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11th November 2015 @ 01:28

A further set of Series 4 Triazolopyrazine compounds have been sent to have their efficacy evaluated against Plasmodium falciparum in-vitro at Syngene.

Some compounds were synthesised by the SSP group at The University Sydney and then purified in the research lab.

Structures are as follows and data will be published in due course:


General assay principle:

"This protocol assesses compound efficacy against Plasmodium falciparum in-vitro. This assay is using [3H]-hypoxanthine incorporation or DNA labeling by SYBR Green as a markers of parasite growth. 
This procedure is designed for use with culture adapted P. falciparum strains or clones only. On one 96-well plate typically 03 drugs are tested in duplicate. Standard strains: Plasmodium falciparum, NF54 (sensitive to all known drugs), Plasmodium falciparum, K1 (chloroquine and pyrimethamine resistant). The assay can be performed in dose response mode (12 concentrations in duplicate, 24 data points) which allows determining IC50, or in single concentration mode (one concentration in triplicate, 3 data points) which allows determining the percentage of growth inhibition.
For more information, see Desjardins et al. (Antimicrob. Agents Chemother., 16(6), 710, 1979)."

(Post originally authored by Alice Williamson)

Strings:

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OSM-S-292 MMV689969

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OSM-S-293 MMV663915

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OSM-S-294 MMV689970

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OSM-S-295 MMV689971

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OSM-S-296 MMV689972

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OSM-S-297 MMV689973

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OSM-S-298 MMV689974

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OSM-S-299 MMV689975

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OSM-S-300 MMV689976

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OSM-S-301 MMV689977

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Attached Files
8th November 2015 @ 23:13

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.

 DGFA Compounds Assayed from OSM Series 1

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

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OSM-S-39

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OSM-S-111

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This post originally authored by Mat Todd

Attached Files