Structure activity relationship studies on the glycosides, and alkylidenethiosemicarbazide compounds as tyrosinase inhibitors

Tyrosinase is a copper-containing enzyme widely distributed in nature. It catalyzes two distinct reactions, the hydroxylation of a monophenol (monophenolase activity) and the oxidation of odiphenols to o-quinones (diphenolase activity)[1]. Tyrosinase is responsible, not only for melanization in animals, but also for browning in plants. The accumulation of an excessive level of epidermal pigmentation can cause some dermatological disorders associated with freckles, melasma, ephelide and senile lentigines. Therefore, the control of the tyrosinase is important in relation to browning control of vegetables and fruits, and potent tyrosinase inhibitors have also become increasing important in medicinal and cosmetic products in relation to hyperpigmentation. Nowadays, tyrosinase inhibitors are thought to be clinically useful for the treatment of some dermatological disorders associated with melanin hyperpigmentation [2], and useful in cosmetic products and food industry. In this work quantitative structure and activity relationship of some tyrosinase inhibitors was investigated by QSAR methods. The structure of molecules were optimized by Hyperchem in gas phase and solution and related descriptors obtained by Dragon. Multiple linear regression was performed on descriptors. The best model selected and correspond equation was derived. The interaction between ligand and enzyme was studied by Autodock. The results showed that the logIC50 varies as follow: logIC50 = -4.370-0.038 (PSA) + 0.131 (Ss) - 0.012 (AGDD) + 0.048 (HE) R=0.912 Where, PSA, Ss and HE, are fragment-based polar surface area, sum of Kier-Hall electrotopologicalstates, average geometric distance degree and hydration energy, respectively.