Optimization of nitrofuranyl calanolides for the fluorescent detection of Mycobacterium tuberculosis

Tuberculosis is a chronic lethal infectious disease caused by a single pathogen, Mycobacterium tuberculosis (Mtb). Previous studies developed nitrofuranyl calanolide (NFC) compounds as new class of Mtb diagnostic reagent, such as NFC-Tre-5. Through structure-fluorescence relationships (SFR) investigation, in this article, a new fluorescent probe, 3-vinylcoumarin (17a) with a 20-fold increase in the fluorescent fold change (FFC) value, was gained. Taking the advantage of specific trehalose metabolic mechanism of Mtb, 17a was further cooperated with a trehalose motif through modification of 4-propyl group to obtain 17a-Tre. The 17a-Tre could label the live infected mycobacteria in signal murine macrophage such as M. smeg, specifically mark the living Mtb in single cell from other typical species of bacteria, and detect the Mtb cells under microscope from the sputum of patients.