In Vitro Efficacies, ADME, and Pharmacokinetic Properties of Phenoxazine Derivatives Active against Mycobacterium tuberculosis.

Autor:	Tanner L; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa tnnllo001@myuct.ac.za., Evans JC; SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Seldon R; SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; H3D Drug Discovery and Development Centre, Department of Chemistry, University of Cape Town, Cape Town, South Africa., Jordaan A; SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Warner DF; SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa., Haynes RK; Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa., Parkinson CJ; School of Biomedical Sciences, Charles Sturt University, Orange, New South Wales, Australia., Wiesner L; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2019 Oct 22; Vol. 63 (11). Date of Electronic Publication: 2019 Oct 22 (Print Publication: 2019).
DOI:	10.1128/AAC.01010-19
Abstrakt:	Mycobacterium tuberculosis , the causative agent of tuberculosis, remains a leading infectious killer globally, demanding the urgent development of faster-acting drugs with novel mechanisms of action. Riminophenazines such as clofazimine are clinically efficacious against both drug-susceptible and drug-resistant strains of M. tuberculosis We determined the in vitro anti- M. tuberculosis activities, absorption, distribution, metabolism, and excretion properties, and in vivo mouse pharmacokinetics of a series of structurally related phenoxazines. One of these, PhX1, displayed promising drug-like properties and potent in vitro efficacy, supporting its further investigation in an M. tuberculosis -infected animal model. (Copyright © 2019 American Society for Microbiology.)
Databáze:	MEDLINE
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