancer cells substantially increases their activity, suggesting that such complexes have greater potential than previously thought. In this study we have investigated the use of the platinum(iv) oxidation state and the tetracarboxylate coordination sphere to determine whether these features could impart the same stability totrans-diammineplatinum complexes that they do tocis-diam(m)ineplatinum complexes. Theciscomplexes exhibit resistance to reduction byl-ascorbate and human blood serum, but are readily reduced inside cancer cells. Studies of reduction monitored by1H NMR revealed that oxidation oftrans-diammineplatinum(ii) complexes does not always result in significant stabilisation, but the complexestrans, trans, trans-[Pt(OAc)4(NH3)2] (OAc = acetate) andtrans, trans, trans-[Pt(OPr)2(OAc)2(NH3)2] (OPr = propionate) exhibit second order half-lives of 33 h and 5.9 days respectively in the presence of a ten-fold excess ofl-ascorbate. XANES spectroscopy studies of reduction in blood models showed thattrans, trans, trans-[Pt(OAc)4(NH3)2] is stable in blood serum for at least 24 hours, but is reduced rapidly in whole blood and was observed to have a half-life of approximately 4 hours in DLD-1 colon cancer cells. Consequently, the tetracarboxylatoplatinum(iv) moiety has the properties required to enable the delivery oftrans-diammine platinum complexes to cancer cells.
Development of an Efficient Dual-Action GST-Inhibiting Anticancer Platinum(IV) Prodrug
Lee, Keefe Guang Zhi,Babak, Maria V.,Weiss, Andrea,Dyson, Paul J.,Nowak-Sliwinska, Patrycja,Montagner, Diego,Ang, Wee Han
, p. 1210 - 1217 (2018/06/04)
The cytotoxicity of cisplatin (cDDP) is enhanced when co-administered with ethacrynic acid (EA), a glutathione S-transferase (GST) inhibitor. A PtIV–EA conjugate containing a cDDP core and two axial ethacrynate ligands (compound 1) was shown to be an excellent inhibitor of GST, but did not readily release a PtII species to exert a synergistic cytotoxic effect. In this study, a redesigned PtIV construct composed of a cDDP core with one axial ethacrynate ligand and one axial hydroxido ligand (compound 2) was prepared and shown to overcome the limitations of compound 1. The EA ligand in 2 is readily released in vitro together with a cytotoxic PtII species derived from cisplatin, working together to inhibit cell proliferation in cDDP-resistant human ovarian cancer cells. The in vitro activity translates well in vivo with 2, showing effective (～80 %) inhibition of tumor growth in a human ovarian carcinoma A2780 tumor model, while showing considerably lower toxicity than cisplatin, thus validating the new design strategy.
