α-Glucosidase Inhibition Research of Derivatives Based on 2β-Acetoxyferruginol Scaffold Excluding Acetic Acid Group

doi:10.6023/cjoc202307027

Chinese Journal of Organic Chemistry ›› 2024, Vol. 44 ›› Issue (2): 613-621.DOI: 10.6023/cjoc202307027 Previous Articles Next Articles

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2β-Acetoxyferruginol去醋酸基骨架衍生物抑制α-葡萄糖苷酶活性研究

吴思敏^a, 唐嘉欣^b, 周于佳^c, 徐学涛^a^,^*(), 张昊星^b^,^*(), 王少华^c^,^*()

a 五邑大学生物科技与大健康学院广东江门 529020
b 深圳大学生命与海洋科学学院广东深圳 518060
c 兰州大学药学院兰州 730000

收稿日期:2023-07-31 修回日期:2023-10-10 发布日期:2023-10-23
作者简介:
^† 共同第一作者
基金资助:
广东省教育厅基金(2021KCXTD044); 广东省教育厅基金(2021KTSCX135)

α-Glucosidase Inhibition Research of Derivatives Based on 2β-Acetoxyferruginol Scaffold Excluding Acetic Acid Group

Simin Wu^a, Jiaxin Tang^b, Yujia Zhou^c, Xuetao Xu^a(), Haoxing Zhang^b(), Shaohua Wang^c()

a School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, Guangdong 529020
b College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong 518060
c School of Pharmacy, Lanzhou University, Lanzhou 730000

Received:2023-07-31 Revised:2023-10-10 Published:2023-10-23
Contact: * E-mail: wyuchemxxt@126.com; zhang.haoxing@szu.edu.cn; wangshh@lzu.edu.cn
About author:
^† These authors contributed equally to this work.
Supported by:
Funds of Department of Education of Guangdong Province(2021KCXTD044); Funds of Department of Education of Guangdong Province(2021KTSCX135)

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Abstract

In this study, a series derivatives based on 2β-acetoxyferruginol scaffold excluding acetic acid group (1~24) were synthesized and their inhibitory activities on α-glucosidase were determined. The results showed that all compounds 1~24 had good α-glucosidase inhibitory activities. Among them, (3R,4aS,10aS)-6-hydroxy-1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octahy- drophenanthren-3-yl 4-(trifluoromethyl)benzoate (15) had the strongest inhibitory activity [IC₅₀=(23.91±2.34) μmol/L], about 23.6-fold more active than acarbose. The structure activity relationship analysis showed that the introduction of trifluoromethyl was more conducive to enhance its activity. The kinetic results showed that compound 15 was a reversible and non competitive α-glucosidase inhibitor. The 3D fluorescence results indicated that the binding of α-glucosidase with compound 15 could change the conformation of α-glucosidase. The molecular docking results showed that compound 15 made hydrogen bonds with Asp68, Arg312, and Tyr313, and formed hydrophobic interactions with Phe177 and Phe300.

Key words: 2β-acetoxyferruginol, α-glucosidase, 3D fluorescence, molecular docking

Cite this article

Simin Wu, Jiaxin Tang, Yujia Zhou, Xuetao Xu, Haoxing Zhang, Shaohua Wang. α-Glucosidase Inhibition Research of Derivatives Based on 2β-Acetoxyferruginol Scaffold Excluding Acetic Acid Group[J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 613-621.

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Fig. & Tab. 6

References 31

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Compd.	R	Inhibition rate/% at 32 μmol/L	IC₅₀/(μmol•L^—1)
1	1-Naphthalene	53.2	28.83±1.41
2	2-Naphthalene	50.8	31.15±1.32
3	2-Methoxy	8.9	—
4	3-Methoxy	31.8	—
5	4-Methoxy	34.3	—
6	3,4-Methoxy	30.6	—
7	2-Bromine	47.5	—
8	3-Bromine	30.2	—
9	4-Bromine	53.6	26.64±1.73
10	2-Methyl	43.6	—
11	3-Methyl	43.9	—
12	4-Methyl	32.8	—
13	2-Trifluoromethyl	37.7	—
14	3-Trifluoromethyl	37.2	—
15	4-Trifluoromethyl	58.3	23.91±2.34
16	3,5-Trifluoromethyl	30.6	—
17	3-Cyan	44.3	—
18	4-Cyan	57.8	26.92±1.91
19	2-Fluorine	50.1	31.75±1.86
20	3-Fluorine	45.8	—
21	4-Fluorine	55.8	26.62±1.17
22	2-Chlorine	38.5	—
23	3-Chlorine	40.7	—
24	4-Chlorine	42.9	—
阿卡波糖			564.28±4.68

Compd.	R	Inhibition rate/% at 32 μmol/L	IC₅₀/(μmol•L^—1)
1	1-Naphthalene	53.2	28.83±1.41
2	2-Naphthalene	50.8	31.15±1.32
3	2-Methoxy	8.9	—
4	3-Methoxy	31.8	—
5	4-Methoxy	34.3	—
6	3,4-Methoxy	30.6	—
7	2-Bromine	47.5	—
8	3-Bromine	30.2	—
9	4-Bromine	53.6	26.64±1.73
10	2-Methyl	43.6	—
11	3-Methyl	43.9	—
12	4-Methyl	32.8	—
13	2-Trifluoromethyl	37.7	—
14	3-Trifluoromethyl	37.2	—
15	4-Trifluoromethyl	58.3	23.91±2.34
16	3,5-Trifluoromethyl	30.6	—
17	3-Cyan	44.3	—
18	4-Cyan	57.8	26.92±1.91
19	2-Fluorine	50.1	31.75±1.86
20	3-Fluorine	45.8	—
21	4-Fluorine	55.8	26.62±1.17
22	2-Chlorine	38.5	—
23	3-Chlorine	40.7	—
24	4-Chlorine	42.9	—
阿卡波糖			564.28±4.68

2β-Acetoxyferruginol去醋酸基骨架衍生物抑制α-葡萄糖苷酶活性研究

α-Glucosidase Inhibition Research of Derivatives Based on 2β-Acetoxyferruginol Scaffold Excluding Acetic Acid Group

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