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Molecules 2019, 24(19), 3628; https://doi.org/10.3390/molecules24193628

Article
Two New AChE Inhibitors Isolated from Li Folk Herb Heilaohu “Kadsura coccinea” Stems
1
Hainan Key Laboratory for Research and Development of Natural Products from Li Folk Medicine, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agriculture Sciences, Haikou 571101, China
2
College of Food Science and technology, Nanjing Agricultural University, Nanjing 210095, China
*
Correspondence: [email protected] (W.L.M.); [email protected] (H.F.D.); Tel./Fax: +86-0898-66968036 (H.F.D.)
These people were contributed equally.
Received: 11 September 2019 / Accepted: 7 October 2019 / Published: 8 October 2019

Abstract

:
Two new triterpenoids, named kadsuricoccins A and B, together with three known ones, were isolated from the Li folk herb Heilaohu, the stems of Kadsura coccinea (Lem.) A. C. Smith, which was used for food and as a healthy supplement. Their structures were elucidated by comprehensive analyses of mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopic data. To search healthy components, an acetylcholinesterase (AChE) inhibitory activity test by Ellman’s Method was conducted, kadsuricoccins A and B showed activity with the AChE inhibit index (AII) up to 68.96% ± 0.19% and 57.8% ± 0.11% at 94 nM (compared with positive control tacrine AII 79.80% ± 0.20%, 9.4 nM), respectively.
Keywords:
Kadsura coccinea; Schisandraceae; AChE inhibitor; triterpenoid

1. Introduction

With global exchange increase and dietary habit diversification, ethnic characteristic foods are becoming more and more popular. One of the unique ingredients of ethnic characteristic foods is their flavor agent, which could stimulate appetite, protect foods from spoilage and keep people healthy [1]. Living in the dangerous rainforest, the Li folk ancestors in Hainan Island had tested and screened out various herbs to treat disease and to improve their quality of life [2]. Among them, the Heilaohu [Kadsura coccinea (Lem.) A. C. Smith, Schisandraceae] fruit is a new taste, and its stems with their full aroma and sedative effect is used for pork and beef stew by the Li folk people [3]. The chemical constituents studied of this plant showed unique features in previous studies, and series of lignans [4], triterpenoids [5] and nor-terpenoids [6], with biological activities, were isolated [4,7]. To reveal the mechanism of action and explore new agents for health care, we studied K. coccinea stems (collected from the Li folk area) and found two new compounds, named kadsuricoccins A and B, and three known compounds: (22Z,24E)-3-oxoprotosta-27 12,22,24-trien-26-oic acid (3) [8], cycloartenone (4) [9] and 24-methyl-8-lanoten-3-one (5) [10] (Figure 1). We then tested their AChE inhibit activities to search for natural material in preventing Alzheimer’s Disease (AD). The isolation process, new compounds’ structural elucidation details and the AChE inhibit assay, were described in this paper.

2. Results and Discussion

Kadsuricoccins A (1) was isolated as colorless, amorphous powder. Its molecular formula of C23H34O3 was determined by the positive HRESIMS ion at m/z 381.2508 [M + Na]+ (calcd. for C23H34O5Na, 381.2508), indicative of seven degrees of unsaturation. The IR spectrum revealed the presence of carbonyl (1,712 and 1,691 cm−1) and double bonds (1,623 and 1,344 cm−1) absorptions. The 1H-NMR spectra (Table 1) of compound 1 exhibited signals of one methoxyl [δH 3.69 (3H, s, -OMe)], four methyls [δH 1.18 (3H, s, H-18), 0.90 (3H, s, H-19), 1.82 (3H, s, H-21) and 0.94(3H, s, H-22)], and three olefinic protons (δH 4.96 (1H, s, Ha-20), 4.84 (1H, s, Hb-20) and 6.65 (1H, dd, J = 3.4, 3.6 Hz, H-12). The 13C-NMR and DEPT spectroscopic data (Table 1) showed 23 carbon resonances, including five methyls (one methoxyl), eight methylenes (one olefinic), three methines (one olefinic) and seven quaternary carbons (two carbonyl and two olefinic). By comparing the NMR, compound 1 was similar to those of 16-oxo-mansumbin-3(28),13(17)-dien-3-oic-acid methyl ester [11], a rare octanordammarane (a kind of octanary nor-triterpenoid) except for the markedly different shifts at δC 131.4 (d, C-12), 144.1 (s, C-13), 36.1 (t, C-16) and 207.1 (s, C-17), instead of δC 27.3 (t, C-12), 187.0 (s, C-13), 209.0 (s, C-16) and 126.5 (s, C-17) in 16-oxo-mansumbin-3(28),13(17)-dien-3-oic-acid methyl ester, indicating that compound 1 was generated from 16-oxo-mansumbin-3(28),13(17)-dien-3-oic-acid methyl ester for the α,β- unsaturated lactone moved from C-13-C-17-C(=O)-16 to C-12-C-13-C(=O)-17. Furthermore, the determined molecular formula C15H22O4 and the key 1H-1H COSY correlations with H-11 [δH 2.21 (2H, m)]/H-12, H-15[δH 1.99 (1H, m) and 1.54 (1.54)]/H-16 [δH 2.46 (1H, m) and 2.28 (1H, m)], and the HMBC correlations from H-12 to C-17 (δC 27.3 t) and C-10 (δC 37.7 s), and from H-15 and H-16 to C-17 verified this hypothesis. The other 1H-1HCOSY and HMBC correlations (Figure 2) also confirmed this atom connectivity. The relative configuration of compound 1 was determined to be likely to the 16-oxo-mansumbin-3(28),13(17)-dien-3-oic-acid methyl ester (Figure 2) with β-oriented of C-19, H-10 [11], and C-22, and α-oriented of H-5 and C-18 by ROESY cross-peaks H-2 [δH 2.29 (1H, m)]/H-5 [δH 2.18 (1H, m)], H-19/H-9 [δH 2.25 (1H, m)], H-9/H-22, H-22/H-7β [δH 2.08 (1H, m)], and H-7α [δH 1.17 (1H, m)]/H-18. Thus, the structure of compound 1 was assigned as shown, and named kadsuricoccins A (1).
Kadsuricoccins B (2)’s molecular formula of C30H44O3 was determined by the positive HRESIMS ion at m/z 475.3183 [M + Na]+ (calcd. for C23H34O5Na, 381.2508) with nine degrees of unsaturation. The IR spectrum showed the presence of carbonyl (1705 cm−1) and double bonds (1457 and 1380 cm−1) absorptions. The 13C-NMR and DEPT spectroscopic data (Table 1) revealed 30 carbon resonances, including seven methyls, eight methylenes, six methines (three olefinic), and nine quaternary carbons (one ketone, one acidic, and three olefinic). By comparing the NMR, compound 2 was similar to those of kadindutic acid [12], except for the markedly different shifts at δC 37.5 (s, C-8), 46.9 (d, C-9), 121.5 (d, C-11), 126.6 (d, C-12), 140.3 (s, C-13), 138.8 (s, C-17) and 19.0 (q, C-30), instead of δC 135.7 (d, C-8), 134.2 (s, C-8), 33.3 (t, C-11), 29.3 (d, C-12), 143.8 (s, C-13), 134.6 (s, C-17) and 21.5 (q, C-30) in kadindutic acid, indicating compound 2 was generated from kadindutic acid for the double bond moved from C-8-C-9 to C-11-C-12, and the methyl group 30-Me moved from C-12 to C-8. Furthermore, the determined molecular formula C15H22O4 and the key 1H-1H COSY correlations with H-9 [δH 2.40 (1H, m)]/H-11 [δH 6.27 (1H, dd, J = 2.9, 10.2 Hz)], H-11/H-12 [δH 5.59 (1H, d, J = 10.2 Hz)] and the HMBC correlations from H-30 [δH 0.94 (1H, m)] to C-8 (δC 37.5 s), C-9 (δC 46.9 d) and C-14 (δC 55.1 s), from H-11to C-9 and C-10 (δC 35.6 s) and from H-12 to C-13 (δC 140.3 s) confirmed this hypothesis. The other 1H-1HCOSY and HMBC correlations (Figure 2) also confirmed this atom connectivity. The relative configuration of compound 1 was determined to be closed to the kadindutic acid (Figure 2) [12] except for the β-oriented of C-30, and α-oriented of H-9 and C-18 by ROESY cross-peaks H-19 [δH 0.89 (3H, s)]/H-30 [δH 0.95 (3H, s)], H-9/H-18 [δH 1.02 (3H, s)]. Thus, the structure of compound 1 was assigned as shown and named kadsuricoccins B.
Compounds 1–5 were all tested for their AchE-inhibitory activity by Ellman’s Method as described before [13]. As a result, compounds 1–3 (at the concentration of 94 nM) showed moderate activity with the AChE inhibit index (AII) 68.96 ± 0.19, 57.8 ± 0.11 and 37.55 ± 0.12 % at 94 nM, respectively, compared with the negative control (AII 8.94 ± 0.09%) and positive control (tacrine with AII 79.8 ± 0.20 %, 9.4 nM) (Table 2). The LD50 of the compounds 1 and 2 were predicted as 4,000 mg/kg and 900 mg/kg, with toxicity categorized into classes 5 and 4, respectively. Other ADMET properties were also predicted and analyzed (see supporting information).

3. Experimental

3.1. General

Optical rotations were measured on an MCP 5100 polarimeter (Anton Paar, Graz, Austria), UV spectra were acquired on a UV-250 spectrometer (Shimadzu, Kyoto, Japan) and IR spectra were measured on a Nicolet 380 spectrometer (Thermo, Berkeley, CA, USA) with KBr pellets. 1D and 2D NMR spectra were obtained using an AV-500 instrument (Bruker, Billerica, MA, USA) with TMS as an internal standard, and ESIMS and HRESIMS were recorded with an Autospec Premier spectrometer (Waters, Milford, MA, USA) or a Micromass Autospec-Uitima-TOF (Waters, Milford, MA, USA). The column chromatography (CC) was performed on ODS (40–70 μM, Fuji Silysia Chemical Ltd., Nagoya, Japan), Silica gel (200–300 mesh, Qingdao Marine Chemical Inc., Qingdao, China), and Sephadex LH-20 (GE Healthcare Bio-Sciences AB, Uppsala, Sweden). Fractions were color detected by TLC and heating after being soaked with 10% H2SO4 in ethanol (EtOH).
The toxicity and other ADMET properties (Druglikeness, Pharmacokinetics, Lipophilicity, etc.) of the compounds were also analyzed using the SwissADME (http://www.swissadme.ch/index.php) and ProTox-II—Prediction of Toxicity of Chemicals (http://tox.charite.de/protox_II/).

3.2. Plant Material

The stems of Heilaohu [Kadsura coccinea (Lem.) A. C. Smith.] were collected in Changjiang Hainan Province (E 109° 10′ 0.53′′, N 19° 3′ 39.7′′), People′s Republic of China, in May 2017. The voucher specimen (HUANG00012) identified by Prof. Dr. Jun Wang (Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agriculture Sciences) was deposited at the Hainan Key Laboratory for Research and Development of Natural Products from Li Folk Medicine, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agriculture Sciences, Haikou, People’s Republic of China.

3.3. Extraction and Isolation

The air-dried roots of K. coccinea (35 kg) were powdered and extracted with 95% EtOH for two weeks (3 × 100 L). The combined EtOH solution was concentrated with a rotary evaporator and followed by suspension in 2.5 L of water, then extracted successively with petroleum ether extract (3 × 5 L). The petroleum ether extract (305 g) was first subjected to silica gel (φ 16 × 150 cm) CC eluted with petroleum ether/ethyl acetate (EtOAc) (from 50:1 to 1:1, v/v) to obtain fractions A–C. Fraction B (36) was chromatographed repeatedly over an MCI with MeOH and acetone, an ODS (φ 4 × 18 cm) with MeOH/H2O (gradient elution with 30, 40, 50, 60, 70, 80 and 90%, each 500 mL), and Sephadex LH-20 CC (MeOH/CHCl3 1:1 as solvent) to yield cycloartenone (4) (2.0 mg), and 24-methyl-8-lanoten-3-one (5) (3.0 mg), respectively. Fraction C (15 g) was then subjected to CC over silica gel (φ 6 × 45 cm) eluted with petroleum ether/acetone (from 5:1 to 2:1, v/v) to give four fractions C1–C3. Fractions C1 (1.5 g) was chromatographed repeatedly over an ODS (φ 4 × 18 cm) with MeOH/H2O (gradient elution with 30, 40, 50, 60, 70, 80 and 90%, each 500 mL) and Sephadex LH-20 CC (MeOH/CHCl3 1:1 as solvent) to yield auranticanol C (4) (1.5 mg). Fraction C2 (5.6) was chromatographed repeatedly over an ODS (φ 4 × 18 cm) with MeOH/H2O (gradient elution with 20, 30, 40, 50, 60, 70, 80 and 90%, each 500 mL) to obtain fractions C2a–C2d. Fractions C2a–C2d were chromatographed repeatedly over Sephadex LH-20 CC, using MeOH/CHCl3 1:1 as solvent to yield 1 (1.9 mg), 2 (7.0 mg) and 3 (3.8 mg), respectively.

3.3.1. Kadsuricoccin A (1)

Colorless, amorphous powder; [α ] D 18.2 +23.8 (c 0.02, MeOH); UV (MeOH) λmax (logε) 294 (2.04), 255 (2.36), 215 (2.23), 209 (1.68) nm; IR (KBr) νmax 2963, 2935, 2924, 1712, 1691, 1623, 1344, 1321, 1302; 1H and 13C-NMR data see Table 1; ESIMS positive m/z [M + Na]+ 381(50); HRESIMS m/z [M + Na]+ 381.2503 (calcd for C23H34O3Na, 381.2508).

3.3.2. Kadsuricoccin B (2)

Colorless oil; [α ] D 17.0 −6.14 (c 0.10, CHCl3); UV (MeOH) λmax (logε) 286 (0.59), 254 (2.10), 218 (2.09) nm; IR (KBr) νmax 3388, 2958, 1705, 1457, 1380, 1243, 1099, 1027, 798 cm−1; 1H and 13C-NMR data see Table 1; ESIMS positive m/z [M + Na]+ 475 (40); HRESIMS m/z [M + Na]+ 475.3208 (calcd for C30H44O3Na+, 475.3183).

3.4. Acetylcholinesterase (AchE)-Inhibitory Bioassay

The AchE-inhibitory activity of the compounds was tested as described by Ellman’s Method in the literature [13,14]. The mixed reaction solution contained test compound soln. (100 μM in dimethyl sulfoxide (DMSO), 10 μL, tacrine as a positive control, 10 μM in DMSO, 10 μL,), phosphate buffer (pH 8.0 (slightly alkali), 1010 μL), and AchE soln. (0.04 U/100 μL, 40 μL). After being incubated for 20 min (at 30 °C), the reaction was initiated by the addition of DTNB [5,5′-dithiobis (2-nitrobenzoic acid), 6.25 mM] 20 μL and acetylthiocholine 20 μL.
The acetylthiocholine hydrolysis reaction was monitored at 405 nm after 30 min later. All the reactions were performed in triplicate. The AChE inhibit index (AII) was calculated according to the equation: %inhibition = (ES)/E × 100 (S, the activity of enzyme with test compound; E, activity of the enzyme without test compound).

4. Conclusions

The skeleton diversity of triterpenoids in the Schisandraceae family makes the phytochemisty and organic synthesis chemistry of this family of great interest to our research field [5,15]. An octanordammarane (a kind of octanary nor-triterpenoid) isolated from this genus firstly showed its accessibility from the Schisandraceae plant, whilst other compounds isolated from Kadsura coccinea indicated the probability of biosynthesis as other Kadsura plants [16]. Furthermore, the bioactivity evaluation assay showed that kadsuricoccins A and B have moderate AChE inhibitory activities with predicted lower toxicity as some pentacyclic triterpenoids [17], while the AChE was an important target for Alzheimer’s Disease (AD) [18] and myasthenia gravis [19]. With that, these two new compounds were found that they may be used as a health supplement.

Supplementary Materials

The following are available online.

Author Contributions

Conceptualization, S.Z. Huang and H.F.D.; Methodology, S.Z.H.; Validation, W.L.M. and H.F.D.; Formal Analysis, L.P.D. and H.W.; Investigation, X.X.; Resources, S.Z.H.; Data Curation, H.W.; Writing-Original Draft Preparation, S.Z.H.; Writing-Review & Editing, S.Z.H.; Visualization, S.Z.H.; Supervision, H.F.D.; Project Administration, S.Z.H. and H.F.D.; Funding Acquisition, S.Z.H. and H.F.D.

Funding

This research was funded by [China Agriculture Research System] grant number [CARS-21], [Financial Fund of the Ministry of Agriculture and Rural Affairs, P. R. of China] grant number [NFZX2018], and [Hainan Province Key Research and Development Program] grant number [ZDYF2019029].

Acknowledgments

The authors pay honor to respected teacher Jun Zhou and H.D. Sun (Kunming Institute of Botany, C. A. S.). The authors thank Y. L. Huang (dept. of clinical development. Pfizer (China). Shanghai) for initial proofreading of this paper.

Conflicts of Interest

All the authors of this manuscript state that they have no conflict of interest.

References

  1. Shahidi, F.; Ho, C.T. Flavor Chemistry of Ethnic Foods; Springer: Boston, MA, USA, 1999; pp. 1–4. [Google Scholar]
  2. Dai, H.F.; Guo, Z.K. Compilation of Proved Folk Recipes from the Li Nationlity; Science and technology of China press: Beijing, China, 2014; p. 576. [Google Scholar]
  3. Dai, H.F.; Mei, W.L. The Records of Li Folk Medicine; Science and technology of China press: Beijing, China, 2007; Volume 1, p. 301. [Google Scholar]
  4. Liu, Y.B.; Yang, Y.P.; Tasneem, S.; Hussain, N.; Daniyal, M.; Yuan, H.W.; Xie, Q.L.; Jian, Y.Q.; Li, B.; Chen, S.H.; et al. Lignans from Tujia Ethnomedicine Heilaohu: Chemical Characterization and Evaluation of Their Cytotoxicity and Antioxidant Activities. Molecules 2018, 23, 2147. [Google Scholar] [CrossRef] [PubMed]
  5. Liang, C.Q.; Shi, Y.M.; Li, X.Y.; Luo, R.H.; Li, Y.; Zheng, Y.T.; Zhang, H.B.; Xiao, W.L.; Sun, H.D. Kadcotriones A-C: Tricyclic triterpenoids from Kadsura coccinea. J. Nat. Prod. 2013, 76, 2350–2354. [Google Scholar] [CrossRef] [PubMed]
  6. Hu, Z.X.; Shi, Y.M.; Wang, W.G.; Tang, J.W.; Zhou, M.; Du, X.; Zhang, Y.H.; Pu, J.X.; Sun, H.D. Structural characterization of kadcoccinin A: A sesquiterpenoid with a tricyclo[4.4.0.03,10]decane scaffold from Kadsura coccinea. Org. Lett. 2016, 18, 2284–2287. [Google Scholar] [CrossRef] [PubMed]
  7. Fang, L.Z.; Xie, C.F.; Wang, H.; Jin, D.Q.; Xu, J.; Guo, Y.Q.; Ma, Y.Q. Lignans from the roots of Kadsura coccinea and their inhibitory activities on LPS-induced NO production. Phytochem. Lett. 2014, 9, 158–162. [Google Scholar] [CrossRef]
  8. Bui, D.A.; Vu, M.K.; Nguyen, H.D.; Nguyen, L.T.T.; Dang, S.V.; Nguyen, L.H.D. A protostane and two lanostanes from the bark of Garcinia ferrea. Phytochemistry Lett. 2014, 10, 123–126. [Google Scholar] [CrossRef]
  9. Ragasa, C.V.; Jorvina, K.; Rideout, J. Antimicrobial compounds from Artocarpus heterophyllus. Philipp. J. Sci. 2004, 133, 97–101. [Google Scholar]
  10. Yamashita, M.; Naora, M.; Murae, T.; Tsuyuki, T.; Takahashi, T. Synthesis of a 24-epimeric mixture of 4α, 14α, 24-trimethyl-9(11)-cholesten-3-one. B. Chem. Soc. Jap. 1987, 60, 1383–1389. [Google Scholar] [CrossRef]
  11. Provan, G.J.; Gray, A.I.; Waterman, P.G. Mansumbinane derivatives from stem bark of Commiphora kua. Phytochemistry 1992, 31, 2065–2068. [Google Scholar] [CrossRef]
  12. Ma, W.; Ma, X.; Huang, H.; Zhou, P.; Chen, D. Dibenzocyclooctane lignans from the stems of kadsura induta and their antiviral effect on hepatitis b virus. Chem. Biodivers. 2010, 4, 966–972. [Google Scholar] [CrossRef] [PubMed]
  13. Huang, S.Z.; Luo, H.R.; Ma, Q.Y.; Peng, H.; Dai, H.F.; Zhou, J.; Zhao, Y.X. Chemical constituents from the stems of Excoecaria acertiflia. Chem. Biodivers 2014, 11, 1406–1416. [Google Scholar] [CrossRef] [PubMed]
  14. Ellman, G.L.; Courtney, K.D.; Andres, V.; Feather-Stone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961, 7, 88–95. [Google Scholar] [CrossRef]
  15. Cao, L.; Shehla, N.; Tasneem, S.; Cao, M.; Sheng, W.; Jian, Y.; Li, B.; Peng, C.; Choudhary, M.I.; Liao, D.F. New Cadinane Sesquiterpenes from the Stems of Kadsura heteroclita. Molecules 2019, 24, 1664. [Google Scholar] [CrossRef] [PubMed]
  16. Liu, Y.B.; Yang, Y.P.; Yuan, H.W.; Li, M.J.; Qi, Y.X.; Choudhary, M.I.; Wang, W. A Review of Triterpenoids and Their Pharmacological Activities from Genus Kadsura. Digit. Chin. Med. 2018, 1, 247–258. [Google Scholar] [CrossRef]
  17. Gurovic, M.S.; Castro, M.J.; Richmond, V.; Faraoni, M.B.; Maier Marta, S.; Murray, A.P. Triterpenoids with acetylcholinesterase inhibition from Chuquiraga erinacea D. Don. subsp. erinacea (Asteraceae). Planta Med. 2009, 76, 607–610. [Google Scholar] [PubMed]
  18. Chuong, N.N.; Huong, N.T.; Hung, T.M.; Luan, T.C. Anti-Cholinesterase Activity of Lycopodium Alkaloids from Vietnamese Huperzia squarrosa (Forst.) Trevis. Molecules 2014, 19, 19172–19179. [Google Scholar] [CrossRef] [PubMed]
  19. Galdeano, C.; Coquelle, N.; Cieslikiewicz-Bouet, M.; Bartolini, M.; Pérez, B.; Clos, M.V.; Silman, I.; Jean, L.; Colletier, J.P.; Renard, P.Y. Increasing Polarity in Tacrine and Huprine Derivatives: Potent Anticholinesterase Agents for the Treatment of Myasthenia Gravis. Molecules 2018, 23, 634. [Google Scholar] [CrossRef] [PubMed]
Sample Availability: Samples of the compounds are not available from the authors.
Figure 1. The structures of compounds 15.
Figure 1. The structures of compounds 15.
Molecules 24 03628 g001
Figure 2. Key 1H-1H COSY (), HMBC (H→C), and ROESY (↔) correlations of 12.
Figure 2. Key 1H-1H COSY (), HMBC (H→C), and ROESY (↔) correlations of 12.
Molecules 24 03628 g002
Table 1. 1H (500 MHz) and 13C nuclear magnetic resonance (NMR) (125 MHz) Data of Compounds 12.
Table 1. 1H (500 MHz) and 13C nuclear magnetic resonance (NMR) (125 MHz) Data of Compounds 12.
Compound1 (in CDCl3)2 (in CDCl3)
No.δH mult. (J in Hz)δCδH mult. (J in Hz)δC
12.01 m
1.87 m
30.2 t1.71 m
2.21 m
32.1 t
22.29 m30.3 t2.87 ddd, (7.2, 12.0, 14.8)
2.21 m
33.2 t
3-174.8 s-221.6 s
4-147.0 s-47.0 s
52.18 m47.0 d2.41 s46.3 d
61.95 m
1.49 m
22.1 t1.53 dd, (7.6, 12.9)
1.34 m
19.0 t
72.08 m
1.17 m
27.3 t1.97 m
1.29 d, (6.3)
31.2 t
8-37.4 s-37.5 s
92.25 m41.2 d2.40 m46.9 d
10 37.7 s 35.6 s
112.21 m24.7 t6.27 dd, (2.9, 10.2)121.5 d
126.65 dd, (3.4, 3.6)131.4 d5.59 d, (10.2)126.6 d
13-144.1 s-140.3 s
14-48.6 s -55.1 s
151.99 m
1.54 m
26.8 t2.43 m27.8 t
162.46 m
2.28 m
36.1 t1.38 m28.6 t
17-207.1 s-138.8 s
181.18 s23.4 q1.02 s22.0 q
190.91 s17.7 q0.89 s23.9 q
204.96 s
4.84 s
113.4 t2.66 m31.7 d
211.82 s26.9 q1.01 d, (7.6)19.2 q
220.94 s25.1 q1.44 m34.9 t
23/OMe 3.69 s51.7 q2.32 dd, (8.8, 16.5)28.1 t
24 5.86 t, (7.2)139.3 d
25 128.7 s
26 171.5 s
27 1.87 s19.7 q
28 1.11 s28.2 q
29 1.03 s18.3 q
30 0.95 s19.0 q
Table 2. The acetylcholinesterase (AChE) inhibit index (AII) of compounds 15 (94 nM) with the inhibition rate of this same acetylcholinesterase.
Table 2. The acetylcholinesterase (AChE) inhibit index (AII) of compounds 15 (94 nM) with the inhibition rate of this same acetylcholinesterase.
CompoundsAII (%)
168.96 ± 0.19
257.8 ± 0.11
337.75 ± 0.12
417.23 ± 0.08
525.66 ± 0.18
Blank control8.94 ± 0.09
Tacrine (positive control, 9.4 nM)79.80 ± 0.20

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