Mechanism of Action of CM-55, a Synthetic Analogue of the Antilipogenic Antibiotic Cerulenin

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RESUMO

CM-55 is a synthetic analogue of the antibiotic cerulenin with the chemical structure of 2, 3-dodecenyl-4-oxo-dimethyl amide. This compound inhibited the growth of Saccharomyces cerevisiae ATCC 12341 and inhibited protein and lipid synthesis by 91 and 95%, respectively, at a concentration of 50 μg/ml (2.1 × 10−4 M). The inhibition of protein synthesis was associated with the partial reduction of ribonucleic acid synthesis and leucine transport. The mechanism of inhibition of lipid synthesis was further investigated in a cell-free extract of the yeast. CM-55 inhibited the incorporation of [14C]acetyl Coenzyme A (CoA) into both fatty acid (FAF) and non-saponifiable fractions (NSF). However, it did not inhibit [14C]malonyl CoA incorporation into FAF and only slightly inhibited [14C]mevalonate incorporation into NSF. The activity of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) synthase was inhibited more strongly than the incorporation of [14C]3-hydroxy-3-methylglutaryl CoA into NSF; this could account for the CM-55 inhibition of [14C]acetyl CoA incorporation into NSF.

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