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抗癌药物米托蒽醌与牛磺脱氧胆酸钠(NaTDC)和牛磺胆酸钠(NaTC)胆盐相互作用的光谱研究。

Spectroscopic Investigation of the Interaction of the Anticancer Drug Mitoxantrone with Sodium Taurodeoxycholate (NaTDC) and Sodium Taurocholate (NaTC) Bile Salts.

作者信息

Enache Mirela, Toader Ana Maria, Neacsu Victoria, Ionita Gabriela, Enache Madalin I

机构信息

Institute of Physical Chemistry Ilie Murgulescu, Romanian Academy, Splaiul Independentei 202, Bucharest 060021, Romania.

Institute of Biology, Romanian Academy, Splaiul Independentei 296, Bucharest 060031, Romania.

出版信息

Molecules. 2017 Jun 28;22(7):1079. doi: 10.3390/molecules22071079.

Abstract

The focus of the present work was to investigate the interaction of the anticancer drug mitoxantrone with two bile salts, sodium taurodeoxycholate (NaTDC) and sodium taurocholate (NaTC). Ultraviolet-visible (UV-Vis) absorption and electron paramagnetic resonance (EPR) spectroscopy were used to quantify the interaction and to obtain information on the location of mitoxantrone in bile salt micelles. The presence of submicellar concentrations of both bile salts induces mitoxantrone aggregation and the extent of drug aggregation in NaTDC is higher than in NaTC. For micellar bile salts concentrations, mitoxantrone monomers are entrapped in the micellar core. Binding constants, micelle/water partition coefficients and the corresponding thermodynamic parameters for binding and partitioning processes were estimated using the changes in monomer absorbance in the presence of bile salts. Binding interaction of mitoxantrone is stronger for NaTDC than NaTC micelles, whereas partitioning efficiency is higher for NaTC micelles for all investigated temperatures. Thermodynamic parameters indicate that both binding and partitioning processes are spontaneous and entropy controlled. The spectral behavior and thermodynamic parameters indicate distinct types of mitoxantrone interaction with NaTDC and NaTC micelles supported by the differences in nature and structure of bile salts micelles.

摘要

本研究的重点是研究抗癌药物米托蒽醌与两种胆汁盐,即牛磺脱氧胆酸钠(NaTDC)和牛磺胆酸钠(NaTC)之间的相互作用。利用紫外可见(UV-Vis)吸收光谱和电子顺磁共振(EPR)光谱来量化这种相互作用,并获取米托蒽醌在胆汁盐胶束中位置的信息。两种胆汁盐亚胶束浓度的存在会诱导米托蒽醌聚集,且NaTDC中药物聚集的程度高于NaTC。对于胶束胆汁盐浓度,米托蒽醌单体被包裹在胶束核心中。利用胆汁盐存在下单体吸光度的变化估算了结合常数、胶束/水分配系数以及结合和分配过程的相应热力学参数。米托蒽醌与NaTDC胶束的结合相互作用比与NaTC胶束更强,而在所有研究温度下,NaTC胶束的分配效率更高。热力学参数表明结合和分配过程都是自发的且受熵控制。光谱行为和热力学参数表明,由于胆汁盐胶束性质和结构的差异,米托蒽醌与NaTDC和NaTC胶束存在不同类型的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a251/6152313/4ba0fced2506/molecules-22-01079-g001.jpg

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