Labdane-type diterpenes: thermal effects on phospholipid bilayers, incorporation into liposomes and biological activity

被引:32
作者
Matsingou, C
Hatziantoniou, S
Georgopoulos, A
Dimas, K
Terzis, A
Demetzos, C
机构
[1] Univ Athens, Sch Pharm, Dept Pharmaceut Technol, GR-15771 Athens, Greece
[2] Acad Athens, Fdn BioMed Res, Lab Pharmacolpharmacotechnol, GR-10673 Athens, Greece
[3] NCSR Demokritos, Xray Lab, Athens 15310, Greece
关键词
labdane diterpene; differential scanning calorimetry; liposome; DPPC; cytotoxicity;
D O I
10.1016/j.chemphyslip.2005.07.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Labd-13(E)-ene-8 alpha,15-diol (1) and its derivative labd-13(E)-ene-8 alpha-ol-15-yl-acetate (2) are water insoluble biological active molecules and their structures were elucidated using NMR and X-ray techniques. Differential scanning calorimetry (DSC) was applied to study the thermal effects of 1 and 2 on DPPC bilayers. Liposomes composed of egg phosphatidylcholine/dipalmytoylphosphatidyl-glycerol (9:0.1 molar ratio) were prepared by the thin-film hydration method and were used for incorporating 1 and 2. Free and liposomal 1 and 2 were tested for their activity against human cancer cell lines using the sulphorhodamine B assay. The effect of 1 and 2 on DPPC bilayers caused abolition of the pre-transition temperature, lowering of the main phase transition and reduction of the transition enthalpy only in the presence of cholesterol. The liposomes that have been designed and developed offer high incorporation efficiency; 62.4% (0.369 drug/lipid molar ratio) and 99.7% (0.661 drug/lipid molar ratio) for 1 and 2, respectively. Liposomal 2 showed growth-inhibiting activity against the majority of the tested cell lines. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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页码:1 / 11
页数:11
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