Abstract 514: Design and synthesis of substituted tetrahydroisoquinoline derivatives as an antibreast cancer agents
Authors: Redda Kinfe Ken , Gangapuram Madhavi , Zhang Wang , Eyunni Suresh 
Published: September 2020

Breast cancer is one of the most commonly diagnosed cancers and causes the second leading cancer deaths in women. In 2019, the American Cancer Society (ACS) reported 268,600 new cases of breast cancer in the U.S. and about 41,760 women were expected to die from the disease. Unfortunately, the recovery rate from advanced breast cancer using the current available drug treatment is still unacceptably low. In recent years, small molecule therapeutics gained a substantial popularity as they revolutionized the whole drug discovery and development process. Novel small molecule cancer drugs that are rationally designed on advanced chemical and biotechnological computations are likely to exceed the efficacy of many existing drugs. Our target, the tetrahydroisoquinoline (THIQ) core structure is an important pharmacophore in natural products. The THIQ moieties were reported to be selective estrogen receptor modulators (SERMs) and microtubule disruptors and also possess potent cytotoxic activities such as antitumor and antimicrobial activities. In our laboratory, N-amination of substituted isoquinolines by the aminating agent, O-mesytelenesulfonylhydroxylamine and treated with acyl chlorides led to the formation of ylides. The ylides were reduced using sodium borohydride to give the desired substituted tetrahydroisoquinolines in moderate to good yields. The synthesized compounds were characterized using NMR and elemental analysis. The novel compounds were evaluated in vitro for antiproliferative activity on MCF-7 (ER +ve), MDA-MB-231 (ER -ve) and Ishikawa (endometrial) cancer cell lines. Compound 4-amino-N-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)benzamide showed significant cytotoxic activity (IC50 values 2.7, 9.51 and 1.05 µg/mL) on MCF-7, MDA-MB-231 and Ishikawa cell lines, respectively in comparison to Tamoxifen (8.99, 10.64, 9.59 µg/mL, respectively). These results indicated that novel substituted THIQ derivatives can be considered as potential and effective cytotoxic agents against MCF-7, MDA-MB-231 and Ishikawa cell lines.

This research was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under the Award Number U54 MD007582. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This research was also made possible by Grant Numbers U54CA233396, U54CA233444, and U54CA233465 from the National Institutes of Health (NIH), National Cancer Institute (NCI). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCI.

Citation Format: Kinfe Ken Redda, Madhavi Gangapuram, Wang Zhang, Suresh Eyunni. Design and synthesis of substituted tetrahydroisoquinoline derivatives as an antibreast cancer agents [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 514.