Metal complexes with biologically important ligands. 62. Platinum(II) complexes of 3-(2-aminoethoxy)estrone and -estradiol

Altman, J.; Castrillo, Thaı́s; Beck, Wolfgang; Bernhardt, Güenther; Schoenenberger, H.

doi:10.1021/ic00021a022

Cited by 31 publications

(16 citation statements)

References 2 publications

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“…These agents exhibit cytotoxic effects in mammary carcinoma and prostate cancer cell lines whereas lack activity in the hormone-independent cell line MDA-MB 231 [107]. The first attempts to append cytotoxic platinum moieties to estrogen core structure have employed coupling of the linking groups to the hydroxyl functions at the 3-rd or the 17β positions in estradiol [108][109][110]. Both of these hydroxyls however are crucial for the binding of the ligand to the estrogen receptor and thus the observed functionalizing with platinum moieties practically compromised the receptor recognition [111].…”

Section: Platinum Complexes With Tumor Tissue-targeted Cytotoxic Actionmentioning

confidence: 99%

Novel Approaches Towards Development of Non-Classical Platinum-Based Antineoplastic Agents: Design of Platinum Complexes Characterized by an Alternative DNA-Binding Pattern and/or Tumor-Targeted Cytotoxicity

Momekov¹,

Bakalova²,

Karaivanova

2005

CMC

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Cisplatin is an essential antineoplastic agent whose introduction in clinical use revolutionized the treatment of several solid malignancies, especially those of germinative origin. The unfavorable toxicological profile of this drug, however as well as the resistance of some common malignancies solicited the search of platinum complexes, characterized by lower toxicity and/or broader antitumor spectrum. Thus during the last three decades a plethora of several thousand platinum coordination compounds have been synthesized and evaluated as potential antineoplastic agents. Despite of the numerous compounds investigated however only few of the proved to be of clinical significance and actually none of them could be considered as an ideal substitute for cisplatin regarding both lower toxicity and broader spectrum of anticancer activity. To a great extent the platinum-based drug discovery was confined at structural modification of the parent compound in line with the classic structure-activity relationship concept. Conversely, since the majority of platinum complexes developed so far are closely related structural analogues of cisplatin, it is not surprising that they produce similar cellular effects and any altered pattern of antitumor activity and/or toxicity is likely to be due to pharmacokinetic, rather than truly mechanistic, factors. Studies over the last few years have shown that the structural resemblance to cisplatin is not an absolute requirement for cytotoxicity, which broadens the search for cisplatin analogues towards non-classical compounds with prominent structural/pharmacodynamic dissimilarity to the prototype. This review covers the major approaches to elaboration of non-classical platinum complexes with emphasis on complexes interacting with DNA in a cisplatin-dissimilar fashion and complexes with tumor-targeted cytotoxicity.

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Section: Platinum Complexes With Tumor Tissue-targeted Cytotoxic Actionmentioning

confidence: 99%

Novel Approaches Towards Development of Non-Classical Platinum-Based Antineoplastic Agents: Design of Platinum Complexes Characterized by an Alternative DNA-Binding Pattern and/or Tumor-Targeted Cytotoxicity

Momekov¹,

Bakalova²,

Karaivanova

2005

CMC

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“…Altman introduced her knowledge on amino functionalized steroids to Beck's group; they transformed such steroids into amides with activated, PtCl 2 -protected amino acids and peptides to give cis-PtCl 2 -complexes like 10a-c [119,120]. The comparative testing of these complexes on ER + MCF-7 and ER − MDA-MB-231 breast cancer cells showed a somewhat stronger sensitivity of the former ER-containing cell line than that of the latter possessing no significant ER levels.…”

Section: Replacement Of the Oh Groups In Positions 3 And/or 17ˇin Thementioning

confidence: 99%

“…Similarly, estrone, testosterone and prednisone were converted with activated cis-Cl 2 Pt(GlyOH) 2 into the corresponding esters 11-13 (Altman et al [120]). Pharmacological data of these compounds are not available.…”

Section: Replacement Of the Oh Groups In Positions 3 And/or 17ˇin Thementioning

confidence: 99%

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Optimization of cisplatin for the treatment of hormone dependent tumoral diseases

Gust

Beck

Jaouen

et al. 2009

Coordination Chemistry Reviews

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“…[39][40][41] Early studies on estrogenic metal complexes focused primarily on cisplatin derivatives linked to estrogens through one of the two steroid hydroxy groups. [38,[42][43][44][45][46][47] These two hydroxy groups are very important in receptor recognition [48] and, probably in consequence, there was little gain from such conjugation. Jaouen [49] explored conjugation of steroids to organometallic carbonyl compounds (for application in carbonylmetalloassays) and demonstrated that organometallics could be attached at the 17a-position of estradiol with retention of some steroid receptor binding ability.…”

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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Metal complexes with biologically important ligands. 62. Platinum(II) complexes of 3-(2-aminoethoxy)estrone and -estradiol

Cited by 31 publications

References 2 publications

Novel Approaches Towards Development of Non-Classical Platinum-Based Antineoplastic Agents: Design of Platinum Complexes Characterized by an Alternative DNA-Binding Pattern and/or Tumor-Targeted Cytotoxicity

Novel Approaches Towards Development of Non-Classical Platinum-Based Antineoplastic Agents: Design of Platinum Complexes Characterized by an Alternative DNA-Binding Pattern and/or Tumor-Targeted Cytotoxicity

Optimization of cisplatin for the treatment of hormone dependent tumoral diseases

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

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