Khan Mahmud Tareq Hassan, Choudhary Muhammad Iqbal, Khan Khalid Mohammed, Rani Mubeen
Pharmacology Research Laboratory, Faculty of Pharmaceutical Sciences, University of Science and Technology, Chittagong, Bangladesh.
Bioorg Med Chem. 2005 May 16;13(10):3385-95. doi: 10.1016/j.bmc.2005.03.012.
Here the tyrosinase inhibition studies of library of 2,5-disubstituted-1,3,4-oxadiazoles have been reported and their structure-activity relationship (SAR) also have been discussed. The library of the oxadiazoles was synthesized under the microwave irradiation and was structures of these were characterized by different spectral techniques. From this study it could be concluded that for a better inhibition of tyrosinase, electronegative substitution is essential as most probably the active site of the enzyme contain some hydrophobic site and position is also very important for the inhibition purposes due to the conformational space. The electronegativity of the compounds is somewhat proportional to the inhibitory activity. The compound 3e (3'-[5-(4'-bromophenyl)-1,3,4-oxadiazol-2-yl]pyridine) exhibited most potent (IC50 = 2.18 microM) inhibition against the enzyme tyrosinase which is more potent than the standard potent inhibitor L-mimosine (IC50 = 3.68 microM). This molecule can be the best candidate as a lead compound for further development of drug for the treatments of several skin disorders.
本文报道了2,5-二取代-1,3,4-恶二唑库的酪氨酸酶抑制研究，并讨论了其构效关系（SAR）。恶二唑库在微波辐射下合成，其结构通过不同的光谱技术进行表征。从这项研究可以得出结论，为了更好地抑制酪氨酸酶，电负性取代是必不可少的，因为酶的活性位点很可能包含一些疏水位点，并且由于构象空间的原因，位置对于抑制目的也非常重要。化合物的电负性与抑制活性在一定程度上成正比。化合物3e（3'-[5-(4'-溴苯基)-1,3,4-恶二唑-2-基]吡啶）对酪氨酸酶表现出最有效的抑制作用（IC50 = 2.18 microM），比标准强效抑制剂L-含羞草碱（IC50 = 3.68 microM）更有效。该分子可作为先导化合物，用于进一步开发治疗多种皮肤疾病的药物。
