Structure-activity relationship study of peptidomimetic aldehydes as enterovirus 71 3C protease inhibitors.
A series of peptidomimetic aldehydes were designed, synthesized, and evaluated for their biochemical activity against 3C protease (3Cpro) and anti-enterovirus 71 (EV71) activity in vitro. Molecular docking revealed that 5s (IC50= 0.22 ± 0.07 μM, EC50= 0.18 ± 0.05 μM) could bind well to the active site of EV71 3Cpro, which was consistent with the biological data compared to reference 5a (IC50= 0.54 ± 0.02 μM, EC50= 0.26 ± 0.07 μM). Structure and relationship study led to the discovery of aldehyde 5x (IC50= 0.10 ± 0.02 μM, EC50= 0.11 ± 0.07 μM), which exhibited the most potent 3Cproinhibitory and antiviral activity.
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
Yangyang
Y
Zhai
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
Yuying
Y
Ma
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
Fei
F
Ma
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
Quandeng
Q
Nie
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
Xuejiao
X
Ren
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
Yaxin
Y
Wang
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China. Electronic address: shanglq@nankai.edu.cn.
Luqing
L
Shang
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China. Electronic address: zheng_yin@nankai.edu.cn.
Zheng
Z
Yin
D000447:Aldehydes / Q000494:pharmacology*; D029821:Enterovirus A, Human / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D057786:Peptidomimetics / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000447:Aldehydes; D057786:Peptidomimetics; D011480:Protease Inhibitors
Biological activity; Enterovirus 71 (EV71); Peptidomimetic aldehydes; Structure–activity relationship (SAR) study