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 microg/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 microg/mL.
Del Olmo
Esther
E
Departamento de Química Farmacéutica, Facultad de Farmacia, CIETUS, Universidad de Salamanca, Spain. olmo@usal.es
Molina-Salinas
Gloria María
GM
Escarcena
Ricardo
R
Alves
Mario
M
López-Pérez
José L
JL
Hernandez-Pando
Rogelio
R
Said-Fernández
Salvador
S
Feliciano
Arturo San
AS
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
D000900:Anti-Bacterial Agents; D013110:Sphingosine; C005682:safingol