Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents

In the current work, in continuation of our recent research, we synthesized and studied new chimeric compounds, including ribosome-targeting antibiotic chloramphenicol (CHL) membrane-penetrating cation triphenylphosphonium (TPP), which are linked by alkyl groups different lengths. Using various biochemical assays, showed that these CAM-Cn-TPP compounds bind to bacterial ribosome, inhibit protein synthesis vitro vivo a way similar parent CHL, significantly reduce membrane potential. Similar CAM-C4-TPP, mode action CAM-C10-TPP CAM-C14-TPP ribosomes differs from CHL. By simulating dynamics complexes with ribosomes, proposed possible explanation for specificity analogs translation process. more strongly growth Gram-positive bacteria, as compared suppress some CHL-resistant strains. Thus, have shown TPP derivatives CHL dual-acting targeting both cellular membranes bacteria. The fragment has an inhibitory effect on Moreover, since mitochondria eukaryotic cells possess qualities those their prokaryotic ancestors, demonstrate possibility chemoresistant cancer compounds.