Synthesis and antituberculosis activity of novel mefloquine-isoxazole carboxylic esters as prodrugs

Add time:08/30/2019    Source:sciencedirect.com

5-(2,8-Bis(trifluoromethyl)quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester (compound 3) was reported to have excellent antituberculosis activity against both replicating and non-replicating Mycobacterium tuberculosis, with a minimum inhibitory concentration (MIC) of 0.9 μM and 12.2 μM, respectively. In this study, the antituberculosis activity of compound 3 was further investigated. Its activity appeared to be very specific for organisms of the M. tuberculosis complex and it effected significant reductions of bacterial numbers in infected macrophages with an EC90 of 4.1 μM. More importantly, the increased in vitro antituberculosis activity of the corresponding acid (compound 4) at pH 6.0 suggested that it may be active in vivo in an acidic environment produced as a consequence of inflammation in the lungs of TB patients. The fact that various ester bioisosteres of compound 3 lost anti-TB activity further suggested that the ester compound 3 may function as a prodrug. The detailed structure–activity relationships (SARs) from this study should facilitate our ultimate goal of improving the anti-TB potency of this isoxazole ester series.

We also recommend Trading Suppliers and Manufacturers of 4-METHYL-PIPERAZINE-1-CARBOXYLIC ACID PHENYL ESTER (cas 132906-06-0). Pls Click Website Link as below: cas 132906-06-0 suppliers

Prev:Nanoparticulate delivery of irinotecan active metabolite (SN38) in murine colorectal carcinoma through conjugation to poly (2-ethyl 2-oxazoline)-b-poly (L-glutamic acid) double hydrophilic copolymer
Next:Influence of microheterogeneity on the solution phase photophysics of a newly synthesised, environment sensitive fluorophore 2-((7,8-dimethyl-1-oxo-2,3,4,9-tetrahydro-1H-carbazol-6-yl)oxy)acetic acid and its tagged derivative)