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Biological evaluation of OSM-S-117 through 138 (also OSM-S-107) performed in Vicky Avery's lab by Sabine Fletcher.
Data for previous OSM-S compounds can be found here - OSM Compound List
Unfortunately only two (OSM-S- 137 and 138) were active on 3D7.
The summary also contains information about the solubility: several of the compounds turned opaque when diluted down to 4% DMSO, which suggests poor solubility in this condition. I made sure to mix the compounds very well before the final 1:10 dilution step in the assay plate.
One compound (OSM-S-134) did not dissolve well in 100% DMSO. It still contained many needle-like crystals after shaking over night, which means that we do not know the actual concentration of the dissolved compound in the assay. As tested here, it was completely inactive.
Click for larger image
Click for larger image
Depictions of Data including cLogP values and comments on solubility:
Activities of hit vs simple analogs
Variation of amine to morpholine
Variation in amine component
Comparison with known other TCMDC hits
Biological evaluation of OSM-S-106 through 116 (excluding OSM-S-107) performed in Vicky Avery's lab by Sabine Fletcher.
The compounds look good in this round - all but cpd OSM-S-113 show activity.
I already ran the cytotoxicity as well, and none of the compounds was particularly cytotoxic (see 'summary report' file and curves in PDF).
Solubility: minor floating specks after dissolving in OSM-S-106; all others fine
Unfortunately I made a minor mistake: I started the Artemisinin CRC curve at the wrong concentration, 40 uM (same concentration as the compounds) as opposed to the usual 2 uM. The IC50 value obtained for the control is correct (4 nM), just the x-axis range of the curve is different compared to the previous runs. Sorry for that!
Displacement Curves
Strings
| ID | InChI | 3D7 IC50 (nM) |
| OSM-S-106 | InChI=1S/C12H10N4O2S2/c13-12-11-9(15-6-16-12)5-10(19-11)7-2-1-3-8(4-7)20(14,17)18/h1-6H,(H2,13,15,16)(H2,14,17,18) | 36 |
| OSM-S-108 | InChI=1S/C16H15N3OS/c1-10-8-12(11(2)17-10)9-14-15(20)19-16(21-14)18-13-6-4-3-5-7-13/h3-9,17H,1-2H3,(H,18,19,20)/b14-9- | 1200 |
| OSM-S-109 | InChI=1S/C22H18N4O3S/c1-14-12-16(15(2)25(14)18-8-10-19(11-9-18)26(28)29)13-20-21(27)24-22(30-20)23-17-6-4-3-5-7-17/h3-13H,1-2H3,(H,23,24,27)/b20-13- | 262 |
| OSM-S-110 | InChI=1S/C22H18N4O4S/c1-13-10-15(14(2)25(13)17-6-8-18(9-7-17)26(29)30)11-20-21(28)24-22(31-20)23-16-4-3-5-19(27)12-16/h3-12,27H,1-2H3,(H,23,24,28)/b20-11- | 2300 |
| OSM-S-111 | InChI=1S/C23H21N3O2S/c1-15-13-17(16(2)26(15)19-9-11-20(28-3)12-10-19)14-21-22(27)25-23(29-21)24-18-7-5-4-6-8-18/h4-14H,1-3H3,(H,24,25,27)/b21-14- | 146 |
| OSM-S-112 |
InChI=1S/C23H21N3O3S/c1-14-11-16(15(2)26(14)18-7-9-20(29-3)10-8-18)12-21-22(28)25-23(30-21)24-17-5-4-6-19(27)13-17/h4-13,27H,1-3H3,(H,24,25,28)/b21-12- |
1600 |
| OSM-S-113 | InChI=1S/C21H18N4O2S/c1-13-11-15(14(2)25(13)19-5-3-4-10-22-19)12-18-20(27)24-21(28-18)23-16-6-8-17(26)9-7-16/h3-12,26H,1-2H3,(H,23,24,27)/b18-12- | >40,000 |
| OSM-S-114 |
InChI=1S/C22H19N3O2S/c1-14-11-16(15(2)25(14)18-8-4-3-5-9-18)12-20-21(27)24-22(28-20)23-17-7-6-10-19(26)13-17/h3-13,26H,1-2H3,(H,23,24,27)/b20-12- |
1200 |
| OSM-S-115 |
InChI=1S/C22H19N3O2S/c1-14-12-16(15(2)25(14)18-6-4-3-5-7-18)13-20-21(27)24-22(28-20)23-17-8-10-19(26)11-9-17/h3-13,26H,1-2H3,(H,23,24,27)/b20-13- |
1800 |
| OSM-S-35 | InChI=1S/C22H19N3OS/c1-15-13-17(16(2)25(15)19-11-7-4-8-12-19)14-20-21(26)24-22(27-20)23-18-9-5-3-6-10-18/h3-14H,1-2H3,(H,23,24,26)/b20-14- | 38 |
| OSM-S-116 | InChI=1S/C16H17FN2O3/c1-9-8-14(16(21)22-11(3)15(18)20)10(2)19(9)13-6-4-12(17)5-7-13/h4-8,11H,1-3H3,(H2,18,20) | 11000 |
