The Use of Differential Scanning Calorimetry to Study the Thermal Effects of Structurally Similar Pregnane Analogs

Differential scanning calorimetry (DSC) is a valuable technique to study drug: membrane interactions. We have studied the thermotropic properties of nine pregnane analogs with known biological activity. Structure activity relationships were revealed for the nine molecules possessing different activities between the lowering of main phase transition ( T c ) of dipalmitoyl phosphatidylcholine bilayers and increase of the half width of the main phase transition (Δ T C1/2 ). The lowering of T c and increase of Δ T c1/2 broadly paralleled the reported biological activity. This consistent qualitative trend was prominently observed at a molar ratio of 10% ( x = 0.10), whereas higher steroid concentrations introduced deviations. Thus, it appears that x = 0.10 is a compromise concentration to obtain the optimum results. These findings show that DSC is sensitive to subtle stereochemical differences in pregnane analogs, revealing a qualitative correlation with bilayer perturbation, although physical disruption of an idealized DPPC matrix alone does not fully predict in vivo anesthetic potency. More studies are required to reveal the molecular reasons for observing such differences.