Saeed Aamer, Ur-Rehman Sajid, Channar Pervaiz Ali, Larik Fayaz Ali, Abbas Qamar, Hassan Mubashir, Raza Hussain, Seo Sung-Yum
Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan.
Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, Chungnam, Republic of Korea.
Drug Res (Stuttg). 2017 Oct;67(10):596-605. doi: 10.1055/s-0043-113832. Epub 2017 Jul 3.
A series of acylthioureas was synthesized and their inhibitory effects on the DPPH and jack bean urease were evaluated. The results showed that all of the synthesized compounds exhibited significant jack bean urease inhibitory activities. Especially, 1-(4-chlorophenyl)-3 palmitoylthiourea bearing 4-chloro substituted phenyl ring exhibited the most potent tyrosinase inhibitory activity with an IC value 0.0170 μM compared to the IC value of 4.720 μM of thiourea used as standard. The inhibition mechanism analyzed by Lineweaver-Burk plots revealed that the type of inhibition of compound on tyrosinase was noncompetitive. The docking study against jack bean urease enzyme was also performed to determine the binding affinity of the compounds. The compounds 4c and 4e showed the highest binding affinity with the active binding site of tyrosinase. The initial structure activity relationships (SARs) analysis suggested that further development of such compounds might be of interest. The statistics of our results endorses that all compounds and particularly may serve as a structural template for the design and development of novel urease inhibitors Graphical Abstract.
合成了一系列酰基硫脲，并评估了它们对DPPH和刀豆脲酶的抑制作用。结果表明，所有合成化合物均表现出显著的刀豆脲酶抑制活性。特别是，带有4-氯取代苯环的1-(4-氯苯基)-3-棕榈酰硫脲表现出最强的酪氨酸酶抑制活性，IC值为0.0170 μM，而用作标准的硫脲的IC值为4.720 μM。通过Lineweaver-Burk图分析的抑制机制表明，该化合物对酪氨酸酶的抑制类型为非竞争性。还进行了针对刀豆脲酶的对接研究，以确定化合物的结合亲和力。化合物4c和4e与酪氨酸酶的活性结合位点表现出最高的结合亲和力。初步的构效关系（SARs）分析表明，进一步开发此类化合物可能具有意义。我们结果的统计数据支持所有化合物，特别是 可作为设计和开发新型脲酶抑制剂的结构模板。图形摘要。
