Structural Optimization and Structure–Activity Relationship of 4-Thiazolidinone Derivatives as Novel Inhibitors of Human Dihydroorotate Dehydrogenase
Fanxun Zeng,
Lina Quan,
Guantian Yang,
Tiantian Qi,
Letian Zhang,
Shiliang Li,
Honglin Li,
Lili Zhu,
Xiaoyong Xu
Affiliations
Fanxun Zeng
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China
Lina Quan
Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China
Guantian Yang
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China
Tiantian Qi
Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China
Letian Zhang
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China
Shiliang Li
Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China
Honglin Li
Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China
Lili Zhu
Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China
Xiaoyong Xu
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China
Human dihydroorotate dehydrogenase (hDHODH), one of the attractive targets for the development of immunosuppressive drugs, is also a potential target of anticancer drugs and anti-leukemic drugs. The development of promising hDHODH inhibitors is in high demand. Based on the unique binding mode of our previous reported 4-thiazolidinone derivatives, via molecular docking method, three new series 4-thiazolidinone derivatives were designed and synthesized as hDHODH inhibitors. The preliminary structure−activity relationship was investigated. Compound 9 of biphenyl series and compound 37 of amide series displayed IC50 values of 1.32 μM and 1.45 μM, respectively. This research will provide valuable reference for the research of new structures of hDHODH inhibitors.
