Title: Combinations of lipophilic drugs show increased synergy
Speaker: Murat Cokol
Date/Time: March 18, Wednesday, 12:40 - 13:30
Place: FENS G032
Abstract: When drugs are combined, they can have an increased effect given the effect of the individual drugs, in a phenomenon called drug synergy. Understanding and predicting synergistic drug interactions is important for treatment success. We have previously shown that combinations of lipophilic antifungals are often synergistic against yeast (S. cerevisiae) growth. In this study, we conducted in vitro checkerboard assays of drug interactions for all pairwise combinations of 25 antibiotics in bacteria (E. coli), corresponding to 300 drug interaction tests. We assessed the concavity of isobolograms for growth-inhibition levels as a measure of drug interaction. We found 46 synergistic drug pairs. 25 antibiotics used in this screen were chosen to cover a wide range of lipophilicity scores (XLogP3), as reported by PubChem. We compared the lipophilicity of the antibiotics with their propensity to participate in synergistic drug interactions. In agreement with previous observations in yeast, we found that lipophilic antibiotics are significantly more likely to show synergy in E. coli. In addition, we found that antibiotics pairs where both antibiotics are lipophilic are significantly more likely to show synergy. Our results exhibit that combinations of lipophilic drugs are more likely to show synergy in two distant species, E. coli and S. cerevisiae. This observation provides a successful and cheap prediction method for drug synergy and gives insights on the bioavailability model for drug interactions.