Abstract 2229: Synthesis of heterocyclic compounds as anticancer agents.
Authors: Redda Kinfe Ken , Gangapuram Madhavi , Ghaffari Mohammad A. , Eyunni Suresh , Mateeva Nelly , Mochona Bereket 
Published: August 2014

Cancer is a very complex disease, linked with different initiating causes, cofactors and promoters, and several types of cellular damages. There is a strong correlation between chronic inflammatory conditions in a particular organ and cancer specific to that organ. The longer the inflammation persists, the higher the risk of associated carcinogenesis. Drug discovery process has changed dramatically over the past decade as there is an increasing demand to obtain more drug candidates and decrease attrition during drug development. Chromone scaffold [(4H)-1-benzopyran-4-one] has been recognized as a pharmacophore of a large number of bioactive molecules of either natural or synthetic origin. Until now, numerous biological effects such as anti-inflammatory, antitumoral, and antimicrobial activities especially in popular medicine, have been attributed to this benzo-γ-pyrone nucleus. Compounds of this type also possess inhibition properties towards different enzymes such as oxidoreductases, kinases, tyrosinases, lipoxygenases and cyclooxygenases. Chemotherapeutic agents like tetrahydropyridine (THP) analogs exhibit diverse biological activities like analgesic and anti-inflammatory effects. Our earlier research results indicated that some of the THP derivatives showed COX-2 inhibition and anti-inflammatory activities on rat paw edema assay studies. Incorporation of THP moiety might enhance biological activity of the chromone derivatives. Herein, we report the synthesis of substituted N-(5,6-dihydropyridin-1-(2H)-yl)-4-oxo-4H-chromene-2-carboxamide as anticancer and anti-inflammatory agents.

The starting material 4-oxo-4H-chromene-2-carbonyl chloride was obtained by the reaction of 4-oxo-4H-chromene-2-carboxylic acid, dissolved in 1,2-dichloroethane and SOCl2 containing few drops of DMF under reflux for 4h. The crude acid chloride obtained by removing the excess of SOCl2 and solvent under vaccum, was used immediately for next step. Reaction of the acid chloride with substituted N-amino pyridinium salt in anhydrous tetrahydrofuran gave stable ylides. This was followed by reduction with sodim borohydride in absolute ethanol, which furnished the target compound. These compounds were evaluated for their cytotoxic effects on MCF-7 ER positive breast cancer cells, MDA-MB ER receptor negative breast cancer cells, and Ishikawa cell line using the CellTiter-Glo (CTG) luminescent cell viability assay. N-(4-tert-butyl-5,6-dihydropyridin-1(2H)-yl)-6-chloro-7-methyl-4-oxo-4H-chromene-2-carboxamide showed the cytotoxicity with an IC50 values of 73.28 μM on MDA-MB-231 cell lines.

This research was supported by the 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, Nelly Mateeva, Bereket Mochona. Synthesis of heterocyclic compounds as anticancer agents. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2229. doi:10.1158/1538-7445.AM2013-2229