Abstract

Salam W. Ahjel, Saif M. Hassan, Sinan F. Hussein, Najah R. Hadi, Samir M. Awad.

Many studies have been focused on the cancer therapeutics through studying the cytotoxic activities of different compounds such as synthetic, semi synthetic and plant constituents, our study deal with synthesis of novel 2-Thiouracil-5-sulfonamide derivatives. The target compounds were prepared by chlorosulfonation of 2-thiouracil using chlorosulfonic acid at 120oC giving 2-Thiouracil-5-sulfonyl chloride 2, which in turn was reacted with p-halobenzyl amines namely; p-fluoro, p-chloro and p-bromo analogues respectively to yield sulfonamides 3a-c. Moreover, sulfonamides 3a-c was chlorinated by POCl3/PCl5 mixture to afford chloro derivatives 4a-c. In addition, the latter were hydrazinolysed by NH2NH2 yielding hydrazine derivatives 5a-c. In another pathway, hydrazine derivatives 5a-c was condensed with benzaldehyde yielding Schiff’s bases 6a-c. Furthermore, hydrazine derivatives 5a-c was reacted with phenyl isocyanine affording compounds 7a-c. The newly synthesized compounds were screened for in vitro anticancer activity against A-2780 ovarian and MCF-7 breast carcinoma cells. They showed variable response, the most active compounds were hydrazine carbothioamides 7a-c which showed wide spectrum activity against the two cell lines. Moreover, the prepared compounds were formulated as water soluble tablets in an attempt to improve the bioavailability of thiouracil containing compounds. The tablets were subjected to some quality control testing.