@article{Njoroge2019,
abstract = {Fusidic acid (FA), a natural product fusidane triterpene-based antibiotic with unique structural features, is active in vitro against Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). While possessing good pharmacokinetics in man, FA is rapidly metabolized in rodents – thus complicating proof-of-concept studies in this model. Towards the repositioning of FA as an anti-TB agent, we herein describe the synthesis, activity and metabolism of FA and semi-synthesized ester derivatives in rat liver microsomes, rat plasma and mycobacterial cell culture. FA and derivative molecules with a free C-3 OH underwent species-specific metabolism to the corresponding 3-OH epimer, 3-epifusidic acid (3-epiFA). FA was also metabolized in rat plasma to form FA lactone. These additional routes of metabolism may contribute to the more rapid clearance of FA observed in rodents. C-3 alkyl and aryl esters functioned as classic prodrugs of FA, being hydrolyzed to FA in microsomes, plasma and Mycobacterium tubercu...},
author = {Njoroge, Mathew and Kaur, Gurminder and Espinoza-Moraga, Marlene and Wasuna, Antonina and Dziwornu, Godwin Akpeko and Seldon, Ronnett and Taylor, Dale and Okombo, John and Warner, Digby F and Chibale, Kelly},
doi = {10.1021/acsinfecdis.9b00208},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Njoroge et al. - 2019 - Semisynthetic antimycobacterial C-3 silicate and C-3C-21 ester derivatives of fusidic acid pharmacological evalu.pdf:pdf},
journal = {ACS Infectious Diseases},
keywords = {fund{\_}not{\_}ack,original},
mendeley-tags = {fund{\_}not{\_}ack,original},
month = {jul},
number = {9},
pages = {1634--1644},
publisher = {American Chemical Society},
title = {{Semisynthetic antimycobacterial C-3 silicate and C-3/C-21 ester derivatives of fusidic acid: pharmacological evaluation and stability studies in liver microsomes, rat plasma and Mycobacterium tuberculosis culture}},
url = {http://pubs.acs.org/doi/10.1021/acsinfecdis.9b00208},
volume = {5},
year = {2019}
}

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Towards the repositioning of FA as an anti-TB agent, we herein describe the synthesis, activity and metabolism of FA and semi-synthesized ester derivatives in rat liver microsomes, rat plasma and mycobacterial cell culture. FA and derivative molecules with a free C-3 OH underwent species-specific metabolism to the corresponding 3-OH epimer, 3-epifusidic acid (3-epiFA). FA was also metabolized in rat plasma to form FA lactone. These additional routes of metabolism may contribute to the more rapid clearance of FA observed in rodents. 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