{"doi":"10.1371/journal.pone.0227224","title":"Intracellular and in vivo evaluation of imidazo[2,1-b]thiazole-5-carboxamide anti-tuberculosis compounds","abstract":"The imidazo[2,1-b]thiazole-5-carboxamides (ITAs) are a promising class of anti-tuberculosis agents shown to have potent activity in vitro and to target QcrB, a key component of the mycobacterial cytochrome bcc-aa3 super complex critical for the electron transport chain. Herein we report the intracellular macrophage potency of nine diverse ITA analogs with MIC values ranging from 0.0625-2.5 μM and mono-drug resistant potency ranging from 0.0017 to 7 μM. The in vitro ADME properties (protein binding, CaCo-2, human microsomal stability and CYP450 inhibition) were determined for an outstanding compound of the series, ND-11543. ND-11543 was tolerable at >500 mg/kg in mice and at a dose of 200 mg/kg displayed good drug exposure in mice with an AUC(0-24h) >11,700 ng·hr/mL and a >24 hr half-life. Consistent with the phenotype observed with other QcrB inhibitors, compound ND-11543 showed efficacy in a chronic murine TB infection model when dosed at 200 mg/kg for 4 weeks. The efficacy was not dependent upon exposure, as pre-treatment with a known CYP450-inhibitor did not substantially improve efficacy. The ITAs are an interesting scaffold for the development of new anti-TB drugs especially in combination therapy based on their favorable properties and novel mechanism of action.","journal":"PLoS ONE","year":2020,"id":91295,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":457247,"name":"Nathalie Deboosère","orcid":"0000-0002-2873-5485","position":1,"is_corresponding":false},{"id":458140,"name":"Kate Marshall","orcid":null,"position":2,"is_corresponding":false},{"id":458141,"name":"Heath A. Weaver","orcid":null,"position":3,"is_corresponding":false},{"id":457248,"name":"Alexandre Vandeputte","orcid":"0000-0003-2936-2411","position":4,"is_corresponding":false},{"id":458142,"name":"Courtney Hastings","orcid":null,"position":5,"is_corresponding":false},{"id":458143,"name":"Lisa K. Woolhiser","orcid":null,"position":6,"is_corresponding":false},{"id":458144,"name":"Anne J. Lenaerts","orcid":null,"position":7,"is_corresponding":false},{"id":457249,"name":"Priscille Brodin","orcid":"0000-0003-0991-7344","position":8,"is_corresponding":false},{"id":283179,"name":"Marvin J. Miller","orcid":"0000-0002-3704-8214","position":9,"is_corresponding":false},{"id":283183,"name":"Garrett C. Moraski","orcid":"0000-0002-6992-5584","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T22:28:45.409789Z","pmid":"31905374","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}