Synthesis and in vitro Tyrosinase activities of Sulphamethazine derivatives

Abstract

The process of finding new uses of existing drugs is termed drug repositioning or drug repurposing, has been gaining popularity in recent years. Sulfamethazine (SMZ) is an antibacterial sulfur drug which suppresses dihydrofolic acid synthesis. It is used to treat livestock diseases; such as gastrointestinal and respiratory tract infections. During the current study, synthesis and characterization of Sulfamethazine (SMZ) derivatives (3-39) are described. They were synthesized by the reaction ofSulfamethazine drug with a range of acid chlorides. All the compounds were characterized by spectroscopic techniques such as 1H-, 13C-NMR, EI-MS and HRFAB-MS. These derivatives were then evaluated for the first time for their Tyrosinase inhibitory activity by using Mushroom tyrosinase. Among its derivatives, compounds 15-21, 24, and 25 were identified as new compounds. Compounds 3, 4, 5 and 6 were found to be more active (IC50 = 26.9 ± 1.2, 34.3 ± 1.0, 43.1 ± 0.7 and 46.0 ± 1.9 RM respectively) than the standard drug, Kojic Acid (IC50 = 46.9 ± 0.5 uM) against Tyrosinase. Kinetic studies were carried out on the most active members of the series in order to determine their mode of inhibition and dissociation constants. Compounds 3, 4, 5 and 6 were found to be the competitive inhibitors of Tyrosinase. The cytotoxicity of compound 3-39 was also evaluated against the normal mouse fibroblast NIH-3T3 cell line. All the compounds were found to be non-cytotoxic.