Structure-activity relationships of bergenin derivatives effect on α-glucosidase inhibition

Figures & data

Figure 1.  Chemical structures of bergenin (1) and its derivatives (2–9).

Scheme 1.  Reagents and conditions: (a) allylbromide, K₂CO₃, NaI, DMF; (b) DIAD, P(Ph)₃, RCOOH, THF; (c) 10% Pd(PPh₃)₄, 20 equiv., morpholine, THF.

Scheme 2.  Reagents and conditions: (a) DIAD, P(Ph)₃, 3,4-diallyloxy-protocatechuic acid, THF; (b) 10% Pd(PPh₃)₄, 20 equiv., morpholine, THF.

Table 1.  13C NMR spectral data for compounds 2–9 (δ in ppm).

Position	2	3	4	5	6	7	8	9
2	78.5	78.6	78.5	78.6	78.5	78.5	78.3	78.5
3	70.2	70.2	70.2	70.1	70.5	70.5	70.5	70.8
4	73.5	73.5	73.5	73.5	73.5	73.5	73.5	73.5
4a	79.6	79.6	79.6	79.6	79.5	79.6	79.5	79.5
6	163.4	163.4	163.4	163.4	163.3	163.3	163.3	163.2
6a	118.1	118.1	118.1	118.1	118.1	118.1	118.1	118.1
7	109.5	109.5	109.5	109.5	109.6	109.6	109.6	109.6
8	150.9	150.9	150.9	150.9	151.0	151.0	151.0	151.1
9	140.6	140.6	140.6	140.6	140.6	140.6	140.6	140.6
10	148.0	148.0	148.0	148.0	148.0	148.0	148.0	148.0
10a	115.8	115.8	115.8	115.8	115.7	115.8	115.7	115.7
10b	72.2	72.2	72.2	72.2	72.1	72.1	72.1	72.1
11	64.0	63.5	63.7	63.4	64.0	63.8	64.1	64.0
9-OCH3	59.7	59.7	59.7	59.8	59.7	59.7	59.7	59.7
1'	129.5	120	121.7	120.2	123.4	120.2	131.5	119.0
2'	129.2	131.6	131.4	116.4	111.2	112.6	106.9	107.0
3'	128.8	115.4	114.1	145.1	148.4	147.4	160.5	147.6
4'	133.5	162.2	163.3	150.7	153.1	151.8	105.5	141.1
5'	128.8	115.4	114.1	115.3	111.7	115.2	160.5	147.7
6'	129.2	131.6	131.4	122.0	121.6	123.7	106.9	107.0
COO	165.6	165.5	165.4	165.6	165.3	165.4	165.2	165.3
3′-OCH3					55.5	55.6	55.5	56.1
4′-OCH3			55.6		55.7
5′-OCH3							55.5	56.1

¹³C NMR spectral data were recorded at 100 MHz in DMSO-d6 using tetramethylsilane (TMS) as internal standard.

Figure 2.  Dose-dependent inhibitory effects of bergenin (1) and its derivatives (2–9). Acarbose and 1-deoxynojirimycin were used a positive control. The result represents the means of triplicate experiments.

Table 2.  Inhibition effects of bergenin (1) and bergenin derivatives (2–10) against α-glucosidase.

Compound	IC50 (µM)^a	Compound	IC50 (µM)^a
1	>300	Benzoic acid	>300
2	118.3 ± 0.7	p-Hydroxybenzoic acid	>300
3	143.2 ± 2.0	Anisic acid	>300
4	143.8 ± 2.3	Protocatechuic acid	>300
5	289.6 ± 1.4	3,4-Dimethoxybenzoic acid	>300
6	24.6 ± 0.3	Vanilic acid	>300
7	186.9 ± 2.3
8	>300	Acarbose^b	907.5 ± 2.2
9	>300	1-Deoxynojirimycin^b	278.0 ± 1.7

^aData represents means ± SD of triplicate samples.

^bThis compound was used as a positive control.

Figure 3.  Lineweaver–Burk plot (panel A) and Dixon plot (panel B) for inhibition of compound 2 (0, 75, 150 and 300 µM) on α-glucosidase activity.

Figure 4.  Lineweaver–Burk plot (panel A) and Dixon plot (panel B) for inhibition of compound 6 (0, 7.5, 15 and 30 µM) on α-glucosidase activity.

Figure 5.  Lineweaver–Burk plot (panels A and C) and Dixon plot (panels B and D) for inhibition of acarbose (0, 0.5, 1.0 and 2.0 mM) and 1-deoxynojirimycin (0, 200, 400 and 800 μM) on α-glucosidase activity.

Figure 6.  Line weaver–Burk plots for the inhibition of the hydrolysis activity of α-glucosidase by compounds 3 (0, 75 and 150 mM) (a) and 4 (0, 75, 150 and 300 mM) (b).