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. 2019 Jun 7;24(11):2156.
doi: 10.3390/molecules24112156.

Design, Synthesis and Anti-Platelet Aggregation Activity Study of Ginkgolide-1,2,3-triazole Derivatives

Jian Cui  1 , Le'An Hu  2   3 , Wei Shi  4 , Guozhen Cui  5 , Xumu Zhang  6 , Qing-Wen Zhang  7
Affiliations

Design, Synthesis and Anti-Platelet Aggregation Activity Study of Ginkgolide-1,2,3-triazole Derivatives

Jian Cui et al. Molecules. .

Abstract

Ginkgolides are the major active component of Ginkgo biloba for inhibition of platelet activating factor receptor. An azide-alkyne Huisgen cycloaddition reaction was used to introduce a triazole nucleus into the target ginkgolide molecules. A series of ginkgolide-1,2,3-triazole conjugates with varied functional groups including benzyl, phenyl and heterocycle moieties was thus synthesized. Many of the designed derivatives showed potent antiplatelet aggregation activities with IC50 values of 5~21 nM.

Keywords: ginkgolide; inhibitor; platelet-activating factor receptor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Formation of 10-O-propargylated ginkgolides 3, 3′ and 3″.
Scheme 2
Scheme 2
Formation of 10-substituted 1,2,3-triazole-ginkgolide derivatives 5, 5′ and 5″.
Scheme 3
Scheme 3
Preparation of azides 4a–4ee.
Scheme 4
Scheme 4
Preparation of azides 4ff, 4gg.
Figure 1
Figure 1
Structures of 10-substituted 1,2,3-triazole-ginkgolide B derivatives 5a–5gg.
Figure 2
Figure 2
Structures of 10-substituted 1,2,3-triazole-ginkgolide A derivatives 5′a-5′gg and 10-substituted 1,2,3-triazole-ginkgolide C derivatives 5″a-5″gg.
Figure 3
Figure 3
Antiplatelet aggregation activities of the 10-substituted 1,2,3-triazole-ginkgolide B derivatives. Ginkgolide B (1) was used as reference.
Figure 4
Figure 4
Antiplatelet aggregation activity activities of the 10-substituted 1,2,3-triazole-ginkgolide A and ginkgolide C derivatives. Ginkgolide B (1), ginkgolide A (1′) and ginkgolide C (1″) were used as reference.
Figure 5
Figure 5
Cytotoxicity of some of ginkgolide-1,2,3-triazole derivatives: (a) Tested at 1 μM concentration. (b) Tested at 10 μM concentration. Ginkgolide B (1) was used as reference.
Figure 6
Figure 6
Toxicity on platelets of some of ginkgolide-1,2,3-triazole derivatives: (a) Tested at 1 μM concentration. (b) Tested at 10 μM concentration. Ginkgolide B (1) was used as reference.
See this image and copyright information in PMC

References

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