Efficient Microwave-Assisted Solvent-Free Synthesis and Molecular Docking Studies of 2-pyridone derivatives as Anticancer Agents and Evaluation of Cytotoxic Effects

Magda Hassan Abdellattif

doi:10.24297/jac.v12i4.2175

Abstract

Introduction: A green protocol will be used to synthesize a novel series of 3-cyano-5- arylazo-pyridones (9a-c) and (10d-i). Methodology: Structures of the new products will be confirmed on the basis of spectroscopic data (FT-IR, 1D, NMR) as well as alternative synthetic routes, anticancer cell-line will be investigated and also molecular docking studies will be applied. Results: The activity against different cancer cell-line will be studied. Compounds with electron withdrawal group showed the highest activities.

Highlights

A green protocol will be used to synthesize a novel series of 3-cyano-5- arylazo-pyridones (9a-c) and (10d-i)
It was found that cancer is a fatal disease and it is the 2nd one around the world after heart failure, Pyridone derivatives, pyridone nucleus containing compounds, and most of pyridine skeleton compounds are very important for researchers in chemistry as well as biology because large number of these compounds are found in nature, especially 2-pyridone ring system which imposes a great spectrum of biological activities as anticancer drugs, antibacterial, and antimicrobial, antituberculosis, and many other biological activities.[1,2]
Other isomers of 2-pyridone is 4-pyridone which has magnetic properties which can be used in synthesis of liquid crystals and has antioxidant properties which can be used as drug in hyperglycemia[4]

Summary

Introduction

A green protocol will be used to synthesize a novel series of 3-cyano-5- arylazo-pyridones (9a-c) and (10d-i). Guareschi-Thorpe described a general method by condensation of dicarbonyl compounds with cyanoacetamide 5, 6 which is about 3-2 type of condensation leads to formation of pyridone.[7]. In most of these approaches, variety of 2-pyridone derivatives has been synthesized through introducing different functional groups on the pyridone ring. Development of potent and effective anticancer drugs is one of the more pressing goals of current medicinal chemistry.[8,9] Various nucleosides have been reported to have important biological properties.[10] In particular, 4-Amino-3-fluoro-1-(β-D-ribofuranosyl)-2(1H)-pyridone 1 inhibits the growth of HL-60 lymphoid leukemia cells with IC50 =1.07 x 10-5 M, while 2'-deoxy analogue of 1 is active against lymphoid leukemia L1210 cells. 3-(4 ,7 -Dimethyl benzoxazol-2 -yl)amino-5-ethyl-6-methyl pyridine-2(1H)-one 2 and its 4,7-dichloro analogue have been reported to inhibit the spread of HIV1 infection by 95% in MT4 cell culture and were selected for clinical trials as antiviral agents. 4-Benzylpyridone 10 has been shown to possess potent HIV-1 specific reverse transcriptase inhibitor properties.[12] (figure 1)

Objectives

Methods

Results