Biological Evaluation of Compounds

Four OSM Series 1 compounds were evaluated in a P. falciparum dual gamete formation assay, with data in the attached report. Literature on this assay is in this paper. The assay was performed by the original Imperial team. 

All compounds were found to be inactive (low activity) against both male and female gametocytes, though the levels of activity for some compounds were higher vs. female than any antimalarials originally tested in the above-linked paper (where the maximum % inhibition at this concentration was 27%).

These data are a little surprising given that several of these compounds had previously displayed very high levels of activity in a late stage gametocyte assay:

Late stage gametocyte testing of a sample set of GSK-Arylpyrrole Series

Late Stage Gametocyte Assay (OSM-S-111)

it might have been expected that there would have been more activity vs (the more susceptible) males.

Compounds tested:

OSM-S-5

CC(N1C2=CC=C(F)C=C2)=C(C(OCC(N)=O)=O)C=C1C InChI=1S/C15H15FN2O3/c1-9-7-13(15(20)21-8-14(17)19)10(2)18(9)12-5-3-11(16)4-6-12/h3-7H,8H2,1-2H3,(H2,17,19) YSUCFIZUNLQZDX-UHFFFAOYSA-N

OSM-S-38

CC1=CC(/C=C(C(N/2)=O)\SC2=N/C3=CC=CC=C3)=C(C)N1C(C=C4)=CC=C4C(F)(F)F InChI=1S/C23H18F3N3OS/c1-14-12-16(15(2)29(14)19-10-8-17(9-11-19)23(24,25)26)13-20-21(30)28-22(31-20)27-18-6-4-3-5-7-18/h3-13H,1-2H3,(H,27,28,30)/b20-13- YBBWTVGRVHTTDD-MOSHPQCFSA-N

OSM-S-39

CC1=CC(/C=C(C(N/2)=O)\SC2=N/C3=CC=CC=C3)=C(C)N1C4=CC(C(F)(F)F)=CC(C(F)(F)F)=C4 InChI=1S/C24H17F6N3OS/c1-13-8-15(9-20-21(34)32-22(35-20)31-18-6-4-3-5-7-18)14(2)33(13)19-11-16(23(25,26)27)10-17(12-19)24(28,29)30/h3-12H,1-2H3,(H,31,32,34)/b20-9- GVGNOLWIUGQIHW-UKWGHVSLSA-N

OSM-S-111

CC1=CC(/C=C(C(N/2)=O)\SC2=N/C3=CC=CC=C3)=C(C)N1C4=CC=C(OC)C=C4 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- KXIVXNPEYYNDHE-STZFKDTASA-N

This post originally authored by Mat Todd