Synthesis and bio-evaluation of novel 7-hydroxy coumarin derivatives via Knoevenagel reaction

Mark Manidhar Darla,Krishna Misra,Cirandur Suresh Reddy,N. Baktavathsala Reddy,Manoj Kumar Srivash,Ch. Syama Sundar,K. Umamaheswara Rao,K. Adeppa,Balam Sateesh Krishna

doi:10.1007/s11164-013-1258-1

Abstract

Coumarin and 7-hydroxy coumarins have great significance as natural fragrances, having a characteristic odour like vanilla beans and their hydroxy position at 7 has importance in biosynthesis. Treatment of 8-formyl-7-hydroxy coumarin with N,N-disubstituted cyano acetamides in the presence of piperidine afforded novel 8-substituted-7-hydroxy coumarin derivatives. Their structures were characterized by IR, 1H, 13C NMR, mass spectral and elemental analysis data. Two out of these 12 compounds, i.e. 2-Cyano-3-(7-hydroxy-2-oxo-2H-chromen-8-yl)-N-[2-(2-methoxy-phenoxy)-ethyl]-acrylamide and 2-Cyano-N-(2,5-dihydro-thiazol-2-yl)-3-(7-hydroxy-2-oxo-2H-chromen-8-yl)-acryl amide showed enhanced in vitro antifungal activity against Candida albicans and Aspergillus niger vis-a-vis standard, i.e. fluconazole, and enhanced in vitro antibacterial activity against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa vis-a-vis standard, i.e. norfloxacin. .

Highlights

O coumarin OH7-Hydroxy coumarinThe parent molecule of coumarin derivatives is the simplest compound of a large class of naturally occurring phenolic substances made of fused benzene and apyrone rings [1]
Their structures were characterized by IR, 1H, 13C NMR, mass spectral and elemental analysis data. Two out of these 12 compounds, i.e. 2-Cyano-3-(7-hydroxy-2-oxo-2H-chromen-8-yl)-N-[2-(2-methoxy-phenoxy)-ethyl]acrylamide and 2-Cyano-N-(2,5-dihydro-thiazol-2-yl)-3-(7-hydroxy-2-oxo-2H-chromen8-yl)-acryl amide showed enhanced in vitro antifungal activity against Candida albicans and Aspergillus niger vis-a-vis standard, i.e. fluconazole, and enhanced in vitro antibacterial activity against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa vis-a-vis standard, i.e. norfloxacin
To develop a general method for the synthesis of 8-Formyl-7-hydroxy coumarin derivatives, experiments were conducted by reacting 8-Formyl-7-hydroxy coumarin with N,N-disubstituted cyano acetamides in the presence of catalytic amounts of piperidine at reflux temperature for 5 h, and N,N-disubstituted cyano acetamides were prepared by reacting corresponding amines with ethyl cyano acetate at reflux temperature for 5 h

Summary

Introduction

The parent molecule of coumarin derivatives is the simplest compound of a large class of naturally occurring phenolic substances made of fused benzene and apyrone rings [1]. Coumarin itself and 7-hydroxycoumarin have been reported to inhibit the proliferation of a number of human malignant cell lines in vitro [2–5], and have demonstrated activity against several types of animal tumors [6–10]. Coumarin is a natural substance that has shown anti-tumor activity in vivo, with the effect believed to be due to its metabolites (e.g., 7-hydroxycoumarin). These compounds have been reported in clinical trials to demonstrate activity against prostate cancer, malignant melanoma, and metastatic renal cell carcinoma [11–13]. 7-hydroxy coumarin was condensed with N,N-dialkyl substituted cyano acetamide derivatives to get the novel knoevenagel products, which are expected to be biologically active

Methods

Results

Conclusion