Screening of Potential Antibiotics, Inhibitors of the Nonmevalonate Pathway of Isoprenoid Biosynthesis (2-C-Methyl-D-Erythritol-2,4-Cyclodiphosphate Derivatives)

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...

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Bibliographic Details
Main Authors: YU. V. Ershov, K. V. Mazikin, D. N. Ostrovsky
Format: Article
Language:Russian
Published: LLC "Publishing House OKI" 2020-05-01
Series:Антибиотики и Химиотерапия
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Online Access:https://www.antibiotics-chemotherapy.ru/jour/article/view/303
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Summary: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 the14C-MEC incorporation into isoprenoids of chromoplasts from red pepper with IC50 of 1.7-5 мМ. Some inhibition (about 10 %) was also observed with the use of dimethyl ether and isopropyliden derivative of MEC.
ISSN:0235-2990