1-(2,6-Dichloro-4-hydroxyphenyl)-2-phenylethanes — New Biological Response Modifiers for the Therapy of Breast Cancer. Synthesis and Evaluation of Estrogenic/Antiestrogenic Properties

Schertl, Sabine; Hartmann, Rolf W.; Batzl‐Hartmann, Christine; Schlemmer, Richard; Spruß, Thilo; Bernhardt, Günther; Gust, Ronald; Schönenberger, Helmut

doi:10.1002/1521-4184(200104)334:4<125::aid-ardp125>3.0.co;2-d

Cited by 11 publications

(2 citation statements)

References 26 publications

(15 reference statements)

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“…3) In preceding publications of this series [8,9] we have shown that the anti-breast cancer activity of meso-1-PtCl2 is caused by its estrogenic potency and that a cDDP-like mode of action does not substantially contribute to the inhibition of the tumor. Studies with 1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethane, the hormonally active pharmacophor of meso-1-PtCl2, which, despite the absence of the cytotoxic PtCl2-group, also inhibits the growth of the murine MXT-M-3,2 breast cancer, confirm the discussed mode of action [15,16] .…”

Section: Experimental Schedulementioning

confidence: 60%

Does [meso-1,2-bis(2,6-dichloro-4-hydroxy-phenyl) ethylenediamine]dichloroplatinum(II) act as an immune response modifier? IV. Inhibition of the proliferation-increasing effect of progressively growing MXT-M-3,2 breast cancer on phagocytes by the title compound

Schlemmer

Spruß

Bernhardt

et al. 2001

Arch. Pharm. Pharm. Med. Chem.

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In female B6D2F1 mice bearing an MXT‐M‐3,2 breast cancer graft the level of the phagocytic cells (e.g. of granulocytes and macrophages in the spleen and of granulocytes and monocytes in the blood) is significantly elevated. The positive correlation between the number of the phagocytic cells and the weight of the tumor indicates that the MXT‐M‐3,2 breast cancer promotes myelopoiesis, presumably by secretion of hematopoietic growth factors like GM‐CSF. This process can be described for each phagocyte type by a regression equation. Due to its hormonal potency [meso‐1,2‐bis(2,6‐dichloro‐ 4‐hydroxyphenyl)ethylenediamine]dichloroplatinum(II) (meso‐1‐PtCl2) can reduce the excessive numbers of the granulocytes and macrophages, which seem to be responsible for the progressive growth of the MXT‐M‐3,2 breast cancer. This process leads to an interruption of the vicious circle of mutual growth stimulation of breast cancer cells and these phagocytes. The target of meso‐1‐PtCl2 is the estrogen receptor (ER) of the breast cancer cell. The interaction between meso‐1‐PtCl2 and the ER presumably results in a diminished secretion of hematopoietic growth factors and hence in a decline of the number of phagocytic cells. Meso‐1‐PtCl2 does not inhibit the proliferation of tumor cells by direct interaction with their DNA, as is described for platinum complexes like cDDP. In its mode of action the equipotent, breast cancer inhibiting drug cDDP differs from meso‐1‐PtCl2. This is obvious from the fact that in cDDP‐ but not in meso‐1‐PtCl2‐treated, tumor bearing mice the number of granulocytes and macrophages does not markedly deviate from that in untreated control mice with tumors of the same weight. The drug cDDP probably does not interfere with the mechanism of the secretion of hematopoietic growth factors. The reduction of the number of tumor cells by cDDP leads to a decline of the number of phagocytic cells in accordance with the respective regression equations. In contrast to meso‐1‐PtCl2 and cDDP, ovariectomy causes elevated phagocyte numbers, probably due to the strongly reduced estrogen level. The studies described in this publication indicate that the anti‐breast cancer activity of meso‐1‐PtCl2 is caused by a decimation of phagocytes and with this by an abolition of the tumor promoting effect. Furthermore, a restoration of the natural immunosurveillance seems to be of importance.

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Section: Experimental Schedulementioning

confidence: 60%

Does [meso-1,2-bis(2,6-dichloro-4-hydroxy-phenyl) ethylenediamine]dichloroplatinum(II) act as an immune response modifier? IV. Inhibition of the proliferation-increasing effect of progressively growing MXT-M-3,2 breast cancer on phagocytes by the title compound

Schlemmer

Spruß

Bernhardt

et al. 2001

Arch. Pharm. Pharm. Med. Chem.

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“…69 Interestingly, the ligand meso-1 and its analogues without a steroidal scaffold showed that they have hormone-like effects (estrogenic/antiestrogenic properties) as well as affinity for the ER and inhibit the growth of ER+ breast cancer without cytotoxic effects. 70 On the basis of that, a series of novel platinum(II) complexes with different ligands were synthesized and tested for cytotoxicity against ER+ breast cancer cells. Among them, only complexes 97 and 98 (Figure 12) with at least one NH 2 fragment exhibited strong cytotoxic effects, demonstrating that an NH 2 fragment is a prerequisite for antitumor activity.…”

Section: Platinum Complexesmentioning

confidence: 99%

Research Progress on Bioactive Metal Complexes against ER-Positive Advanced Breast Cancer

et al. 2023

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Breast cancer is the most prevalent cancer in women and represents a serious disease that is harmful to life and health. In 1977, with the approval of tamoxifen, endocrine therapy has become the main clinical treatment for ER-positive (ER+) breast cancer. Although patients initially respond well to endocrine therapies, drug resistance often emerges and side effects can be challenging. To overcome drug resistance, the exploration for new drugs is a priority. Metal complexes have demonstrated significant antitumor activities, and platinum complexes are widely used in the clinic against various cancers, including breast cancer. In this Perspective, the first section describes the classification and mechanism of endocrine therapy drugs for ER+ breast cancer, and the second section summarizes research since 2000 into metal complexes with activity toward ER+ breast cancer. Finally, we discuss the opportunities, challenges, and future directions for metal complexes in the treatment of ER+ breast cancer.

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The McMurry Coupling and Related Reactions

Takeda

Tsubouchi

2013

Organic Reactions

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The McMurry coupling reaction has been recognized as one of the most efficient methods for the synthesis of alkenes from carbonyl compounds. This reaction can be applied to the preparation of various alkenes that are otherwise difficult to prepare. For example, sterically congested tetrasubstituted alkenes as well as medium to large membered rings involving natural products may be accessed via this process. This coupling utilizes various low‐valent titanium reagents generated by the reduction of titanium (III or IV) chloride with K, Zn, LiAlH 4 , C 8 K, amongst others. Furthermore, a variety of low‐valent metal species other than titanium, including aluminum, zirconium, niobium, molybdenum, indium, tungsten, and samarium, have also been found to promote the reductive coupling of carbonyl compounds. The scope and limitations of these reagent systems are reviewed in this chapter, together with the stereochemistry and reaction mechanism. This reaction is categorized into four coupling modes: i) homocoupling giving symmetrical alkenes, ii) mixed coupling giving unsymmetrical alkenes, iii) intramolecular coupling giving cycloalkenes, and iv) tandem coupling giving cyclic polyenes. Characteristics of these reaction modes are described briefly. A selection of synthetic applications are reviewed, including examples of the preparation of sterically congested and strained alkenes, medium to large‐ring compounds, biologically active targets, as well as substrates applicable in material science. Experimental conditions used for this versatile process are summarized to assist the choice of suitable conditions.

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1-(2,6-Dichloro-4-hydroxyphenyl)-2-phenylethanes — New Biological Response Modifiers for the Therapy of Breast Cancer. Synthesis and Evaluation of Estrogenic/Antiestrogenic Properties

Cited by 11 publications

References 26 publications

Does [meso-1,2-bis(2,6-dichloro-4-hydroxy-phenyl) ethylenediamine]dichloroplatinum(II) act as an immune response modifier? IV. Inhibition of the proliferation-increasing effect of progressively growing MXT-M-3,2 breast cancer on phagocytes by the title compound

Does [meso-1,2-bis(2,6-dichloro-4-hydroxy-phenyl) ethylenediamine]dichloroplatinum(II) act as an immune response modifier? IV. Inhibition of the proliferation-increasing effect of progressively growing MXT-M-3,2 breast cancer on phagocytes by the title compound

Research Progress on Bioactive Metal Complexes against ER-Positive Advanced Breast Cancer

The McMurry Coupling and Related Reactions

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