Figure 5.

Drug combinations involving disulfiram. Disulfiram along with kanamycin, clozapine, amoxicillin and chlorpromazine are all predicted to be individually effective antileishmanial agents because they all act on both genes in a synthetic lethal pair. However, they also have the potential to act synergistically to produce growth inhibition in L. major. Therefore, for predictions of model-guided superadditivity, it is assumed that the interactive relationship present between genes in a synthetic lethal deletion would translate directly to any associated drug combinations. In panels A, B, C and D, the results of one concentration profile of disulfiram + kanamycin, disulfiram + clozapine, disulfiram + amoxicillin and disulfiram + chlorpromazine as evaluated against L. major promastigotes are presented, respectively. The theoretical additivity bar was computed using the bliss additivity metric upon comparing the effects of the individual drugs. A two-sample t-test comparing two means was used to determine statistical significance between the theoretical and experimental combinations. Concentrations are provided in parentheses. Error bars signify standard error. The y-axis indicates fractional experimental effect of inhibition or growth relative to "No Drug" control (0 equals no inhibition, 1 equals max inhibition). All data were generated at 48 hours post addition of alamarBlue dye.

Chavali et al. BMC Systems Biology 2012 6:27   doi:10.1186/1752-0509-6-27
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