SYNTHESIS OF MUTUAL PRODRUG OF P-AMINO SALICYLIC ACID (PAS) AND ISONIAZID(INH), WITH POSSIBLE ENHANCEMENT PHYSICOCHEMICAL PROPERTIES

Tuberculosis is one of the most widespread disease in the world, and can be deadly in patients with AIDS worldwide. The course of treatment is long (3-9) months, often need combination therapy to decrease microbial resistance, some of these drugs have serious side effects and undesirable physicochemical properties like, gastric irritation, short T1/2 (pas), hepatic toxicity and extensive metabolism by the liver (INH), through N-acetyl transferase enzyme. So by using this approach we hope reduction of gastrointestinal toxicity of PAS and reduction of intestinal acetylation of Isoniazid. This drug was synthesized by amidation of free amine group of INH with free carboxyl group of glycine from one side and amidation of carboxyl group of PAS after protection of it, and amino group of glycine from other side, here amidation was done by using coupling agent (DCC) using conventional solution method and it was identified by the following methods: melting point, thin layer chromatography (TLC), infrared spectroscopy (IR) and the elemental analysis(CHN). The synthesized compound showed better partition coefficient compared with the original apromoiety (PAS,INH).