[Screening of potential antibiotics, inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis--2-C-methyl-D-erythritol-2,4-cyclodiphosphate derivatives]

Antibiot Khimioter. 2010;55(5-6):3-7.
[Article in Russian]

Abstract

The recently discovered nonmevalonate pathway of isoprenoid biosynthesis is a prospective target in screening of new antibiotics. Because of the absence of the pathway in the animal cells, the specific inhibitors of the pathway will be a new class of antibiotics against many pathogens (which cause, e.g., malaria, tuberculosis, etc), combining high efficiency and low toxicity. Several derivatives of 2-C-methyl-D-erythritol-2,4-cyclodiphosphate (MEC) were synthesized. 4-Phospho-methyl-D-erythritol-1,2-cyclophosphate, benzyl ether and benzyliden derivative of MEC inhibited the 14C-MEC incorporation into isoprenoids of chromoplasts from red pepper with IC50 of 1.7-5 MM. Some inhibition (about 10%) was also observed with the use of dimethyl ether and isopropyliden derivative of MEC.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Capsicum / drug effects
  • Erythritol / analogs & derivatives*
  • Erythritol / chemical synthesis
  • Erythritol / chemistry
  • Erythritol / pharmacology
  • Escherichia coli / drug effects
  • Esters
  • Ethers / chemical synthesis
  • Ethers / chemistry
  • Ethers / pharmacology
  • Mycobacterium smegmatis / drug effects
  • Structure-Activity Relationship
  • Terpenes / antagonists & inhibitors*
  • Terpenes / metabolism

Substances

  • Anti-Bacterial Agents
  • Esters
  • Ethers
  • Terpenes
  • methyl-D-erythritol 2,4-cyclodiphosphate
  • Erythritol