新型 1,3,4-噁二唑衍生物的分子对接、计算和抗血栓形成研究。

Molecular Docking, Computational, and Antithrombotic Studies of Novel 1,3,4-Oxadiazole Derivatives.

机构信息

Institute of Chemistry, University of the Punjab, New Campus, Lahore 54590, Pakistan.

Laboratory of Organometallics, Catalysis and Ordered Materials, State Key Laboratory of Advanced Technology for Material Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China.

出版信息

Int J Mol Sci. 2018 Nov 15;19(11):3606. doi: 10.3390/ijms19113606.

A new series of 1,3,4-oxadiazoles derivatives was synthesized, characterized, and evaluated for their in vitro and in vivo anti-thrombotic activity. Compounds (⁻) exhibited significant clot lysis with respect to reference drug streptokinase (30,000 IU), and enhanced clotting time (CT) values (130⁻342 s) than heparin (110 s). High affinity towards 1NFY with greater docking score was observed for the compounds (, , , , and ) than the control ligand RPR200095. In addition, impressive inhibitory potential against factor Xa (F-Xa) was observed with higher docking scores (5612⁻6270) with Atomic Contact Energy (ACE) values (-189.68 to -352.28 kcal/mol) than the control ligand RPR200095 (Docking score 5192; ACE -197.81 kcal/mol). In vitro, in vivo, and in silico results proposed that these newly synthesized compounds might be used as anticoagulant agents.

合成了一系列新的 1,3,4-噁二唑衍生物，并对其进行了表征和体外及体内抗血栓活性评价。与参比药物链激酶（30000IU）相比，化合物（⁻）显示出显著的血凝块溶解作用，与肝素（110s）相比，其凝固时间（CT）值（130-342s）延长。与对照配体 RPR200095 相比，化合物（、、、、和）对 1NFY 的亲和力更高，对接评分也更高。此外，与对照配体 RPR200095 相比（对接评分 5192；ACE-197.81kcal/mol），这些化合物对因子 Xa（F-Xa）表现出显著的抑制作用，对接评分更高（5612-6270），原子接触能（ACE）值也更高（-189.68 至-352.28kcal/mol）。体外、体内和计算结果表明，这些新合成的化合物可能可用作抗凝剂。