RESUMO
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.
Assuntos
Antibacterianos/síntese química , Eritritol/análogos & derivados , Terpenos/antagonistas & inibidores , Antibacterianos/química , Antibacterianos/farmacologia , Capsicum/efeitos dos fármacos , Eritritol/síntese química , Eritritol/química , Eritritol/farmacologia , Escherichia coli/efeitos dos fármacos , Ésteres , Éteres/síntese química , Éteres/química , Éteres/farmacologia , Mycobacterium smegmatis/efeitos dos fármacos , Relação Estrutura-Atividade , Terpenos/metabolismoRESUMO
To work out a test system for studying the inhibition of isoprenoid biosynthesis through non-mevalonate pathway, the conversion of 2-(14)C-methylerythritol 2,4-cyclodiphosphate (14C-MEC) into isoprenoids of three bacteria species and into plastids of 11 higher plant species was studied. The highest efficiency (up to 63%) of the process was observed with chromoplasts from narcissus (Narcissus pseudonarcissus L.) and celandine (Chelidonium majus L.). Twenty five percent of added 14C-MEC was recovered in an isoprenoid fraction of red pepper (Capsicum annuum L.) chromoplasts. Thus, these three models can be used to test antibiotic inhibitors of isoprenoid biosynthesis.