34490-00-1Relevant articles and documents
Anthranilic amide and imidazobenzothiadiazole compounds disrupt: Mycobacterium tuberculosis membrane potential
Smith, Jake,Wescott, Heather,Early, Julie,Mullen, Steven,Guzman, Junitta,Odingo, Joshua,Lamar, Jason,Parish, Tanya
, p. 934 - 945 (2019/06/27)
A family of compounds typified by an anthranilic amide 1 was identified from a whole-cell screening effort targeted at identifying compounds that disrupt pH homeostasis in Mycobacterium tuberculosis. 1 demonstrated bactericidal activity against non-replicating M. tuberculosis in pH 4.5 buffer (MBC4.5 = 6.3 μM). Exploration of the structure-activity relations failed to simplify the scaffold. The antitubercular activity proved dependent on the lipophilicity and planarity of the molecule and directly correlated with mammalian cytotoxicity. Further studies revealed a pH-dependent correlation between the family's disruption of M. tuberculosis membrane potential and antitubercular activity, with active compounds causing a drop in membrane potential at concentrations below their MBC4.5. A second compound family, identified in the same screening effort and typified by imidazo(4,5-e)(2,1,3)benzothiadiazole 2, provided a contrasting profile. As with 1, structure-activity profiling of 2 (MBC4.5 = 25 μM) failed to minimize the initial scaffold, mammalian cytotoxicity was observed for a majority of the active compounds, and many of the active compounds disrupted M. tuberculosis membrane potential. However, unlike the anthranilic amide compounds, the benzothiadiazole compounds disrupted M. tuberculosis membrane potential primarily at concentrations above the MBC4.5 in a pH-independent fashion. These differences suggest an alternative mechanism of action for the benzothiadiazole compounds. As a result, while the cytotoxicity of the anthranilic amides limits their utility to tool compounds, benzothiadiazole 2 presents an attractive target for more focused SAR exploration.
Synthesis and in vitro study of platelet antiaggregant activity of 1,2,3,4-tetrahydroquinazoline derivatives
Gravier,Dupin,Casadebaig,Hou,Boisseau,Bernard
, p. 531 - 535 (2007/10/02)
Some original 3-substituted 1,2,3,4-tetrahydroquinazolines were synthesized. Their antiplatelet activity was evaluated in vitro with respect to aggregation induced by the main inducers (ADP, collagen, arachidonic acid), platelet serotonin release reaction and thromboxane A2 synthesis. All these molecules possess an inhibiting power which, compared to that of aspirin in the same conditions, is the same or greater when aggregation is induced by ADP.