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Triphenylethylene Analogs As Therapeutic Agents for Breast Cancer

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Triphenylethylene Analogs As Therapeutic Agents for Breast Cancer Xavier University of Louisiana XULA Digital Commons Festival of Scholars 2021 Triphenylethylene Analogs as Therapeutic Agents for Breast Cancer Holly Honore Department of Chemistry, Xavier University of Louisiana Bouri Kang Ph.D Department of Chemistry, Xavier University of Louisiana Florastina Payton-Stewart Ph.D Department of Chemistry, Xavier University of Louisiana Follow this and additional works at: https://digitalcommons.xula.edu/xula_fos Part of the Chemistry Commons, and the Oncology Commons Recommended Citation Honore, Holly; Kang, Bouri Ph.D; and Payton-Stewart, Florastina Ph.D, "Triphenylethylene Analogs as Therapeutic Agents for Breast Cancer" (2021). Festival of Scholars. 13. https://digitalcommons.xula.edu/xula_fos/13 This Book is brought to you for free and open access by XULA Digital Commons. It has been accepted for inclusion in Festival of Scholars by an authorized administrator of XULA Digital Commons. For more information, please contact [email protected]. Triphenylethylene Analogs as Therapeutic Agents for Breast Cancer Holly Honore, Bouri Kang, Ph.D., Florastina Payton-Stewart Ph.D. Department of Chemistry, Xavier University of Louisiana ABSTRACT HYPOTHESIS FUTURE GOALS The most frequently diagnosed cancer for women is By using molecular modeling, microwave and traditional chemistry, I will be able to carry out my hypothesis, which is to My goal is to focus on fully understanding the breast cancer. Around 5–10% of diagnosed breast cancer design and synthesize irreversible ER inhibitors using the core structure of tamoxifen, which is triphenylethylene. reactions that I will use to carry out the synthesize cases are metastatic and close to 30% of patients with triphenylethylene analogs by using the synthetic early-stage disease will go on to relapse with metastatic disease (1). Hormone receptor-positive breast cancer scheme (see Figure 4). I will work to make sure that I makes up 70% of breast cancer cases. The first-line can operate the machines in our research laboratory treatment for breast cancer is endocrine therapy. and perform calculations for the synthetic scheme. I Endocrine therapy, also known as hormone therapy, will also make sure we have all the required materials adds, blocks, or removes hormones to treat the disease. to carry out the proposed synthesis. The analogs will There are two types of endocrine therapy for breast be chemically analyzed using TLC, NMR, and GC. The cancer. One type is drugs that prevent estrogen and TRIPHENYLETHYLENE TAMOXIFEN analogs will be biologically evaluated by collaborators progesterone from being available for breast cancer cells and/or core facilities at Xavier. to grow. The other type of endocrine therapy is drugs or surgery to keep the ovaries from making hormones. SYNTHESIS OF TRIPHENYLETHYLENE ANALOGS REFERENCES There are several different types of treatment options (see Figure 1). While we have made many advances in (1)Redig, A. J.; McAllister, S. S. Breast Cancer as a Systemic Disease: A View of Metastasis. J. Intern. Med. 2013, 274 (2), 113–126. this area, a significant number of patients develop https://doi.org/10.1111/joim.12084. (accessed July 5 2020). endocrine resistance, prompting the need for newer (2) Shen, L.-S.; Jin, X.-Y.; Wang, X.-M.; Tou, L.-Z.; Huang, J. Advances in therapeutic agents (2). Endocrine and Targeted Therapy for Hormone-Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Chin Med J (Engl) 2020, 133 (9), 1099–1108. CURRENT METHODS OF TREATMENT https://doi.org/10.1097/CM9.0000000000000745. (accessed July 5 2020). (3)Tamoxifen: Uses, Side Effects, and More https://www.breastcancer.org/treatment/hormonal/serms/tamoxifen (accessed Jul 5, 2020). (4)Fan, W.; Chang, J.; Fu, P. Endocrine Therapy Resistance in Breast Cancer: Current Status, Possible Mechanisms and Overcoming Strategies. Future Med Chem 2015, 7 (12), 1511–1519. https://doi.org/10.4155/fmc.15.93 (accessed Jul 5, 2020). Figure 2: The places that are circled in blue are the four places that we plan to make structural modifications to (5)D’Souza, A.; Spicer, D.; Lu, J. Overcoming Endocrine Resistance in Metastatic triphenylethylene. Hormone Receptor-Positive Breast Cancer. Journal of Hematology & Oncology 2018, 11 (1), 80. https://doi.org/10.1186/s13045-018-0620-6 (accessed Jul 5, SYNTHESIZED ANALOGS 2020). ACKNOWLEDGEMENTS Figure 1: Current methods of treatment, mechanism of action, and Work reported in this presentation is supported by the names. NIH BUILD program under the grant number BACKGROUND TL4GM118968. Endocrine resistance is when a patient relapses on Special thanks to Dr. Payton-Stewart, all BUILD PIs, endocrine therapy. The first-line treatment for breast Figure 3: The Payton-Stewart research laboratory has successfully synthesized the triphenylethylene analogs 1 and 1a. Camri Eaton, Jonah Brown, and Deeuatrail Nichols for cancer is Tamoxifen (Nolvadex). Tamoxifen has been used all their help and support this summer. in the management of metastatic hormone receptor- SYNTHESIS OF TRIPHENYLETHYLENE ANALOG 1 positive early, locally advanced, and metastatic breast cancer for over 40 years. Tamoxifen works by binding to the estrogen receptor in the cancer cell, blocking estrogen from attaching to the receptor. This mechanism of action slows or stops the growth of the tumor by preventing the cancer cells from getting the hormones they need to grow. The problem with Tamoxifen is patients develop resistance and it has been known to cause endometrial cancer. The development of endocrine resistance has prompted the need to develop novel therapeutic agents to overcome endocrine resistance. Figure 4: The image shows the synthetic scheme of triphenylethylene analog. .
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