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10th January 2012 @ 02:33
Analysis of PMY 2-4, PMY 6-1, PMY 10-2 (TCMDC-123812), PMY 11-2 (TCMDC-123794), PMY 12-1 and PMY 14-1 (acyl near neighbour) by GSK Tres Cantos courtesy of Felix Calderon.

Assay details have been previously reported and are provided in the supporting information.

IC50 48hrs:
PMY 10-2 (TCMDC-123812) 0.818 μM
PMY 11-2 (TCMDC-123794) 0.245 μM
PMY 14-1 0.047 μM
Atovaquone 0.001 μM
Pirimethamine 0.033 μM
Artesunate 0.019 μM
Chloroquine 0.052 μM

GSK Data


See also:
Second Analysis of First Set of Compounds (Avery)
First Set of Biological Data
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Attached Files
8th January 2012 @ 11:00
Vicky Avery and team at the Eskitis Institute in Queensland evaluated the same set of compounds as Ralph/Pham. Data sent to Sydney on 19th Dec 2011. Posting here on their behalf.

Experimental:

The attached excel has the IC50 values determined from 21 point dose response curves for both K1 and 3D7 strains. This was performed in two separate screening rounds, 4 data points per dose. Plus, HEK-293 cytox data - duplicate point single experiment.

Avery Data (Excel)


(Please note that Sandra noticed a discrepancy between the electronic numbering system she was sent and the accompanying paper copy of structures and corresponding compound ID's. She has noted this in the attached excel file. Explanation from Paul Ylioja: the paper copy of structures included contained the batch number sent to GSK (14-1). 14-3 is a newer batch of the same compound.)
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8th January 2012 @ 10:44
Performed by James Pham and Stuart Ralph, University of Melbourne. Posted here on their behalf. Data posted in full below, but were first discussed here with graphical description of data here.

Data for compounds 1-8 (also short link)

Data for compounds 9-16 (also short link)

Repeat analysis of compounds 1-9

Depiction of First Results (image)

First Results (chemdraw)


Experimental description from James Pham:

For the two known TCMDC compounds - PMY10-2 & PMY11-2 - the XC50 were 331.14 nM and 53.87 nM respectively (source: ChEMBL db) where the original authors 'denominated this parameter XC50 to indicate that it is an estimation of the usual IC50 values.' They had used a colorimetric assay using LDH activity as a measure of growth as it is very amenable to high throughput screening.

For our first trial, the two compounds inhibition profiles were quite similar with both IC50 estimated around 500 nM, but this is hard to say with any certainty, reason being at 1 uM the curve may not have reached a plateau. And other issues of variability as mentioned in my earlier emails.

The screening of these compounds was performed using a malaria SYBR green I- based fluorometric assay. The assay uses SYBR green I, which fluoresces when bound to DNA and is used as an index of growth for Plasmodium falciparum parasites in whole erythrocytes. Asynchronous parasites (standard laboratory strain 3D7) were prepared in 96-well plates for a twofold-dilution of the compounds (highest concentration = 1000 nM). Chloroquine was used as a positive control, negative control was vehicle alone (1% DMSO) and a lane of red blood cells served for subtraction of background. Parasites were grown for 48 hours (Gamo et al paper did 72hr incubation to include possible delay death effects).
Depiction of First Results (image)
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Attached Files