A Novel One-Pot and Efficient Procedure for Synthesis of New Fused Uracil Derivatives for DNA Binding

Bothaina A Mousa,Ashraf H Bayoumi,Mohamed G Assy,Samar A El-Kalyoubi,Makarem M Korraa

doi:10.4236/ijoc.2015.51005

Bothaina A Mousa, Ashraf H Bayoumi + Show 3 more

Open Access

https://doi.org/10.4236/ijoc.2015.51005

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Abstract

Hydrazinolysis of 6-chloro-1-methyluracil followed by condensation of the product with different aromatic aldehyde gives the respective hydrazones which undergoes oxidative cyclization using thionyl chloride to obtain pyrazolo[3,4-d]pyrimidines in good yields. On the other hand, nitrosation of 6-aminouracils followed by the reaction with different arylidineanilines gives new xanthine derivatives. Finally, indenopyrrolopyrimidine and indenopteridine are obtained in good yields via the reaction of 6-aminouracils and 5,6-diaminouracil with ninhydrin respectively. The newly synthesized compounds show binding, chelation and fragmentation of the nucleic acid DNA.

Highlights

The importance of fused pyrimidines, common source for the development of new potential therapeutic agents [1] [2], is well known.Fused pyrimidines continue to attract considerable attention because of their great practical usefulness, primarily due to very wide spectrum of biological activities
They compete with the normal substrates, folic acid and dihydrofolate, for the active site on the enzyme dihydrofolate reductase (DHFR) [10]-[12]
B) A mixture of 5,6-diamino-1,3-dimethyluracil hydrochloride (10) (0.2 g, 1.00 mmol) and ninhydrin (0.18 g, 1.00 mmol) in water (15 ml) and few drops of ammonium hydroxide solution was added to adjust pH = 8 was stirred at room temperature for 1 hour

Summary

Introduction

The importance of fused pyrimidines, common source for the development of new potential therapeutic agents [1] [2], is well known. Fused pyrimidines continue to attract considerable attention because of their great practical usefulness, primarily due to very wide spectrum of biological activities. This is evident especially from publications of regular. 5-Fluorouracil [3]-[5] and methotrexate (MTX) [6]-[8] are the oldest antifolate anticancer drugs [9], which are widely used as chemotherapeutic drugs They compete with the normal substrates, folic acid and dihydrofolate, for the active site on the enzyme dihydrofolate reductase (DHFR) [10]-[12]. The existing methods for the preparation of pyrazolopyrimidines are based on heterocyclic hydrazones or hydrazine precursors Pyrimidines and their derivatives are considered to be important for drugs. A series of new pyrimidine fused ring analogs have been synthesized and their biological effects are determined

Chemistry

Biological Evaluation

Conclusion