Synthesis of New 5-Fluorouracil Derivatives as Possible  Prodrug for Targeting Cancer

Hassan Mohammad, Mohammad

	Synthesis of New 5-Fluorouracil Derivatives as Possible Prodrug for Targeting Cancer
Al-Mustansiriyah Journal of Science
Article 1, Volume 20, Issue 5, 2009, Pages 51-68
Author
Mohammad Hassan Mohammad
Abstract
A promising approach to improve the cancer cell selective properties of 5-fluorouracil is the chemical transformation into reversible derivatives (produgs) which are converted to the parent drug by virtue of enzymatic or chemical hydrolysis within the cancer tissue. In the present study, three derivatives of 5-fluorouracil has been designed to be synthesized as 5-fluorouracil prodrugs to selectively deliver the drug into the cancer cells and these were: The generation of the target compounds II, V, and VI were accomplished following multi step reaction procedures. The reaction and purity of the products were checked by TLC, the structure of the final compounds and their intermediates were confirmed by their melting points, infra red spectroscopy, ultra violate spectroscopy and elemental microanalysis. The hydrolysis of compounds II, V, and VI in aqueous buffer solution of pH 6 and pH 7.4 were studied. Compounds II and V had acceptable rate of hydrolysis at pH 6 (t ½=50.3 min and t½=52.4 min respectively) and enough stability at pH 7.4(t½=512.29 min and t½=260.32 min respectively); therefore these two compounds can selectively deliver 5-fluorouracil into the tumour cells which have pH approximate to(6). On the other hand, compound VI had lower rate of hydrolysis at pH 6 and enough rate of hydrolysis at pH 7.4 (t½=104.4 min and t½81.6 min respectively) . According to the results mentioned above, compounds II and V can be good candidates as 5-fluorouracil prodrugs that can selectively deliver the parent drug into the cancer cells by the effect of pH.

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