Synthesis and Structure–Antitumor Activity Relationship of Sulfonyl 5-Fluorouracil Derivatives

Abstract

Novel sulfonyl 5-fluorouracil derivatives 2 (5-fluoro-1-(arylsulfonyl)pyrimidine-2,4(1H,3H)-diones) have been synthesized via the reaction of 5-fluorouracil with sulfonyl chloride. Their chemical structures were confirmed by means of ¹H NMR, ¹³C NMR, IR, mass spectra, and elemental analyses, and, in the case of 2a, its structure was established by single crystal X-ray diffraction. Some of the compounds were assayed for anticancer (HL-60 and BEL-7402 cells) activities. Structure–activity relationship (SAR) analysis discovered that the anticancer activity was related to the configuration, and that electron-withdrawing groups at 2-position or 4-position on the aryl group of arylsulfonyl derivatives of 5-fluorouracil could enhance the anticancer activity against the BEL-7402 cells.

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Keywords:

• Anticancer activities
• crystal structure
• sulfonyl 5-fluorouracil derivatives

Acknowledgments

We acknowledge financial support from the National Natural Science Foundation of China (No. 20571057), the Wenzhou Technology Project Foundation of China (No. S20060026), and the National Center for Drug Screening, Shanghai, China, for evaluation of antitumor activities.