Ionization Constants of Ginkgolide B in Aqueous Solution

Zekri, Oussama; Boudeville, Philippe; Genay, Philippe; Perly, Bruno; Braquet, P.; Jouenne, Philippe; Burgot, Jean‐Louis

doi:10.1021/ac950939g

Cited by 40 publications

(28 citation statements)

References 12 publications

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“…In a third step, the deprotection of the methylenedioxy bridge of 7 was obtained by acid treatment in a dioxane-water mixture and led to 4 in a good yield (89%). The maximal water solubility of 4, as assessed by HPLC with UV detection, was 0.018 g/l, a value at least 15-fold lower than that obtained for ginkgolides C and B (i.e., 0.3 g/l) [Zekri et al, 1996].…”

Section: Results Chemistrymentioning

confidence: 56%

“…Indeed, quantitative estimation of the lipophilicity of a biologically active molecule is widely used to establish structure/activity relationships [Van de Waterbeemd and Testa, 1987]. The maximal water solubility of 4, as assessed by HPLC, is significantly lower than that reported for ginkgolide B [Zekri et al, 1996]. Considering previous studies of HPLC retention time, which showed that ginkgolide C is more hydrophilic than ginkgolide B [Braquet, 1987], it can thus be inferred that 4 is significantly more lipophilic than ginkgolide C. Because it is a typical drug-membrane interaction, PAF inhibition by ginkgolides increases as their polarity decreases [Braquet, 1987].…”

Section: Chemistrymentioning

confidence: 99%

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Synthesis and biological studies of a new ginkgolide C derivative: Evidence that the cardioprotective effect of ginkgolides is unrelated to PAF inhibition

Pietri¹,

Liebgott²,

Finet³

et al. 2001

Drug Development Research

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Ginkgolides have been demonstrated to protect the myocardium in experimental ischemiareperfusion, but the extent to which this property is not related to platelet-activating factor (PAF) inhibition remains debated. This study was undertaken to determine whether a ginkgolide devoid of any anti-PAF activity could retain a cardioprotective activity. For this purpose, a new ginkgolide C (3) analogue, 7-O-(4-methylphenyl) ginkgolide C (4), was obtained from 3 with retention of configuration, using, in the key step, a copper-catalyzed arylation with tris-(4-methylphenyl) bismuth diacetate. No PAF inhibition on rabbit platelets in vitro was found for 4 up to 1.2.10 -4 M. However, 4 was found a significantly better preserving agent than 3 or ginkgolide B, a potent PAF inhibitor (all drugs at 0.35 µM), on hemodynamic and metabolic (i.e., myocardial ATP contents and enzymatic activities) indices measured in rat isolated hearts undergoing ischemia-reperfusion. The data provide additional support to a PAF-unrelated pharmacological activity for ginkgolides. Because the water solubility of 4, estimated by high-performance liquid chromatography analysis, was significantly lower than that of the parent molecule 3, a likely mechanism for the protective action of 4 involves its increased affinity for the myocardium, as compared to the relatively more hydrophilic 3. Drug Dev. Res. 54:191-201, 2001.

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Section: Results Chemistrymentioning

confidence: 56%

Section: Chemistrymentioning

confidence: 99%

Synthesis and biological studies of a new ginkgolide C derivative: Evidence that the cardioprotective effect of ginkgolides is unrelated to PAF inhibition

Pietri¹,

Liebgott²,

Finet³

et al. 2001

Drug Development Research

View full text Add to dashboard Cite

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“…In all cases care should be taken to avoid water because of hygroscopicity, and the risk of lactone ring opening, which occurs at pH above 6. 12 We used two different instruments, both of the FT-type with PEM modulation of the IR light. The instrument at the Quantum Protein Centre, Copenhagen, Denmark, is a Thermo Nicolet Nexus 870 infrared spectrometer equipped with a single PEM and improved with a filter that only allowed light in the range between 1000 and 1750 cm 21 Here, an extra PEM is added after the sample, eliminating most of the linear birefringence (LB) artifacts that often occur.…”

Section: Materials and Methods Ir And Vcd Spectroscopymentioning

confidence: 99%

Structure and absolute configuration of ginkgolide B characterized by IR‐ and VCD spectroscopy

et al. 2009

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Experimental and calculated (B3LYP/6-31G(d)) vibrational circular dichroism (VCD) and IR spectra are compared, illustrating that the structure and absolute configuration of ginkgolide B (GB) may be characterized directly in solution. A conformational search for GB using MacroModel and subsequent DFT optimizations (B3LYP/6-31G(d)) provides a structure for the lowest energy conformer which agrees well with the structure determined by X-ray diffraction. In addition, a conformer at an energy of 7 kJ mol(-1) (B3LYP/6-311+G(2d,2p)) with respect to the lowest energy conformer is predicted, displaying different intramolecular hydrogen bonding. Differences between measured and calculated IR and VCD spectra for GB at certain wavenumbers are rationalized in terms of interactions with solvent, intermolecular GB-GB interactions, and the potential presence of more than one conformer. This is the first detailed investigation of the spectroscopic fingerprint region (850-1300 cm(-1)) of the natural product GB employing infrared absorption and VCD spectroscopy.

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“…[144] Ginkgolides contain three lactones (rings C, E, and F, Figure 3) and hence their structures in solution are highly dependent on the pH value of the media in which they are dissolved. Zekri et al determined the ionization constants of ginkgolides by 1 H NMR titrations, [145] which showed that the lactones start to open at around pH 7. At pH 8, the predominant species (% 50 %) is the form in which only ring F is open; ring E is open to a lesser extent (% 20 %).…”

Section: Synthetic Modification Of Parent Compoundsmentioning

confidence: 99%

Chemistry and Biology of Terpene Trilactones fromGinkgo Biloba

2004

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Ginkgo biloba, the ginkgo tree, is the oldest living tree, with a long history of use in traditional Chinese medicine. In recent years, the leaf extracts have been widely sold as phytomedicine in Europe and as a dietary supplement worldwide. Effects of Ginkgo biloba extracts have been postulated to include improvement of memory, increased blood circulation, as well as beneficial effects to sufferers of Alzheimer's disease. The most unique components of the extracts are the terpene trilactones, that is, ginkgolides and bilobalide. These structurally complex molecules have been attractive targets for total synthesis. Terpene trilactones are believed to be partly responsible for the neuromodulatory properties of Ginkgo biloba extracts, and several biological effects of the terpene trilactones have been discovered in recent years, making them attractive pharmacological tools that could provide insight into the effects of Ginkgo biloba extracts.

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Ionization Constants of Ginkgolide B in Aqueous Solution

Cited by 40 publications

References 12 publications

Synthesis and biological studies of a new ginkgolide C derivative: Evidence that the cardioprotective effect of ginkgolides is unrelated to PAF inhibition

Synthesis and biological studies of a new ginkgolide C derivative: Evidence that the cardioprotective effect of ginkgolides is unrelated to PAF inhibition

Structure and absolute configuration of ginkgolide B characterized by IR‐ and VCD spectroscopy

Chemistry and Biology of Terpene Trilactones fromGinkgo Biloba

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