Asset Details
Do you wish to reserve the book?
Pentacyclic Nitrofurans with In Vivo Efficacy and Activity against Nonreplicating Mycobacterium tuberculosis
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Pentacyclic Nitrofurans with In Vivo Efficacy and Activity against Nonreplicating Mycobacterium tuberculosis
Do you wish to request the book?
Pentacyclic Nitrofurans with In Vivo Efficacy and Activity against Nonreplicating Mycobacterium tuberculosis
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Pentacyclic Nitrofurans with In Vivo Efficacy and Activity against Nonreplicating Mycobacterium tuberculosis
2014
Overview
The reductively activated nitroaromatic class of antimicrobials, which include nitroimidazole and the more metabolically labile nitrofuran antitubercular agents, have demonstrated some potential for development as therapeutics against dormant TB bacilli. In previous studies, the pharmacokinetic properties of nitrofuranyl isoxazolines were improved by incorporation of the outer ring elements of the antitubercular nitroimidazole OPC-67683. This successfully increased stability of the resulting pentacyclic nitrofuran lead compound Lee1106 (referred to herein as 9a). In the current study, we report the synthesis and antimicrobial properties of 9a and panel of 9a analogs, which were developed to increase oral bioavailability. These hybrid nitrofurans remained potent inhibitors of Mycobacterium tuberculosis with favorable selectivity indices (>150) and a narrow spectrum of activity. In vivo, the pentacyclic nitrofuran compounds showed long half-lives and high volumes of distribution. Based on pharmacokinetic testing and lack of toxicity in vivo, 9a remained the series lead. 9a exerted a lengthy post antibiotic effect and was highly active against nonreplicating M. tuberculosis grown under hypoxia. 9a showed a low potential for cross resistance to current antitubercular agents, and a mechanism of activation distinct from pre-clinical tuberculosis candidates PA-824 and OPC-67683. Together these studies show that 9a is a nanomolar inhibitor of actively growing as well as nonreplicating M. tuberculosis.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Antitubercular Agents - chemical synthesis
/ Antitubercular Agents - chemistry
/ Antitubercular Agents - pharmacokinetics
/ Antitubercular Agents - pharmacology
/ Bacilli
/ Biology
/ Heterocyclic Compounds, 4 or More Rings - chemical synthesis
/ Heterocyclic Compounds, 4 or More Rings - chemistry
/ Heterocyclic Compounds, 4 or More Rings - pharmacokinetics
/ Heterocyclic Compounds, 4 or More Rings - pharmacology
/ Hypoxia
/ Medicine
/ Mycobacterium tuberculosis - metabolism
/ Nitrofurans - chemical synthesis
/ Nitrofurans - pharmacokinetics
/ Pharmacy
/ Toxicity
