Synthesis and Evaluation of Novel Nitric Oxide-Donating Ligustrazine Derivatives as Potent Antiplatelet Aggregation Agents
Han-Xu Li,
Jian-Hui Tian,
Hua-Yu Li,
Xin Wan,
Yu Zou
Affiliations
Han-Xu Li
Institute of Pharmaceutical Process, Hubei Province Key Laboratory of Occupationl Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
Jian-Hui Tian
Institute of Pharmaceutical Process, Hubei Province Key Laboratory of Occupationl Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
Hua-Yu Li
Institute of Pharmaceutical Process, Hubei Province Key Laboratory of Occupationl Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
Xin Wan
Institute of Pharmaceutical Process, Hubei Province Key Laboratory of Occupationl Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
Yu Zou
Institute of Pharmaceutical Process, Hubei Province Key Laboratory of Occupationl Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
Antiplatelet aggregation agents have demonstrated clinical benefits in the treatment of ischemic stroke. In our study, a series of novel nitric oxide (NO)-donating ligustrazine derivatives were designed and synthesized as antiplatelet aggregation agents. They were evaluated for the inhibitory effect on 5′-diphosphate (ADP)-induced and arachidonic acid (AA)-induced platelet aggregation in vitro. The results showed that compound 15d displayed the best activity in both ADP-induced and AA-induced assays, and compound 14a also showed quite better activity than ligustrazine. The preliminary structure-activity relationships of these novel NO-donating ligustrazine derivatives were discussed. Moreover, these compounds were docked with the thromboxane A2 receptor to study the structure-activity relationships. These results suggested that the novel NO-donating ligustrazine derivatives 14a and 15d deserve further study as potent antiplatelet aggregation agents.
