title: 3,16-Bisquaternary ammonium steroid derivatives as neuromuscular blocking agents: synthesis and biological evaluation.
abstract: Neuromuscular blocking agents (NMBAs) are widely used in surgery to achieve skeleton muscles relaxation under light anesthesia status. In this work, we synthesized a series of 3,16-bisquaternary ammonium steroidal NMBAs. Among them, three compounds exhibited higher in vitro activities than the commenced drug rocuronium. In addition, structure-activity relationship was unveiled. We found that the intact acetylcholine-like moiety in D-ring was not necessary for maintaining activity but both the acetyl group and the quaternary nitrogen were very essential.
authors: State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors: Hao
authors: H
authors: Hu
authors: State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors: Zhigang
authors: Z
authors: Rao
authors: State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors: Min
authors: M
authors: Feng
authors: State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors: Zhe
authors: Z
authors: Wu
authors: Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Jianrong
authors: J
authors: Xu
authors: Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Hongzhuan
authors: H
authors: Chen
authors: State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors: Peng
authors: P
authors: Liu
authors: State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors: Yuling
authors: Y
authors: Xiao
authors: State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors: Xuechuan
authors: X
authors: Hong
authors: State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors: Xianming
authors: X
authors: Hu
authors: Department of Pharmaceutical Engineering, Wuhan Bioengineering Institute, Han-Shi Road 1, Yangluo Economic Development Zone, 430415 Wuhan, China. Electronic address: xianbke@163.com.
authors: Xianbing
authors: X
authors: Ke
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic; D008297:Male; D051379:Mice; D009466:Neuromuscular Blocking Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013256:Steroids / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D009466:Neuromuscular Blocking Agents; D000644:Quaternary Ammonium Compounds; D013256:Steroids
keywords: Muscle relaxant; Neuromuscular blocking agent; nAChR