Isoquinoline alkaloids isolated from Glaucium corniculatum var. corniculatum and Glaucium grandiflorum subsp. refractum var. torquatum with bioactivity studies

Figures & data

Figure 1. Images of some Glaucium species. A: Glaucium grandiflorum subsp. refractum var. torquatum (Aslan 2012); B: Glaucium corniculatum var. corniculatum.

Figure 2. Structures of the compounds isolated from G. grandiflorum subsp. refractum var. torquatum (Aslan 2012) and G. corniculatum var. corniculatum.

Table 1. Amounts of the isolated alkaloids from Glaucium species.

Glaucium species	Alkaloids	Amounts of alkaloids (mg)
Glaucium grandiflorum Boiss. & Huet. subsp. refractum var. torquatum Cullen (Aslan 2012).	Corydine (1)	12
	Isocorydine (2)	8
	Glauciumoline (3)	10
	Protopine (5)	15
Glaucium corniculatum (L.) Rud. var. corniculatum	Glauciumoline (3)	16
	Glaucine (4)	45
	N-Methyl canadine (6)	30
	trans-Protopinium (7)	20
	cis-Protopinium (8)	27

Table 2. ¹H and ¹³C NMR data of protopine alkaloids glauciumoline (3), protopine (5), N-methyl canadine (6), trans-protopinium (7) and cis-protopinium (8).

Carbon	3 (CD3OD)		5 (CDCl3)		6 (CD3OD)		7 (CD3OD)		8 (CD3OD)
	δH	δC	δH	δC	δH	δC	δH	δC	δH	δC
1	6.98 s, 1H	107.30	6.93 s, 1H	110.52	6.88 s, 1H	113.14	7.11 s, 1H	107.56	7.05 s, 1H	107.11
2	–	146.47	–	148.84	–	145.84	–	148.92	–	150.71
3	–	151.29	–	150.82	–	150.31	–	150.51	–	149.29
4	6.68 s, 1H	109.03	6.63 s, 1H	112.78	7.16 s, 1H	110.78	6.76 s, 1H	110.07	6.69 s, 1H	109.73
4a	–	134.07	–	135.20	–	125.01	–	n.d.	–	124.08
5	3.13 m, 1H 2.94 m, 1H	29.34	n.d.	32.01	3.38 m, 2H	25.15	3.20 bd, 2H	27.00	3.09 m, 1H 3.32 bd, 1H	25.20
6	3.20 m, 1H 2.77 m, 1H	55.09	3.90 m, 2H	54.21	3.62 m, 1H 3.68 m, 1H	55.72	3.45 bd, 2H	55.99	4.48 d (J = 16.0 Hz), 2H	56.37
8	4.08 m, 1H 3.98 m, 1H	51.79	3.91 m, 2H	59.97	4.62 s, 1H 3.87 s, 1H	56.19	3.62 m, 2H	55.47	3.80 m, 1H 3.53 m, 1H	55.39
8a	–	n. d.	–	130.70	–	124.49	–	n.d.	–	126.05
9	–	151.29	–	148.73	–	148.05	–	148.00	–	148.10
10	–	146.39	–	148.67	–	152.07	–	146.14	–	145.77
11	6.96 d (J = 7.8 Hz), 1H	111.37	6.70 d (J = 7.9 Hz), 1H	109.77	6.87 d (J = 7.8 Hz), 1H	109.88	6.84 d (J = 8.0 Hz), 1H	109.53	6.78 d, (J = 8.2 Hz), 1H	110.01
12	7.04 d (J = 7.8 Hz), 1H	126.58	6.66 d (J = 7.9 Hz), 1H	127.28	6.84 d (J = 7.8 Hz), 1H	123.76	6.80 d (J = 8.0 Hz), 1H	124.21	6.73 d, (J = 7.9 Hz), 1H	123.68
12a	–	n.d.	–	130.80	–	124.49	–	n.d.	–	124.08
13	3.32 bs, 1H	48.92	3.63 bs, 2H	32.35	3.45 m, 1H 3.19 bd, 1H	31.95	3.88 bs, 2H	31.50	1.20, 2H	30.91
14	3.92 m, 1H	59.66	–	n.d.	3.97 m, 1H	55.72	–	n.d.	–	n.d.
14a	–	134.07	–	129.10	–	125.31	–	n.d.	–	110.50
N-CH3	2.23 s, 3H	39.65	2.13 s, 3H	44.50	3.05 s, 3H	43.55	2.88 s, 3H	43.29	2.96 s, 3H	43.70
2,3-O-CH2-O	5.95 s, 2H	101.26	5.95 s, 2H	103.68	6.03 s, 2H	103.51	6.01 s, 2H	103.34	5.91 s, 2H	103.38
9,10-O-CH2-O	–	–	5.93 s, 2H	103.93	–	–	5.99 s, 2H	103.26	5.94 s, 2H	103.58
9-OCH3	3.83 s, 3H	54.84	–	–	3.88 s, 3H	56.65	–	–	–	–
10-OCH3	3.78 s, 3H	59.66	–	–	3.86 s, 3H	56.94	–	–	–	–

n.d.: not detected.

Figure 3. HMBC correlations of the glauciumoline (3).

Figure 4. Trolox Equivalent Antioxidant Capacities of the extracts calculated with respect to the ABTS and CUPRAC methods. G. grandiflorum subsp. refractum var. torquatum (Aslan 2012) tertiary amine extract: GG TAE; G. corniculatum var. corniculatum tertiary amine extract: GC TAE; G. grandiflorum subsp. refractum var. torquatum (Aslan 2012) tertiary amine extract: GG TAE; G. grandiflorum subsp. refractum var. torquatum (Aslan 2012) quaternary amine extract: GG QAE. Test results for each extract shown with superscript capital letters (A–C) indicate significant differences (p<0.05) according to the Fisher test.

Figure 5. β-Carotene lipid peroxidation inhibition results of the Glaucium extracts. G. grandiflorum var. torquatum tertiary amine extract: GG TAE; G. grandiflorum subsp. refractumvar. torquatum (Aslan 2012) quaternary amine extract: GG QAE; G. corniculatum var. corniculatum tertiary amine extract: GC TAE; G. corniculatum subsp. refractum var. corniculatum (Aslan 2012) quaternary amine extract: GC QAE; Test results for each extract shown with superscript capital letters (A–D) indicate significant differences (p<0.05) according to the Fisher test.

Figure 6. Lipid peroxidation inhibition results of the alkaloids from the Glaucium species. BHT, BHA, and α -Tocopherol were used as positive standards). Test results for each compound shown with superscript capital letters (A–E) indicate significant differences (p<0.001) according to the Fisher test.

Figure 7. Anticholinesterase activity results of the G. grandiflorum subsp. refractum var. torquatum (Aslan 2012) extracts. GG TAE: Tertiary amine extract; GG QAE: Quaternary amine extract. Test results for each extract shown with superscript capital letters (A–E) indicate significant differences (p<0.05) according to the Fisher test.

Figure 8. Anticholinesterase inhibition activity results of the G. corniculatum var. corniculatum extracts. GC TAE: Tertiary amine extract; GC QAE: Quaternary amine extract. Test results for each extract shown with superscript capital letters (A–E) indicate significant differences (p<0.01) according to the Fisher test.

Figure 9. Acetylcholinesterase (AChE) inhibition activity results of isolated alkaloids from the Glaucium species. Statistical analysis was not performed because the test substances were not active.

Figure 10. Butyrylcholinesterase (BChE) inhibitory activity results of the isolated alkaloids from the Glaucium species. Statistical analysis was not performed because the test substances were not active.

Table 3. ¹H and ¹³C NMR data of aporphine alkaloids corydine (1), isocorydine (2) and glaucine (4).

Carbon	1 (CDCl3)		2 (CDCl3)		4 (CD3OD)
	δH	δC	δH	δC	δH	δC
1	–	151.70	–	146.57	–	146.07
1a	–	129.83	–	121.83	–	126.84
1b	–	129.85	–	127.00	–	128.15
2	–	140.78	–	154.86	–	154.08
3	6.70 s, 1H	111.29	6.71 s, 1H	113.80	6.64 s, 1H	112.14
3a	–	120.30	–	127.68	–	129.66
4	2.54 m, 2H	29.91	2.76 m, 2H	25.34	2.58 m, 1H 3.05 dd, 1H (J = 4.1; 13.5 Hz)	29.27
5	3.05 dd, (J = 12.9; 3.6 Hz), 2H	52.88	3.13 d, (J = 12.3 Hz), 2H	34.56	2.68 (J = 15.3; 3.0 Hz), 1H 3.09 dd (J = 4.7; 8.8 Hz), 1H	54.25
6a	3.24 m, 1H	62.60	3.30 m, 1H	58.75	3.12 m, 1H	56.51
7	2.72 bd, (J = 2.3; 16.4 Hz), 2H	35.80	2.76 m, 2H	27.52	2.45 t (J = 12.9 Hz), 1H 3.63 m, 1H	43.67
7a	–	126.20	–	127.37	–	130.35
8	6.82 d (J = 8.8 Hz), 1H	119.26	6.90 d, (J = 8.2 Hz), 1H	113.99	6.82 s, 1H	112.84
9	6.85 d (J = 8.2 Hz), 1H	111.36	7.12 d, (J = 8.2 Hz), 1H	127.69	–	150.12
10	–	144.26	–	154.86	–	149.25
11	–	15	–	146.57	7.89 s, 1H	113.63
11a	–	126.20	–	122.14	–	125.77
N-CH3	2.57 s, 3H	43.90	2.72 s, 3H	46.00	2.55 s, 3H	43.84
1-OCH3	–	–	3.91 s, 3H	58.82	3.78 s, 3H	56.60
2-OCH3	3.70 s, 3H	62.31	3.92 s, 3H	58.72	3.76 s, 3H	56.84
9-OCH3	–	–	–	–	3.75 s, 3H	60.67
10-OCH3	3.90 s, 3H	56.13	3.74 s, 3H	64.74	3.53 s, 3H	63.99
11-OCH3	3.91 s, 3H	56.39	–	–	–	–
O-CH2-O	–	–	–	–	–	–

n.d.: not detected.

Aslan S. 2012. Glaucium Mill. In: Guner A, Aslan S, Ekim T, Vural M, Babaç MT, editors. List of plants of Turkey (vascular plants). İstanbul: İstanbul Nezahat Gökyiğit Botanical Garden Publications; p. 663–664.

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