Abstract 1889: Synthesis of substituted tetrahydroisoquinoline chromone-2-carboxamidesas anti-breast cancer agents

Abstract

Abstract According to World Health Organization, breast cancer is second leading cause of mortality among women, accounting for 12% of all new annual cancer cases worldwide. In 2021, the American Cancer Society (ACS) reported that there will be 281,550 new cases of breast cancer in U.S. and about 43,600 women will be expected to die from the disease. Unfortunately, the recovery rate from advanced breast cancer by current available drug treatment is unacceptably low. Hence, there is an urgent need to develop more effective and less toxic small drug molecules with a unique mechanism of action. Chromones are benzannulated oxygen containing heterocyclic compounds that are widely distributed in nature and have a gamma-pyrone ring. Natural and synthetic molecules having chromone scaffold displayed interesting pharmacological activities such as anti-cancer, anti-HIV, antiviral and anti-inflammatory activities with low toxicity. In continuation of our current research work, we report the synthesis of substituted tetrahydroisoquinoline chromone carboxamides. Modifications of the chromone scaffold at pyrone ring by attaching substituted tetrahdyrosioquinolines were carried out to prepare compounds with a potential of acting as anti-breast cancer agents. The starting material, substituted chromone-2-carbonyl chloride was obtained by the acylation reaction of corresponding carboxylic acids using phosphorous pentachloride in dry cyclohexane. An equimolar amount of acyl chloride was slowly added to a stirred solution of corresponding substituted N-aminoisoquinoline in dry THF, in the presence of triethyl amine and refluxed at 70 degrees C that led to the formation of the ylides. The ylides were reduced using sodium borohydride to yield the desired substituted tetrahydroisoquinoline chromone-2-carboxamides in moderate to good yields. The synthesized compounds were characterized by NMR, IR, and elemental analysis. These compounds were evaluated for their cytotoxic effects on MBA-MB-231 ER-ve breast cancer cell lines using a Synergy HTX multi-mode reader (Bio-Tek, Winooski, VT, USA) with excitation/emission wavelength settings at 550/580. Compound N-(3,4-dihydroisoquinolin-2-(1H0-yl)-6-methyl-4-oxo-4H-1-benzopyran-2-carboxmaide showed the most potent cytotoxicity with an IC50 value 0.82 microgram/mL on MDA-MB-231 cell line. 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. Citation Format: Kinfe Ken Redda, Madhavi Gangapuram, Elizabeth Mazzio, Ramesh Badisa, Suresh Eyunni, Karam F. A. Soliman. Synthesis of substituted tetrahydroisoquinoline chromone-2-carboxamidesas anti-breast cancer agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1889.