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4‐Substituted Thioquinolines and Thiazoloquinolines: Potent, Selective, and Tween‐80 in vitro Dependent Families of Antitubercular Agents with Moderate in vivo Activity
Author(s) -
Escribano Jaime,
RiveroHernández Cristina,
Rivera Hilda,
Barros David,
CastroPichel Julia,
PérezHerrán Esther,
MendozaLosana Alfonso,
AnguloBarturen Íñigo,
FerrerBazaga Santiago,
JiménezNavarro Elena,
Ballell Lluís
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100309
Subject(s) - in vivo , resazurin , in vitro , chemistry , pharmacology , biochemistry , biology , microbiology and biotechnology
Two new families of closely related selective, non‐cytotoxic, and potent antitubercular agents were discovered: thioquinolines and thiazoloquinolines. The compounds were found to possess potent antitubercular properties in vitro, an activity that is dependent on experimental conditions of MIC determination (resazurin test and the presence or absence of Tween‐80). To clarify the therapeutic potential of these compound families, a medicinal chemistry effort was undertaken to generate a lead‐like structure that would enable murine efficacy studies and help elucidate the in vivo implications of the in vitro observations. Although the final compounds showed only limited levels of systemic exposure in mice, modest levels of efficacy in vivo at nontoxic doses were observed.