A series of novel pleuromutilin derivatives containing nitrogen groups on the side chain of C14 were synthesized under mild conditions. Most of the synthesized derivatives displayed potent antibacterial activities. Compound 9 was found to be the most active antibacterial derivative against MRSA (MIC = 0.06 μg/mL). Furthermore, the result of time-kill curves showed that compound 9 had a certain inhibitory effect against MRSA in vitro. Moreover, according to a surface plasmon resonance (SPR) study, compound 9 (KD = 1.77 × 10−8 M) showed stronger affinity to the 50S ribosome than tiamulin (KD = 2.50 × 10−8 M). The antibacterial activity of compound 9 was further evaluated in an MRSA-infected murine thigh model. Compared to the negative control group, tiamulin reduced MRSA load (~0.7 log10 CFU/mL), and compound 9 performed a treatment effect (~1.3 log10 CFU/mL). In addition, compound 9 was evaluated in CYP450 inhibition assay and showed only moderate in vitro CYP3A4 inhibition (IC50 = 2.92 μg/mL). 相似文献
Multiphase flow in porous media is strongly influenced by the pore-scale arrangement of fluids. Reservoir-scale constitutive relationships capture these effects in a phenomenological way, relying only on fluid saturation to characterize the macroscopic behavior. Working toward a more rigorous framework, we make use of the fact that the momentary state of such a system is uniquely characterized by the geometry of the pore-scale fluid distribution. We consider how fluids evolve as they undergo topological changes induced by pore-scale displacement events. Changes to the topology of an object are fundamentally discrete events. We describe how discontinuities arise, characterize the possible topological transformations and analyze the associated source terms based on geometric evolution equations. Geometric evolution is shown to be hierarchical in nature, with a topological source term that constrains how a structure can evolve with time. The challenge associated with predicting topological changes is addressed by constructing a universal geometric state function that predicts the possible states based on a non-dimensional relationship with two degrees of freedom. The approach is validated using fluid configurations from both capillary and viscous regimes in ten different porous media with porosity between 0.10 and 0.38. We show that the non-dimensional relationship is independent of both the material type and flow regime. We demonstrate that the state function can be used to predict history-dependent behavior associated with the evolution of the Euler characteristic during two-fluid flow.
Transport in Porous Media - A macroscopic model that accounts for the effect of momentum dispersion on flows in porous media is proposed. The model is based on the pore scale prevalence hypothesis... 相似文献
Transport in Porous Media - The effective slip length at the interface between pure fluid flow and porous media composed of packed spheres has been accurately characterized. In this study, as the... 相似文献
Nonlinear Dynamics - This paper describes the chaos behavior of an in-plane tethered satellite system induced by atmospheric drag and the Earth’s oblateness. A commonly used model, the... 相似文献
Nonlinear Dynamics - This paper proposes a novel stability condition for delayed fractional-order composite systems. First, we extend the vector Lyapunov function to the fractional-order systems to... 相似文献