Synthesis of 17β-estradiol-linked platinum(II) complexes and their cytocidal activity on estrogen-dependent and -independent breast tumor cells

Perron, Valérie; Rabouin, Daniel; Asselin, Éric; Parent, Stefan; C.‐Gaudreault, René; Bérubé, Gervais

doi:10.1016/j.bioorg.2004.06.009

Cited by 54 publications

(32 citation statements)

References 23 publications

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“…A unique class of estradiol-Pt(Ⅱ) hybrid complex 24, which binds DNA indirectly through hydrogen bonds, showed good potential in vitro and in vivo for the treatment of hormone dependent cancers [72] , in particular for breast cancer without any apparent side effects [73][74][75][76] . When n was 4, complex 24 was more effective against several types of cancers than cisplatin [77] .…”

Section: Platinum-based Supermolecules As Antitumor Agentsmentioning

confidence: 99%

Review on supermolecules as chemical drugs

Zhou

Gan

Zhang

et al. 2009

Sci. China Ser. B-Chem.

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Supramolecular medicinal chemistry field has been a quite rapidly developing, increasingly active and newly rising interdiscipline which is the new expansion of supramolecular chemistry in pharmaceutical sciences, and is gradually becoming a relatively independent scientific area. Supramolecular drugs could be defined as medicinal supermolecules formed by two or more molecules through noncovalent bonds. So far a lot of supermolecules as chemical drugs have been widely used in clinics. Supermolecules as chemical drugs, i.e. supramolecular chemical drugs or supramolecular drugs, which might have the excellences of lower cost, shorter period, higher potential as clinical drugs for their successful research and development, may possess higher bioavailability, better biocompatibility and drug-targeting, fewer multidrug-resistances, lower toxicity, less adverse effect, and better curative effects as well as safety, and therefore exhibit wide potential application. These overwhelming advantages have drawn enormous special attention. This paper gives the definition of supramolecular drugs, proposes the concept of supramolecular chemical drugs, and systematically reviews the recent advances in the research and development of supermolecules, including organic and inorganic complex ones as chemical drugs in the area of antitumor, anti-inflammatory, analgesic, antimalarial, antibacterial, antifungal, antivirus, anti-epileptic, cardiovascular agents and magnetic resonance imaging agents and so on. The perspectives of the foreseeable future and potential application of supramolecules as chemical drugs are also presented.

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Section: Platinum-based Supermolecules As Antitumor Agentsmentioning

confidence: 99%

Review on supermolecules as chemical drugs

Zhou

Gan

Zhang

et al. 2009

Sci. China Ser. B-Chem.

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“…Following the rationale that for the binding of 17b-estradiol derivatives to the nuclear estrogen receptor ER a a free 3-OH is more important than a free 17-OH group, most Pt II complex conjugates contain the steroid tethered at positions remote from the A-ring such as C16 or C17. [11][12][13] However, there has also been growing evidence for the involvement of sex hormone binding globulins (SHBG) in the development of sex-hormone-dependent tumours. SHBG acts as a carrier for estrogens and androgens and also interacts with plasma membranes of cells in a ligand-dependent manner, thereby stimulating intracellular signalling pathways that alter cell growth and function.…”

Section: Introductionmentioning

confidence: 99%

Steroid Conjugates of Dichloro(6‐aminomethylnicotinate)platinum(II): Effects on DNA, Sex Hormone Binding Globulin, the Estrogen Receptor, and Various Breast Cancer Cell Lines

et al. 2007

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Esters of 6-aminomethylnicotinic acid with various steroidal alcohols were treated with K(2)PtCl(4) to give the N,N-chelated dichloroplatinum(II) complex conjugates 4. Their interaction with plasmid DNA was monitored by electrophoretic mobility measurements. Their affinities towards sex hormone binding globulin (SHBG) and towards the nuclear estrogen receptor ER(alpha) were assessed by competitive displacement radioassays. The inhibitory effect of 4 on breast tumour cells MCF-7 ER(+)/ER(-) and MDA-MB-231 was investigated in vitro. Conjugates with 3-O-linked estrogens 4 a,b or 17-O-linked androgens 4 g bound strongly to SHBG. The conjugate complex 4 b, featuring a 3-O-linked estradiol, also bound strongly and agonistically to the estrogen receptor. It also elicited distinct growth retardation of MCF-7 (ER(+)) cells, presumably by a mechanism different from that of cisplatin.

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“…[51] Osella has more recently described an agent bearing a platinum-malonato unit attached through the 17a-position but which shows negligible receptor binding, [43] while BØrubØ has prepared mixtures of estrogens with dichloroplatinum units attached at the 16a-and 16b-positions which show more promise. [52][53][54] Lippard has demonstrated that steroid hormones can sensitise cancer cells to platinum drugs (through induction of HMG over-expression) [55] and has attempted to harness this affect through design of an estrogenic platinum(iv) agent intended to hydrolyse and reduce, thus forming cisplatin and an estrogen after entering the cell. [56] The purpose of this work was to develop a molecule which combined: i) a steroid binding motif to facilitate cellular delivery to cells with estrogen receptors, and ii) a DNA binding motif designed for interaction with DNA.…”

Section: Introductionmentioning

confidence: 99%

An Estrogen–Platinum Terpyridine Conjugate: DNA and Protein Binding and Cellular Delivery

Hannon

Green

Fisher

et al. 2006

Chemistry A European J

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A platinum metal complex in which terpyridine joins estradiol (via an ethynyl link) to a platinum with a labile ligand (chloride) has been designed, synthesised and its X-ray crystal structure determined. The aim of this work was to link a targeting motif (in this case estrogen) to a metal-based biomolecule recognition unit (the platinum moiety). The target molecule: 17alpha-[4'-ethynyl-2,2':6',2'-terpyridine]-17beta-estradiol platinum(II) chloride (PtEEtpy) has been shown to bind to both human and bovine serum albumin (SA) and to DNA. FTICR mass spectrometry shows that the bimolecular units are in each case linked through coordination to the platinum with displacement of the chloride ligand. Circular dichroism indicates that a termolecular entity involving PtEEtpy, SA and DNA is formed. A range of electrospray mass spectrometry experiments showed that the PtEEtpy complex breaks and forms coordination bonds relatively easily. A whole cell estrogen receptor assay in an estrogen receptor positive cell (MCF-7) confirms binding of both EEtpy and PtEEtpy to the estrogen receptor in cells. The work demonstrates the concept of linking a targeting moiety (in this case estrogen) to a DNA binding agent.

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Synthesis of 17β-estradiol-linked platinum(II) complexes and their cytocidal activity on estrogen-dependent and -independent breast tumor cells

Cited by 54 publications

References 23 publications

Review on supermolecules as chemical drugs

Review on supermolecules as chemical drugs

Steroid Conjugates of Dichloro(6‐aminomethylnicotinate)platinum(II): Effects on DNA, Sex Hormone Binding Globulin, the Estrogen Receptor, and Various Breast Cancer Cell Lines

An Estrogen–Platinum Terpyridine Conjugate: DNA and Protein Binding and Cellular Delivery

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