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Assay Development for High-Throughput Drug Screening Against Mycobacteria
Published on: October 25, 2024
Simple dihydrosphyngosine analogues with potent activity against MDR-Mycobacterium tuberculosis
Esther Del Olmo1, Gloria María Molina-Salinas, Ricardo Escarcena
1Departamento de Química Farmacéutica, Facultad de Farmacia, CIETUS, Universidad de Salamanca, Spain. olmo@usal.es
Abstract:
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.
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