In this work, we studied the effects of the N-alkyl group (methyl, cyclopentyl) in the piperazine ring of, respectively, rifampicin (RIF) and rifapentine (RPT) to correlate this substitution with their differential pharmacokinetic properties and overall clinical performance. Since this group is their only structural change, and given that they share the same pharmacological target, differences in their therapeutic behavior may respond to this asset, particularly in their interaction with lipid membranes across the organism. In this study, surface pressure-area isotherms, as well as spectroscopic and microscopic techniques of characterization of phospholipid monolayers at the air/water interface were used to gain insight into drug-membrane interactions. Differences in the affinity for lipid membranes for both drugs, given by the vibration frequency of characteristic chemical groups in the lipid, as well as by reflectivity and mean molecular area of the monolayer, seems to be due to the N-alkyl substituent and can contribute to provided a molecular explanation as why they pose different choices in the chemotherapy against the deadliest infectious disease, tuberculosis.

在这项工作中，我们研究了N的影响利福平（RIF）和利福喷丁（RPT）的哌嗪环中的-烷基（甲基，环戊基）将这种取代与其差异的药代动力学特性和整体临床性能相关联。由于该组是它们唯一的结构变化，并且鉴于它们具有相同的药理学靶标，因此其治疗行为上的差异可能对此资产有反应，尤其是它们与整个生物体中脂膜的相互作用。在这项研究中，使用了表面压力-面积等温线，以及在空气/水界面处表征磷脂单层的光谱和显微技术，以深入了解药物-膜之间的相互作用。两种药物对脂质膜亲和力的差异，N-烷基取代基可以帮助提供分子解释，说明为什么它们在针对最致命的传染病，结核病的化学疗法中会做出不同的选择。