Simple dihydrosphyngosine analogues with potent activity against MDR-Mycobacterium tuberculosis

Fifteen dihydrosphingosine analogues have been synthesized and tested in vitro against Mycobacterium tuberculosis (MTB). Two ether (3 and 4b) and one diamine (8b) derivatives have displayed high mycobactericidal potency, with similar MIC values of 1.25 μg/mL, against the virulent strain H37Rv, as well as against a clinical isolate resistant to the five first-line anti-TB drugs. The three compounds, tested on other eleven cultured MTB strains with different multi-drug-resistance (MDR) patterns, retained their MIC values for most strains, or even lowered it, as in the case of compound 4b, which, assayed on strain No. 332, also resistant to all first-line anti-TB drugs, attained the MIC value of 0.78 μg/mL.

Graphical abstractA number of dihydrosphingosine analogues were tested in vitro against several strains of Mycobacterium tuberculosis (MTB). Three (3, 4b and 8b) out of the fifteen evaluated compounds, displayed MIC values of 1.25 μg/mL on virulent H37Rv and several MDR strains and, more interestingly, on one clinical isolate resistant to all the first-line anti-TB drugs.Figure optionsDownload full-size imageDownload as PowerPoint slide