RESUMO
Dehydroepiandrosterone (DHEA) is an FDA-approved food supplement used as an assisted reproductive sex hormone. The bioavailability is severely limited by its poor solubility (23 µg/mL). Herein, we aimed to modulate its solubility through cocrystallization. Eight cocrystals of DHEA with pyrocatechol (CAT), hydroquinone (HQ), resorcinol (RES), phloroglucinol (PG), 1,5-dihydroxy naphthalene (DHN), p-hydroxybenzoic acid (PHBA), gallic acid (GA), and 5-hydroxyisophthalic acid (5HIPA) were designed and synthesized. Some basic characterization tools, including powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, and Fourier transform infrared spectroscopy, were also applied in our work for basic analyses of cocrystals. It is indicated that DHEA-GA exhibits its superiority in dissolution and pharmacokinetic behaviors. While the area under the curve values of DHEA-GA is improved at the ratio of 2.2, the corresponding bioavailability of DHEA is expected to be accordingly increased.
RESUMO
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most versatile human pathogens. Luteolin (LUT) has anti-MRSA activity by disrupting the MRSA cytoplasmic membrane. However, the mechanism by which luteolin disrupts the membrane remains unclear. Here, we performed differential scanning calorimetry (DSC) and all-atomic molecular dynamics (AA-MD) simulations to investigate the interactions and effects of LUT on model membranes composed of phosphatidylcholine (PC) and phosphatidylglycerol (PG). We detected the transition thermodynamic parameters of dipalmitoylphosphatidylcholine (DPPC) liposomes, dipalmitoylphosphatidylglycerol (DPPG) liposomes, and liposomes composed of both DPPC and DPPG at different LUT concentrations and showed that LUT molecules were located between polar heads and the hydrophobic region of DPPC/DPPG. In the MD trajectories, LUT molecules ranging from 5 to 50 had different effects on the membranes thickness, fluidity and ordered property of lipids, and lateral pressure of lipid bilayers composed of dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylglycerol (DOPG). Also, most LUT molecules were distributed in the region between the phosphorus atoms and C9 atoms of DOPC and DOPG. On the basis of the combination of these results, we conclude that the distinct effects of LUT on lipid bilayers composed of PCs and PGs may elucidate the mechanism by which LUT disrupts the cytoplasmic membrane of MRSA.
