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The selectivity index values were found to be >25, indicating compounds likeliness in drug development for tuberculosis.
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HEK293T cells were seeded on 12-well plates, allowed to recover overnight and treated for the indicated times with the indicated compounds.
The indicated compounds in different concentrations (100 μl) were added to cells.
IC50 values indicated compounds 1 3 exhibited moderate or less cytotoxic activity in vitro.
Areas in which the growth is inhibited indicate compounds or samples with antimicrobial activity.
Besides that the tail-flick tests indicate compounds 7 and 10 as the most actives.
For treatment experiments, NSCs were treated with 0.1% DMSO, indicated compounds (10 μM), and puromycin (positive control) (10 μM).
Out of those, log P is a very common measure of lipophilicity, but C_ratio can also indicate compounds' lipophilicities, since higher carbon ratios indicate fewer polar heteroatoms.
Large ASA- indicates compounds with many electronegative atoms, a parameter similar to polar surface area that is known to have a negative effect in membrane penetration [42,43].
Radioligand binding assays indicated compounds 6f, 6b, and 9f display potent in vitro binding affinities with nanomolar Ki values and at least 100 2000-fold selectivity for CB2.
Kinetic and molecular modeling studies also indicated compounds were mixed-type inhibitors, binding simultaneously to active, peripheral and mid-gorge sites of AChE.
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