Synthesis and antimycobacterial evaluation of natural oridonin and its enmein-type derivatives

Fitoterapia. 2014 Dec:99:300-6. doi: 10.1016/j.fitote.2014.10.005. Epub 2014 Oct 12.

Abstract

A series of enmein-type derivatives were synthesized and assayed for their antimycobacterial effects. The structures of the synthesized compounds were established by (1)H NMR, (13)C NMR and mass spectral analysis. All the compounds were screened for their antimycobacterial properties against Mycobacterium phlei, Mycobacterium smegmatis and Mycobacterium marinum. Compounds 2, 6g and 6i were found to exhibit potent antimycobacterial activity against M. phlei at a concentration of 0.5 μg/mL, which was comparable to that of positive drug streptomycin. Furthermore, five compounds were tested against Mycobacterium tuberculosis H₃₇Rv based on the promising preliminary screening results. Among them, compound 10 showed potent activity with IC₅₀ value of 17.1 μg/mL against M. tuberculosis H₃₇Rv strain. Thus, compound 10 could emerge as a promising lead for further research work.

Keywords: Antimycobacterial activity; Enmein (PubChem CID: 352542); Enmein-type; Lasiokaurin (PubChem CID: 99618); Natural product; Oridonin; Oridonin (PubChem CID: 34378); Tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / pharmacology*
  • Diterpenes / chemical synthesis
  • Diterpenes / pharmacology*
  • Diterpenes, Kaurane / chemical synthesis
  • Diterpenes, Kaurane / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium / drug effects*

Substances

  • Antitubercular Agents
  • Diterpenes
  • Diterpenes, Kaurane
  • oridonin
  • enmein