Pyrazole and pyrazolone derivatives as specific α-glucosidase inhibitors: in vitro combined with in silico, hemolytic and cytotoxicity studies

被引：10

作者：

Dhouib, Ines ^{[1
]}

Messaad, Mehdi ^{[2
]}

Hadjkacem, Basma ^{[3
]}

Fendri, Imen ^{[1
]}

Majdoub, Hafedh ^{[1
]}

Khemakhem, Bassem ^{[1
]}

机构：

[1] Univ Sfax, Sfax Fac Sci, Lab Plant Biotechnol, BP 1171, Sfax 3038, Tunisia

[2] Univ Sfax, Inst Superieur Biotechnol Sfax, Lab Med & Environm Chem, BP 261, Sfax 3000, Tunisia

[3] Univ Sfax Tunisia, Ctr Biotechnol Sfax, Lab Microbial Enzymat Biotechnol & Biomol LBMEB, BP 1177, Sfax 3018, Tunisia

来源：

JOURNAL OF MOLECULAR STRUCTURE | 2023年 / 1294卷

关键词：

Postprandial hyperglycemia; Metabolism; Pyrazole; Pyrazolone; In silico study; alpha-glucosidase; CRYSTAL-STRUCTURE; AMYLASE;

D O I：

10.1016/j.molstruc.2023.136331

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

Pyrazole and pyrazolone derivatives have the potential to be promising anti-diabetic drugs. In this work, we evaluate the inhibitory effect on alpha-amylase and alpha-glucosidase of pyrazole and pyrazolones via in vitro study using acarbose as a positive control. The results showed that 5-methyl-4-[(4-methylphenyl)sulfanyl]-1,2-dihydro-3H-pyrazol-3-one (Compound 3), 3,5,5-trimethyl-1-[(4-methylphenyl)sulfonyl]- 4,5-dihydro-1H-pyrazole (Compound 4) and acarbose inhibit alpha-amylase with IC50 of 1.95 +/- 0.098 mg/mL, 0.08 +/- 0.004 mg/mL, and 0.15 +/- 0.008 mg/mL (p < 0.05), respectively. The 3,4-dimethylpyrano [2,3-c]pyrazol-6(2H)-one (Compound 1) has no inhibitory effect of alpha-amylase. The compounds 3 and 4 inhibit alpha-glucosidase with an IC50 value of 1.55 +/- 0.078 mg/mL and 0.36 +/- 0.018 mg/mL (p < 0.05), respectively while compound 1 and acarbose have a comparable inhibition against alpha-glucosidase with an IC50 value of 0.1 +/- 0.005 mg/mL, and 0.125 +/- 0.006 mg/mL (p < 0.05), respectively. The in silico study confirmed the specificity of this compound with a difference in the binding energy and number of bonds in the case of alpha-glucosidase. In addition, the cytotoxicity and the hemolytic studies confirmed the potential of compound 1 as a safe and specific anti-postprandial hyperglycemia drug.

引用

页数：9

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