An arylsulphonamide that targets cell wall biosynthesis in Mycobacterium tuberculosis
Allen, R.; Ames, L.; Baldin, V. P.; Butts, A.; Henry, K. J.; Quach, D.; Sugie, J.; Pogliano, J.; Parish, T.
Show abstract
We investigated the mechanism of action of an arylsulphonamide with whole cell activity against Mycobacterium tuberculosis. We newly synthesized the molecule and confirmed it had activity against both extracellular and intracellular bacilli. The molecule had some activity against HepG2 cells but maintained some selectivity. Bacterial cytological profiling suggested that mechanism of action was via disruption of cell wall synthesis, with similarities to an inhibitor of the mycolic acid exporter MmpL3. The compound induced expression from the IniB promoter and caused a boost in ATP production but did not induce reactive oxygen species. A mutation in MmpL3 (S591I) led to low-level resistance. Taken together these data confirm the molecule targets cell wall biosynthesis with MmpL3 as the most probable target.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Broad-Spectrum Activity and Mechanisms of Action of SQ109 on a Variety of Fungi 93%
- High-throughput screening of more than 30,000 compounds for anthelmintics against gastrointestinal nematode parasites 92%
- Antibiotic-adjuvants abolish resistance conferred by the Staphylococcus aureus erythromycin resistance methyltransferase in an Escherichia coli model 92%
Similar papers in this journal
- Amikacin potentiator activity of zinc complexed to a pyrithione derivative with enhanced solubility 94%
- Identification of kinase inhibitors as potential host-directed therapies for intracellular bacteria 92%
- PKIS Deep Dive Yields a Chemical Starting Point for Dark Kinases and a Cell Active BRSK2 Inhibitor 91%
Similar papers in this journal
- Identification of Leucinostatins from Ophiocordyceps sp. as Antiparasitic Agents Against Trypanosoma cruzi 93%
- Machine learning approaches identify chemical features for stage-specific antimalarial compounds 92%
- Chalcogen derivatives for the treatment of African trypanosomiasis: biological evaluation of thio and seleno- semicarbazones and their azole derivatives 91%
Similar papers in this journal
- Discovery of inhibitors for bacterial Arr enzymes ADP-ribosylating and inactivating rifamycin antibiotics 93%
- Selectivity of the time-dependent M. tuberculosis LeuRS inhibitor ganfeborole is driven by target vulnerability 93%
- Inhibition of Mycobacterium tuberculosis DosRST two-component regulatory system signaling by targeting response regulator DNA binding and sensor kinase heme 92%
Similar papers in this journal
- Identification of new MmpL3 inhibitors by untargeted and targeted mutant screens defines MmpL3 domains with differential resistance 94%
- GSK2556286 is a novel antitubercular drug candidate effective in vivo with the potential to shorten tuberculosis treatment 94%
- A novel oral GyrB/ParE dual binding inhibitor effective against multidrug resistant Neisseria gonorrhoeae and other high-threat pathogens 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.