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Synthesis and Evaluation of a Series of New Bulleyaconitine A Derivatives as Analgesics.

ABSTRACT: As a nonaddictive analgesic widely used in clinics, the LD50 of bulleyaconitine A is just only 0.92 mg/kg, which exhibits obvious toxicity. Therefore, 31 new non-natural C19-diterpenoid alkaloids (2a-w, 2'a-e, 3, 4a, and 4b) were designed and synthesized from bulleyaconitine A to develop nonaddictive analgesics with low toxicity. The chemical structures were characterized by 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS) spectra. The analgesic activities were evaluated by a hot plate test in mice. At the dosage of 10 mg/kg, six compounds (2d, 2j, 2k, 2m, 2t, 2w) exhibited good analgesic activities (increased pain threshold >100%) with a long duration. Among them, 2w showed the best analgesic activity and the longest duration. Its pain threshold reached 166.35% in 15 min, peaked at 30 min (182.35%), and remained 82.59% even at 60 min.

SUBMITTER: Zhang X

PROVIDER: S-EPMC7450621 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Synthesis and Evaluation of a Series of New Bulleyaconitine A Derivatives as Analgesics.

Zhang Xing X Shang Yu-Shan YS Gao Feng F Fang Dong-Mei DM Li Xiao-Huan XH Zhou Xian-Li XL

ACS omega 20200817 33

As a nonaddictive analgesic widely used in clinics, the LD50 of bulleyaconitine A is just only 0.92 mg/kg, which exhibits obvious toxicity. Therefore, 31 new non-natural C19-diterpenoid alkaloids (2a-w, 2'a-e, 3, 4a, and 4b) were designed and synthesized from bulleyaconitine A to develop nonaddictive analgesics with low toxicity. The chemical structures were characterized by 1H NMR, 13C NMR, and high-res ...[more]

PMID: 32875257

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