Design, Synthesis, and Biological Evaluation of Novel Dual Inhibitors of Secretory Phospholipase A2 and Sphingomyelin Synthase
Xing Gao
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China
Search for more papers by this authorHaojun Gong
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China
Search for more papers by this authorPeng Men
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China
Search for more papers by this authorCorresponding Author
Lu Zhou
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China, Tel.: 0086-021-51980117; Fax: 0086-021-51980125Search for more papers by this authorCorresponding Author
Deyong Ye
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China, Tel.: 0086-021-51980117; Fax: 0086-021-51980125Search for more papers by this authorXing Gao
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China
Search for more papers by this authorHaojun Gong
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China
Search for more papers by this authorPeng Men
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China
Search for more papers by this authorCorresponding Author
Lu Zhou
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China, Tel.: 0086-021-51980117; Fax: 0086-021-51980125Search for more papers by this authorCorresponding Author
Deyong Ye
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China, Tel.: 0086-021-51980117; Fax: 0086-021-51980125Search for more papers by this authorAbstract
A novel series of eight SMS and sPLA2 dual inhibitors containing indole and α-amino cyanide fragments of different length and substitution position was synthesized and evaluated by three different in vitro assays. Biological evaluation showed that all compounds provided inhibitory effects against SMS (about 50% inhibition at 100 µmol/L) and sPLA2 (14–32 µmol/L). All the compounds had the SMS activity better than the positive control compound D609 in SMS2 homogenate, with compounds 5b and 5e ideal for liver homogenate and SMS2 high expression cell homogenate, respectively.
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