Synthesis of 17α-substituted ethynylestradiols: Potential ligands for drug vectors

Yaya, Amadou R.; Touaibia, Mohamed; Massarweh, Gassan; Rochon, Fernande D.; Breau, Livain

doi:10.1016/j.steroids.2010.03.004

Cited by 6 publications

(3 citation statements)

References 61 publications

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“…including their conjugation to potentially site-directing molecules, such as folate, porphyrins, adenine, terpenoids, peptides and many others [6][7][8][9][10][11][12][13][14]. The approach used by our research group and few others is based on their potential site-direction through their conjugation to estrogen analogs and derivatives to target estrogen-dependent tissues such as breast, ovarian and uterus [15][16][17][18][19][20]. In the course of our research program, we have selected three potent derivatives amongst three different series of estradiol-linked platinum(II) complex analogs to cisplatin (E-CDDP) exhibiting favorable in vitro biological activity compared to the corresponding cisplatin against breast cancer cell lines [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, antiproliferative activity and estrogen receptor α affinity of novel estradiol-linked platinum(II) complex analogs to carboplatin and oxaliplatin. Potential vector complexes to target estrogen-dependent tissues

Saha

Descôteaux

Brasseur

et al. 2012

European Journal of Medicinal Chemistry

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In the course of efforts to develop 17β-estradiol-linked to anticancer agents targeting estrogen-dependent tissue, we identified three estradiol-linked platinum(II) complex analogs to cisplatin (E-CDDP) derivatives namely: VP-128 (1), CD-38 (2) and JMP-39 (3) that exhibit potent in vitro and in vivo (for derivative VP-128) activity along with interaction with the estrogen receptor α (ERα). In this study, we prepared and biologically evaluated two novel classes of estradiol-linked platinum(II) complex analogs to carboplatin (E-CarboP, 1a-3a) and oxaliplatin (E-OxaP, 1b-3b). E-CarboP and E-OxaP were designed and based on the estradiol-linker scaffold of E-CDDP derivatives previously identified. Consequently, we assessed the importance of the nature of platinum(II) salt on the antiproliferative activity on MCF-7 and MDA-MB-231 human mammary carcinoma cell lines together with affinity for the ERα by replacing the dichloroplatinum(II) moiety by a cyclobutane-1,1-dicarboxylateplatinum(II) or an oxalateplatinum(II) moiety. Except for compound 3b which is inactive at the concentration tested, the antiproliferative activity of all compounds on both human mammary carcinomas cell lines are in micromolar range and are more active than carboplatin and oxaliplatin alone but less active that their E-CDDP counterparts (1-3). In addition, E-CarboP derivatives 1a-3a show very low affinity for ERα whereas E-OxaPs 1b and 2b show higher affinity for ERα than their parents E-CDDPs (1-2), suggesting that the nature of the platinum(II) salt involved in the vector complexes is extremely important to both retain significant antiproliferative activity and selectivity for the ERα and possibility to target estrogen-dependent tissues. Finally, E-OxaPs 1b and 2b are potentially promising alternatives vector complexes to target estrogen-dependent tissues.

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Section: Introductionmentioning

confidence: 99%

Synthesis, antiproliferative activity and estrogen receptor α affinity of novel estradiol-linked platinum(II) complex analogs to carboplatin and oxaliplatin. Potential vector complexes to target estrogen-dependent tissues

Saha

Descôteaux

Brasseur

et al. 2012

European Journal of Medicinal Chemistry

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“…These drawbacks were avoided with the recent synthesis of the analoguous compound 311 bearing no long chain for attachment of the metallic moiety and existing as one isomer (Scheme 71). 149 Addition of the lithium salt of the protected propargyl alcohol on the protected estrone 9, deprotection of the propargyl alcohol function, and iodination of the resulting alcohol gave the steroid 309 with an overall yield of 67%. Introduction of the malonato group was carried out as previously described (vide supra) to afford, after deprotection of the silyl group (TBAF), compound 310 with 45% yield.…”

Section: Monodentate Link Between Platinum Andmentioning

confidence: 99%

Synthesis of Transition-Metal Steroid Derivatives

Bideau

Dagorne

2013

Chem. Rev.

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“…Up until now steroids have showed potential applications as 5α-reductase inhibitors [13], as modulators of inflammation and immunity [14], as inhibitors of 17α-hydroxylase/C 17,20 -lyase [15], as predictor of tamoxifen response in premenopausal breast cancer [16], as progesterone receptor antagonist [17], as glucocorticoid receptor imaging agents [18], as inhibitors of protein tyrosine phosphatase 1B [19], as reversal agents of multidrug resistance in cancer cells [20], as inhibitors of 17β-hydroxysteroid dehydrogenase [21], and as ligands for drug vectors [22]. Some steroidal compounds were used for photodynamic therapy [23], for cancer chemotherapy [24], and for DNA delivery [25].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of new aromatic esters based on 4,16-pregnadiene-6,20-dione skeleton

2010

Chemistry Central Journal

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A series of new aromatic esters based on 4,16-pregnadiene-6,20-dione skeleton, namely 3β-benzoyloxy-4,16-pregnadiene-6,20-dione and 3β-furoyloxy-4,16-pregnadiene- 6,20-dione, which may be good inhibitors for the 5α-reductase enzyme and show high antiandrogenic activity, were synthesized starting from diosgenin. The structures of the steroids were characterized by elemental analysis, 1H NMR, 13C NMR, IR and mass spectrum. Single crystal X-ray diffraction measurement on one of the new compounds, 3β-(p-methoxybenzoyloxy)-4,16-pregnadiene-6,20-dione revealed that the A, B, C, and D ring adopted half chair, distorted chair, distorted chair, and distorted envelope conformation, respectively. The molecules in the crystal were packed face-to-face at the normal van der Waals distances.

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Synthesis of 17α-substituted ethynylestradiols: Potential ligands for drug vectors

Cited by 6 publications

References 61 publications

Synthesis, antiproliferative activity and estrogen receptor α affinity of novel estradiol-linked platinum(II) complex analogs to carboplatin and oxaliplatin. Potential vector complexes to target estrogen-dependent tissues

Synthesis, antiproliferative activity and estrogen receptor α affinity of novel estradiol-linked platinum(II) complex analogs to carboplatin and oxaliplatin. Potential vector complexes to target estrogen-dependent tissues

Synthesis of Transition-Metal Steroid Derivatives

Synthesis and characterization of new aromatic esters based on 4,16-pregnadiene-6,20-dione skeleton

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