Phenoxyalkylimidazoles with an oxadiazole moiety are subject to efflux in Mycobacterium tuberculosis

• Published in: PloS one Vol. 16; no. 1; p. e0239353
• Main Authors: Thayer, Mai B., Parish, Tanya
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.01.2021; Public Library of Science (PLoS)
• Subjects: Albumins; Antitubercular Agents - pharmacology; Bacterial Proteins - drug effects; Biology and Life Sciences; Carbonyl Cyanide m-Chlorophenyl Hydrazone - metabolism; Carbonyl Cyanide m-Chlorophenyl Hydrazone - pharmacology; Care and treatment; Catalase; Control; Cytochrome; Dextrose; Drug metabolism; Drugs; Efflux; Experiments; Global health; Humans; Imidazole; Infectious diseases; Isoniazid - chemistry; Isoniazid - pharmacology; Medicine and Health Sciences; Membrane Transport Proteins - drug effects; Metabolism; Microbial Sensitivity Tests - methods; Molecular structure; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Oleic acid; Oxadiazoles; Oxadiazoles - chemistry; Oxadiazoles - pharmacology; Oxazole; Pharmacokinetics; Pharmacology, Experimental; Phenols - chemistry; Phenols - pharmacology; Physical Sciences; Properties; Public health; Reserpine; Reserpine - metabolism; Reserpine - pharmacology; Structure-activity relationship (Pharmacology); Structure-activity relationships; Testing; Tuberculosis; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0239353

The phenoxyalkylimidazoles (PAI) are an attractive chemical series with potent anti-tubercular activity targeting Mycobacterium tuberculosis respiration. Our aim was to determine if the PAI compounds are subject to efflux. Two analogs containing an oxadiazole had improved potency in the presence of the efflux inhibitors reserpine and carbonyl cyanide m-chlorophenylhydrazine, whereas the potency of analogs with a diazole was not affected.