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Coumarin derivatives from Ainsliaea fragrans and their anticoagulant activity.

Lei L, Xue YB, Liu Z, Peng SS, He Y, Zhang Y, Fang R, Wang JP, Luo ZW, Yao GM, Zhang JW, Zhang G, Song HP, Zhang YH - Sci Rep (2015)

Bottom Line: In a search for safe and effective anticoagulant compounds from Chinese herbal medicine, a screening procedure on the whole plant of Ainsliaea fragrans was performed.Enantioseparation of 1 and 2 produced optically pure compounds 1a, 1b, 2a and 2b.The absolute configurations of the new compounds were confirmed by single-crystal X-ray diffraction analysis.

View Article: PubMed Central - PubMed

Affiliation: Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.

ABSTRACT
Coumarin derivatives are an important class of C6-C3 plant metabolites that show a variety of bioactivities. Currently, most clinical anticoagulant agents are coumarins, such as warfarin, dicoumarol and acenocoumarol, and patients taking these drugs must be monitored for adverse reactions. In a search for safe and effective anticoagulant compounds from Chinese herbal medicine, a screening procedure on the whole plant of Ainsliaea fragrans was performed. The phytochemical investigation of this plant afforded five new coumarin derivatives, including a pair of natural 4-hydroxycoumarin enantiomers (1), a pair of coumarin enantiomers with a rare polycyclic pyrano[3-2c] carbon skeleton (2) and a 7-hydroxycoumarin derivative (3), together with 5 known biogenetically related compounds (4-8). Enantioseparation of 1 and 2 produced optically pure compounds 1a, 1b, 2a and 2b. The absolute configurations of the new compounds were confirmed by single-crystal X-ray diffraction analysis. In addition, we evaluated the anticoagulant activity of all isolates via activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) assays in vitro and in vivo. Of note, compound 3 displayed potent anticoagulant activity and no significant hepatic or renal toxicity, which could make it a promising agent for further preclinical evaluation for preventing abnormal blood clotting.

No MeSH data available.


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Isolated compounds from extracts of Ainsliaea fragrans.
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f1: Isolated compounds from extracts of Ainsliaea fragrans.

Mentions: Compound 1 was obtained as colourless needles. Its molecular formula, C20H26O4, was determined by HRESIMS at m/z 331.1894 [M + H+] [calcd. for C20H27O4+m/z 331.1904], indicating eight degrees of unsaturation. The IR spectrum of 1 showed absorption bands assignable to a benzene group and a conjugated ester group (1601 and 1645 cm−1). The 1H NMR spectrum showed three aromatic olefinic protons at δH 7.01 (br d, J = 7.4 Hz, H-6), 7.34 (dd, J = 7.4, 8.0 Hz, H-7) and 7.24 (br d, J = 8.0 Hz, H-8); five methyl signals at δH 1.58 (s, H3-17), 1.67 (s, H3-18), 2.78(s, H3-21), 1.54 (d, J = 7.3 Hz, H3-20) and 1.50 (s, H3-19); and two methylene signals at δH 1.98 (m, H-13) and 2.26 (m, H-14). (Table 1) The 13C NMR and DEPT spectra revealed the presence of 20 carbon resonances, including one conjugated ester, ten olefinic carbons, five methyls, and two methylenes. The presence of a 1, 2, 3-trisubstituted phenyl moiety was supported by the NMR information as follows: δH 7.01 (H-6) to δC 128.8 (C-6), δH 7.34 (H-7) to δC 132.2 (C-7), and δH 7.24 (H-8) to δC 116.1 (C-8). A characteristic single peak (δH 2.78, δC 24.9) suggested an aromatic methyl. The 1D NMR data of 1 were similar to those of cyclobrachycoumarin222324, which indicated that 1 was a 5-methylcoumarin derivative. Of the 20 carbon resonances, ten were typical of a 5-methylcoumarin moiety, whereas the additional ten carbons consisted of two isoprene moieties, as shown by HMBC correlations from H-11 to C-12/C-20/C-19, from H3-20 to C-11/C-3/C-12, from H3-19 to C-11/C-12/C-13, and from H3-18/H3-17 to C-16/C-15. The two isoprene moieties were connected by C-13 and C-14, as shown by the 1H-1H COSY spectrum vicinal couplings between H-14 (δ 2.26) and H-13 (δ 1.98). Furthermore, the 5-methylcoumarin moiety and the isoprene side-chain were connected at C-3, as shown by the HMBC correlations from H-11 to C-3/C-4 and from H3-20 to C-3/C-11. All of these signals suggested that 1 was a C-3 substituted 5-methylcoumarin. (Fig. 1)


Coumarin derivatives from Ainsliaea fragrans and their anticoagulant activity.

Lei L, Xue YB, Liu Z, Peng SS, He Y, Zhang Y, Fang R, Wang JP, Luo ZW, Yao GM, Zhang JW, Zhang G, Song HP, Zhang YH - Sci Rep (2015)

Isolated compounds from extracts of Ainsliaea fragrans.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4551958&req=5

f1: Isolated compounds from extracts of Ainsliaea fragrans.
Mentions: Compound 1 was obtained as colourless needles. Its molecular formula, C20H26O4, was determined by HRESIMS at m/z 331.1894 [M + H+] [calcd. for C20H27O4+m/z 331.1904], indicating eight degrees of unsaturation. The IR spectrum of 1 showed absorption bands assignable to a benzene group and a conjugated ester group (1601 and 1645 cm−1). The 1H NMR spectrum showed three aromatic olefinic protons at δH 7.01 (br d, J = 7.4 Hz, H-6), 7.34 (dd, J = 7.4, 8.0 Hz, H-7) and 7.24 (br d, J = 8.0 Hz, H-8); five methyl signals at δH 1.58 (s, H3-17), 1.67 (s, H3-18), 2.78(s, H3-21), 1.54 (d, J = 7.3 Hz, H3-20) and 1.50 (s, H3-19); and two methylene signals at δH 1.98 (m, H-13) and 2.26 (m, H-14). (Table 1) The 13C NMR and DEPT spectra revealed the presence of 20 carbon resonances, including one conjugated ester, ten olefinic carbons, five methyls, and two methylenes. The presence of a 1, 2, 3-trisubstituted phenyl moiety was supported by the NMR information as follows: δH 7.01 (H-6) to δC 128.8 (C-6), δH 7.34 (H-7) to δC 132.2 (C-7), and δH 7.24 (H-8) to δC 116.1 (C-8). A characteristic single peak (δH 2.78, δC 24.9) suggested an aromatic methyl. The 1D NMR data of 1 were similar to those of cyclobrachycoumarin222324, which indicated that 1 was a 5-methylcoumarin derivative. Of the 20 carbon resonances, ten were typical of a 5-methylcoumarin moiety, whereas the additional ten carbons consisted of two isoprene moieties, as shown by HMBC correlations from H-11 to C-12/C-20/C-19, from H3-20 to C-11/C-3/C-12, from H3-19 to C-11/C-12/C-13, and from H3-18/H3-17 to C-16/C-15. The two isoprene moieties were connected by C-13 and C-14, as shown by the 1H-1H COSY spectrum vicinal couplings between H-14 (δ 2.26) and H-13 (δ 1.98). Furthermore, the 5-methylcoumarin moiety and the isoprene side-chain were connected at C-3, as shown by the HMBC correlations from H-11 to C-3/C-4 and from H3-20 to C-3/C-11. All of these signals suggested that 1 was a C-3 substituted 5-methylcoumarin. (Fig. 1)

Bottom Line: In a search for safe and effective anticoagulant compounds from Chinese herbal medicine, a screening procedure on the whole plant of Ainsliaea fragrans was performed.Enantioseparation of 1 and 2 produced optically pure compounds 1a, 1b, 2a and 2b.The absolute configurations of the new compounds were confirmed by single-crystal X-ray diffraction analysis.

View Article: PubMed Central - PubMed

Affiliation: Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.

ABSTRACT
Coumarin derivatives are an important class of C6-C3 plant metabolites that show a variety of bioactivities. Currently, most clinical anticoagulant agents are coumarins, such as warfarin, dicoumarol and acenocoumarol, and patients taking these drugs must be monitored for adverse reactions. In a search for safe and effective anticoagulant compounds from Chinese herbal medicine, a screening procedure on the whole plant of Ainsliaea fragrans was performed. The phytochemical investigation of this plant afforded five new coumarin derivatives, including a pair of natural 4-hydroxycoumarin enantiomers (1), a pair of coumarin enantiomers with a rare polycyclic pyrano[3-2c] carbon skeleton (2) and a 7-hydroxycoumarin derivative (3), together with 5 known biogenetically related compounds (4-8). Enantioseparation of 1 and 2 produced optically pure compounds 1a, 1b, 2a and 2b. The absolute configurations of the new compounds were confirmed by single-crystal X-ray diffraction analysis. In addition, we evaluated the anticoagulant activity of all isolates via activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) assays in vitro and in vivo. Of note, compound 3 displayed potent anticoagulant activity and no significant hepatic or renal toxicity, which could make it a promising agent for further preclinical evaluation for preventing abnormal blood clotting.

No MeSH data available.


Related in: MedlinePlus