Antitumor steroids. 3. Synthesis and biological activity of 11β-hydroxyestra-1,3,5(10)-triene derivatives with bis-(2-chloroethyl)amino-containing substituents in the 3-position

Abstract

A series of antitumor compounds combining cytotoxic and estrogen action have been synthesized on the basis of 11b-acyloxyestra-1,3,5(10)-trienes. The corresponding synthons, 11b-hydroxy derivatives of estrone, estradiol, and ethynylestradiol, were obtained by oxidative nitration of 3-mono-and 3,17-diesters of these estrogens with ceric ammonium nitrate into the corresponding 9a-hydroxy-and 11b-nitroxy analogs with subsequent hydrogenolysis of the 9-hydroxy groups and removal of the nitrate protecting groups. 111 0091-150X/08/4203-0111

Novel Indoline Spiropyrans Based on Human Hormones β-Estradiol and Estrone: Synthesis, Structure, Chromogenic and Cytotoxic Properties

“…The structure of the obtained compounds was confirmed by 1 H and 13 C NMR, IR, and HRMS. In the IR spectra of compounds (3)(4)(5)(6), characteristic absorption bands of the main structural fragments are observed.…”

“…Many estrogen derivatives possess anticancer activity against various types of cancer cells [9][10][11][12][13]. Estradiol and its metabolites demonstrate an antiproliferative effect comparable to tamoxifen against both estrogen-dependent and estrogen-independent cancer cell lines, including breast tumor cells MCF-7 and MDA-MB 231 [14].…”

Steroid Conjugates as Potential Anti-Cancer Agents

“…Структуры наиболее распространенных производных бис (2-хлорэтил) структурно-родственными конъюгатами, лишенными 7-кетогруппы 12 [50,51]. Эстрансодержащие конъюгаты 16 и 17 были активны против РМЖ и аденокарциномы Сa-755, но 11α-ацетокси-изомер 16 проявлял антиэстрогенную активность, а соответствующий 11β-изомер 17 -значительную эстрогенную активность [52][53][54]. В работах А. Gupta и соавт.…”

Man-Made Cytotoxic Steroids: Exemplary Agents for Cancer Therapy

“…Compounds 34 and 35 showed high antitumor activity despite the presence of 11β-moiety, which acts as an estrogenic pharmacophore, the cytotoxic fragment probably contributing toward the cytostatic effect. 114 Compound 36 with free hydroxyl groups at C 3 and C 17 positions and an alkylating moiety substituted at position C 11 of 11α-hydroxyestra-1,3,5(10)-triene exhibited antitumor activity with total growth inhibition of 92% against mice bearing CA-755 breast adenocarcinoma and B-16 melanoma and also possessed antiestrogen properties. Overall the compounds with the alkylating group attached to C 3 of steroid are more active, H-thymidine to DNA by 71%.…”

“…In contrast to 11α-derivatives, 11β-analogues possessing nitrogen mustard moiety strongly inhibited tumor growth of Ca-755 breast adenocarcinoma but exhibited pronounced estrogenic properties. Compounds 34 and 35 showed high antitumor activity despite the presence of 11β-moiety, which acts as an estrogenic pharmacophore, the cytotoxic fragment probably contributing toward the cytostatic effect …”