Sinha Ragini, Srivastava Sudha, Joshi Akshada, Joshi Urmila J, Govil Girjesh
National Facility for High Field NMR, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.
National Facility for High Field NMR, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.
Eur J Med Chem. 2014 May 22;79:102-9. doi: 10.1016/j.ejmech.2014.04.002. Epub 2014 Apr 2.
Flavonols are an important class of naturally occurring molecules and are known for their pharmacological activity. The activity is associated with the ability of flavonols to influence membrane-dependent processes. We have investigated the in-vitro anti-proliferative and anti-oxidant activity of galangin (GLN), fisetin (FTN) and quercetin (QTN), which possess variable number of phenolic hydroxyl groups. An attempt has been made to correlate the biological activity of these molecules with their interaction and localization in dipalmitoyl phosphatidyl choline (DPPC) bilayers, using differential dcanning calorimetry (DSC) and nuclear magnetic resonance (NMR) methods. Results indicate that GLN interacts to the alkyl chains of the lipid bilayer involving hydrophobic interactions. FTN and QTN interact with head region and sn-1-glycero region involving hydrogen bonding. Ring current induced chemical shifts of lipid protons, due to intermolecular interaction indicate that GLN acquires a parallel orientation with respect to the bilayer normal whereas FTN and QTN resume a mixed orientation. The membrane binding constants of these molecules are in the order GLN > QTN > FTN. It has been shown that the number and position of hydroxyl groups in these molecules play an important role in membrane binding and thereby in biological activity.
黄酮醇是一类重要的天然存在的分子，以其药理活性而闻名。这种活性与黄酮醇影响膜相关过程的能力有关。我们研究了高良姜素（GLN）、非瑟酮（FTN）和槲皮素（QTN）的体外抗增殖和抗氧化活性，它们具有不同数量的酚羟基。我们尝试使用差示扫描量热法（DSC）和核磁共振（NMR）方法，将这些分子的生物活性与其在二棕榈酰磷脂酰胆碱（DPPC）双层中的相互作用和定位联系起来。结果表明，GLN通过疏水相互作用与脂质双层的烷基链相互作用。FTN和QTN通过氢键与头部区域和sn-1-甘油区域相互作用。由于分子间相互作用导致的脂质质子的环电流诱导化学位移表明，GLN相对于双层法线呈平行取向，而FTN和QTN则呈混合取向。这些分子的膜结合常数顺序为GLN > QTN > FTN。结果表明，这些分子中羟基的数量和位置在膜结合以及生物活性中起着重要作用。
