Design, Synthesis, and Biological Evaluation of New Territrem B Analogues

Authors

  • Xiangrui Jiang,

    1. Department of Traditional Chinese Medicine and Natural Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, P. R. China (phone: +86-571-87217313; fax: +86-571-85270026)
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  • Lei Ao,

    1. Department of Traditional Chinese Medicine and Natural Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, P. R. China (phone: +86-571-87217313; fax: +86-571-85270026)
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  • Changxin Zhou,

    1. Department of Traditional Chinese Medicine and Natural Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, P. R. China (phone: +86-571-87217313; fax: +86-571-85270026)
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  • Leixiang Yang,

    1. Department of Traditional Chinese Medicine and Natural Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, P. R. China (phone: +86-571-87217313; fax: +86-571-85270026)
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  • Qijun Zhang,

    1. Department of Traditional Chinese Medicine and Natural Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, P. R. China (phone: +86-571-87217313; fax: +86-571-85270026)
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  • Haibo Li,

    1. Department of Traditional Chinese Medicine and Natural Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, P. R. China (phone: +86-571-87217313; fax: +86-571-85270026)
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  • Lianli Sun,

    1. Department of Traditional Chinese Medicine and Natural Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, P. R. China (phone: +86-571-87217313; fax: +86-571-85270026)
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  • Xiumei Wu,

    1. Zhejiang Hisun Naturelite Pharmaceutical R&D Co., Ltd., 19-G Huazhe Plaza, Hangzhou 310006, P. R. China
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  • Hua Bai,

    1. Zhejiang Hisun Naturelite Pharmaceutical R&D Co., Ltd., 19-G Huazhe Plaza, Hangzhou 310006, P. R. China
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  • Yu Zhao

    1. Department of Traditional Chinese Medicine and Natural Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, P. R. China (phone: +86-571-87217313; fax: +86-571-85270026)
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Abstract

Some 23 analogues of the potent acetylcholinesterase (AChE) inhibitor territrem B (1) were designed, synthesized, and tested for their biological activities. Some of the new synthetic derivatives exhibited IC50 values for AChE inhibition in the upper micromolar range. Molecular-modeling studies indicated that a planar conformation seems to be crucial for AChE inhibition. The two N-atoms of the piperazine moieties in 5o, 5p, and 5r might further enhance the inhibitory effects. The cytotoxicities of selected compounds against six human tumor cell lines were also determined.

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