Design, synthesis and biological evaluation of estradiol-PEG-linked platinum(II) hybrid molecules: Comparative molecular modeling study of three distinct families of hybrids

Provencher-Mandeville, Josée; Debnath, Chhanda; Mandal, Saptarshi; Leblanc, Valérie; Parent, Stefan; Asselin, Éric; Bérubé, Gervais

doi:10.1016/j.steroids.2010.09.004

Cited by 36 publications

(25 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cisplatin, carboplatin and oxaliplatin were linked to the estradiol framework at position 16 ( or  of the steroid nucleus. The starting E-CDDP derivatives 1, 2 and 3 material were obtained from estrone with overall yields of 21%, 28% and 22%, respectively using procedures described previously [16][17][18][19]. The different platinum complexes were linked to estrone using either an eleven (derivative 1) or a ten carbon atom alkyl chain (derivative 2) or a triethylene glycol chain (derivative 3).…”

Section: Chemistrymentioning

confidence: 99%

“…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%

“…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]. These derivatives selected are namely: [16][17][18][19]. E-CDDP derivatives 1, 2 and 3 showed better in vitro activity than cisplatin against breast cancer cell lines along with higher affinity with the estrogen…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Chemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…Finally, L-and D-2-pyridylalanine, L-and D-methionine, L-histidine and L-4thiazolylalanine amino acids were selected because they easily form platinum(II) complexes and that they are inexpensive templates to optimize our synthetic approaches [31,32]. We also observed in our recent studies on estrogen combi-molecules that amino pyridine group easily form platinum(II) complexes and show interesting biological activities [33][34][35][36].…”

Section: Design and Chemistrymentioning

confidence: 99%

New platinum(II) complexes conjugated at position 7α of 17β-acetyl-testosterone as new combi-molecules against prostate cancer: Design, synthesis, structure–activity relationships and biological evaluation

Fortin

Brasseur

Morin

et al. 2013

European Journal of Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

Prostate cancer is a major public health problem worldwide and, more specifically, new treatments for hormone-refractory cancers are highly sought by several research groups. Although platinum(II)-based chemotherapy and other strategies grow in interest to treat castration-resistant prostate cancer (CRPC), they still exhibit modest activity on CRPC and overall patient survival. In this study, we designed and prepared new combi-molecules using 17β-acetyl-testosterone and amino acid platinum(II) complexes linked at the position 7α to target and to improve the antiproliferative activity of platinum(II)-based chemotherapy on prostate cancer cells. Twelve chemical intermediates and six new combi-molecules were prepared and characterized. Structure-activity relationships studies show that the platinum complex moiety is essential for an optimal cytocidal activity. Moreover, stereochemistry of the amino acid involved in the platinum complexes had only minor effects on the antiproliferative activity whereas pyridinyl (10a and b) and thiazolyl (10f) complexes exhibited the highest cytocidal activities that are significantly superior to that of cisplatin used as control on human prostate adenocarcinoma LNCaP (AR+), PC3 (AR-) and DU145 (AR-). Compounds 10a, b and f arrested the cell cycle progression in S-phase and induced double strand breaks as confirmed by the phosphorylation of histone H2AX into γH2AX. Compounds 10a and f showed 33 and 30% inhibition, respectively of the growth of HT-1080 tumors grafted onto chick chorioallantoic membranes. Finally, compounds 10a and 10f exhibited low toxicity on the chick embryos (18 and 21% of death, respectively), indicating that these new combi-molecules might be a promising new class of anticancer agents for prostate cancer.

show abstract

“…The anticancer activity of the platinum-based complex, cisplatin (Figure 1), was discovered in the 1960s and has since been used extensively for the treatment of various cancers including ovarian, testicular, lung and breast cancer [1,2,3]. This activity, however, is moderated by dose-limiting side-effects (nephro-, neuro- and ototoxicity) and development of resistance (acquired or intrinsic) [4].…”

Section: Introductionmentioning

confidence: 99%

Transition Metal Intercalators as Anticancer Agents—Recent Advances

Deo

Pages

Ang

et al. 2016

IJMS

View full text Add to dashboard Cite

The diverse anticancer utility of cisplatin has stimulated significant interest in the development of additional platinum-based therapies, resulting in several analogues receiving clinical approval worldwide. However, due to structural and mechanistic similarities, the effectiveness of platinum-based therapies is countered by severe side-effects, narrow spectrum of activity and the development of resistance. Nonetheless, metal complexes offer unique characteristics and exceptional versatility, with the ability to alter their pharmacology through facile modifications of geometry and coordination number. This has prompted the search for metal-based complexes with distinctly different structural motifs and non-covalent modes of binding with a primary aim of circumventing current clinical limitations. This review discusses recent advances in platinum and other transition metal-based complexes with mechanisms of action involving intercalation. This mode of DNA binding is distinct from cisplatin and its derivatives. The metals focused on in this review include Pt, Ru and Cu along with examples of Au, Ni, Zn and Fe complexes; these complexes are capable of DNA intercalation and are highly biologically active.

show abstract

Design, synthesis and biological evaluation of estradiol-PEG-linked platinum(II) hybrid molecules: Comparative molecular modeling study of three distinct families of hybrids

Cited by 36 publications

References 29 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

New platinum(II) complexes conjugated at position 7α of 17β-acetyl-testosterone as new combi-molecules against prostate cancer: Design, synthesis, structure–activity relationships and biological evaluation

Transition Metal Intercalators as Anticancer Agents—Recent Advances

Contact Info

Product

Resources

About