Abstract 2515: Synthesis of substituted chromone-2-phenylcarboxamides as anti-breast cancer agents

Abstract

Abstract Breast cancer is one of the most commonly diagnosed cancers and causes the second leading cancer deaths in women. The overall survival rate of breast cancer patients has substantially increased during the last decades due to early tumor detection. Unfortunately, the recovery rate of advanced breast cancer by current available drug treatment is still unacceptably low. Although chemotherapy is the main stay of cancer treatment at present, most of the drugs cause general toxicity to any proliferating cells and tend to severely limit the therapeutic values of these drugs. In an attempt to overcome these problems, the synthesis of new anti-breast cancer agents with unique mechanisms of action was developed. Chromones are benzannulated oxygen containing heterocyclic compounds widely distributed in nature that have a -pyrone ring. The chemical core of chromone has been classifies as a privileged structures in drug discovery, due to its uses in a wide variety of pharmacologically active compounds such as anti cancer, anti-HIV, antibacterial and anti-inflammatory agents. Based on these considerations, we attempted the synthesis of novel substituted chromone-2-phenylcarboxamides as anti-breast cancer agents. The starting material chromones-2-carboxylic acid was obtained by the hydrolysis reaction of ethyl esters with the mixture of glacial acetic acid and concentrated HCl (2:1v/v) and the mixture was heated to reflux for 12 h. The acids were obtained in 70-80% yields. A suspension of substituted chromone-2-carboxylic acid in DMF was added to substituted anilines, in the presence of diphenylphosphorylazide and triethylamine. The reaction mixture was stirred at room temperature for 24 h, which furnished the target compounds i.e., substituted chromone-2-phenylcarboxamides. These compounds were evaluated for their cytotoxic effects on MCF-7 ER+ve breast cancer cells, MDA-MB-231 ER-ve breast cancer cell lines and Ishikawa cells using the CellTiter-Glo luminescent cell viability assay. N-(4-hydroxyphenyl)-5,7-dimethoxy-4-oxo-4H-chromene-2-carboxamide showed the most potent cytotoxicity with an IC50 values of 29.5 and 25.7 µM on MCF-7 and Ishikawa cell lines, respectively. This research was supported by National Center for Research Resources and the National Institute of Minority Health and Health Disparities of the National Institutes of Health through Grant Number 8 G12MD007582-28. Citation Format: Kinfe Ken Redda, Madhavi Gangapuram, Mohammad A. Ghaffari, Suresh Eyunni. Synthesis of substituted chromone-2-phenylcarboxamides as anti-breast cancer agents. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2515. doi:10.1158/1538-7445.AM2014-2515