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

SUBMITTER: Zhang X 

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

REPOSITORIES: biostudies-literature