Synthesis of novel pyridin-2-(1H)-one, benzopyran-2(1H)-one, and quinolin-2(1H)-one derivatives & sar study of their anticancer and antiplatelet activities

Abstract

The thesis is divided into three chapters, i.e. Chapter I, Chapter II, and Chapter III. Compounds classified as Heterocyclic probably constitute the largest and most varied family of organic compounds. Every carbocyclic compound, regardless of structure and functionality, may in principle be converted into a collection of heterocyclic analogs by replacing one or more of the ring carbon atoms with different element. Even if we restrict our consideration to oxygen, nitrogen and sulfur (the most common heterocyclic elements), the permutations and combinations of such a replacement are numerous. Among these pyridin- 2(1H)-one, benzopyran-2(1H)-one and quinolin-2(1H)-one are important heterocyclic compounds with great applicability in medicinal chemistry and these core structures can be found in compounds with various biological / medicinal applications. The work presented in the Chapter I described the design and synthesis of novel pyridin-2(1H)-one derivatives and evaluation of their anticancer activity against three human cancer cell lines namely human ovarian adenocarcinoma cells (SK-OV-3), human breast carcinoma cells (MCF-7), and human blood cancer cells (CCRF-CEM). 2-Pyridone analogs are elegant targets in organic synthesis due to their potential clinical applicability and various biological activities. Studies by various groups using different substitution on pyridin-2(1H) one showed that these are potent for various biological activities such as antimicrobial, antiviral, anti-inflammatory, antimalarial, antioxidant and anticancer. As part of our ongoing efforts to synthesize structurally novel and bioactive heterocyclic compounds, we became interested in synthesizing N-substituted derivatives of benzoylpyridin-2-(1H)-ones to explore their anticancer activity. The synthesis of these novel target compounds were achieved by reacting (E)-ethyl 3-(7-hydroxy-4-oxo-4H-chromen-3- yl)acrylate, (E)-ethyl 3-(6-hydroxy-4-oxo-4H-chromen-3-yl)acrylate, (E)-ethyl 3-(7- methoxy-4-oxo-4H-chromen-3-yl)acrylate