31750-47-7Relevant articles and documents
Tamoxifen-zinc(II) phthalocyanine conjugates for target-based photodynamic therapy and hormone therapy
Zhang, Feng-Ling,Huang, Ning,Weng, Hui-Lan,Xue, Jin-Ping
, p. 1073 - 1083 (2019)
Although photodynamic therapy has been extensively studied in recent years and preclinical studies have shown promising results, strategies for enhancing PDT outcomes and reducing side effects still urgently need to be developed. In this study, a series of Tamoxifen-zinc(II) phthalocyanine conjugates have been designed and synthesized. In these "double-headed" conjugates, photodynamic therapy agent zinc(II) phthalocyanine and hormone therapy drug Tamoxifen were combined via oligoethylene glycol linkers. The conjugates show high specificity, and some of them show cytotoxic effects against the MCF-7 cells overexpressed Estrogen receptor, due to the targeting and cytostatic Tamoxifen moiety. Upon illumination, all these conjugates show high cytotoxicity due to the photosensitizing phthalocyanine unit. Their structure-activity relationship was also assessed. The results show that α-substituted Tamoxifen-zinc(II) phthalocyanine conjugates are highly promising anticancer targeting agents which exhibit additive effects of photodynamic therapy and hormone therapy.
Unique SERM-like properties of the novel fluorescent tamoxifen derivative FLTX1
Marrero-Alonso, Jorge,Morales, Araceli,García Marrero, Benito,Boto, Alicia,Marín, Raquel,Cury, Débora,Gómez, Tomás,Fernández-Pérez, Leandro,Lahoz, Fernando,Díaz, Mario
, p. 898 - 910 (2013)
Tamoxifen is a selective estrogen receptor modulator extensively used on estrogen receptor-positive breast cancer treatment. However, clinical evidences demonstrate the increased incidence of undesirable side effects during chronic therapies, the most life threatening being uterine cancers. Some of these effects are related to tissue-dependent estrogenic actions of tamoxifen, but the exact mechanisms remain poorly understood. We have designed and synthesized a novel fluorescent tamoxifen derivative, FLTX1, and characterized its biological and pharmacological activities. Using confocal microscopy, we demonstrate that FLTX1 colocalizes with estrogen receptor α (ERα). Competition studies showed that FLTX1 binding was totally displaced by unlabeled tamoxifen and partially by estradiol, indicating the existence of non-ER-related triphenylethylene-binding sites. Ligand binding assays showed that FLTX1 exhibits similar affinity for ER than tamoxifen. FLTX1 exhibited antiestrogenic activity comparable to tamoxifen in MCF7 and T47D cells transfected with 3xERE-luciferase reporter. Interestingly, FLTX1 lacked the strong agonistic effect of tamoxifen on ERα-dependent transcriptional activity. Additionally, in vivo assays in mice revealed that unlike tamoxifen, FLTX1 was devoid of estrogenic uterotrophic effects, lacked of hyperplasic and hypertrophic effects, and failed to alter basal proliferating cell nuclear antigen immunoreactivity. In the rat uterine model of estrogenicity/ antiestrogenicity, FLTX1 displayed antagonistic activity comparable to tamoxifen at lower doses, and only estrogenic uterotrophy at the highest dose. We conclude that the fluorescent derivative FLTX1 is not only a suitable probe for studies on the molecular pharmacology of tamoxifen, but also a potential therapeutic substitute to tamoxifen, endowed with potent antiestrogenic properties but devoid of uterine estrogenicity.
Synthesis of Tamoxifen-Artemisinin and Estrogen-Artemisinin Hybrids Highly Potent Against Breast and Prostate Cancer
Fr?hlich, Tony,Mai, Christina,Bogautdinov, Roman P.,Morozkina, Svetlana N.,Shavva, Alexander G.,Friedrich, Oliver,Gilbert, Daniel F.,Tsogoeva, Svetlana B.
, p. 1473 - 1479 (2020/07/06)
In the search for new and effective treatments of breast and prostate cancer, a series of hybrid compounds based on tamoxifen, estrogens, and artemisinin were successfully synthesized and analyzed for their in vitro activities against human prostate (PC-3) and breast cancer (MCF-7) cell lines. Most of the hybrid compounds exhibit a strong anticancer activity against both cancer cell lines – for example, EC50 (PC-3) down to 1.07 μM, and EC50 (MCF-7) down to 2.08 μM – thus showing higher activities than their parent compounds 4-hydroxytamoxifen (afimoxifene, 7; EC50=75.1 (PC-3) and 19.3 μM (MCF-7)), dihydroartemisinin (2; EC50=263.6 (PC-3) and 49.3 μM (MCF-7)), and artesunic acid (3; EC50=195.1 (PC-3) and 32.0 μM (MCF-7)). The most potent compounds were the estrogen-artemisinin hybrids 27 and 28 (EC50=1.18 and 1.07 μM, respectively) against prostate cancer, and hybrid 23 (EC50=2.08 μM) against breast cancer. These findings demonstrate the high potential of hybridization of artemisinin and estrogens to further improve their anticancer activities and to produce synergistic effects between linked pharmacophores.
NOVEL COMPOUNDS AND USES THEREOF
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Paragraph 0236-0238, (2018/02/21)
The present disclosure relates to novel compounds, pharmaceutical compositions containing such compounds, and their use in prevention and treatment of estrogen-related diseases and conditions.
