Quinazolinone-dihydropyrano[3,2-b]pyran hybrids as new α-glucosidase inhibitors: Design, synthesis, enzymatic inhibition, docking study and prediction of pharmacokinetic

被引：17

作者：

Sherafati, Maedeh ^{[1
]}

Mirzazadeh, Roghieh ^{[2
]}

Barzegari, Ebrahim ^{[3
]}

Mohammadi-Khanaposhtani, Maryam ^{[4
]}

Azizian, Homa ^{[5
]}

Asgari, Mohammad Sadegh ^{[6
]}

Hosseini, Samanesadat ^{[7
]}

Zabihi, Ebrahim ^{[4
]}

Mojtabavi, Somayeh ^{[8
]}

Faramarzi, Mohammad Ali ^{[8
]}

Mahdavi, Mohammad ^{[1
]}

Larijani, Bagher ^{[1
]}

Rastegar, Hossein ^{[9
]}

Hamedifar, Haleh ^{[10
]}

Hajimiri, Mir Hamed ^{[11
]}

机构：

[1] Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Endocrinol & Metab Clin Sci Inst, Tehran, Iran

[2] Pasteur Inst Iran, Dept Biochem, Tehran, Iran

[3] Kermanshah Univ Med Sci, Med Biol Res Ctr, Hlth Technol Inst, Kermanshah, Iran

[4] Babol Univ Med Sci, Cellular & Mol Biol Res Ctr, Hlth Res Inst, Babol, Iran

[5] Iran Univ Med Sci, Sch Pharm, Dept Med Chem, Tehran, Iran

[6] Iran Univ Sci & Technol, Dept Chem, Tehran, Iran

[7] Shahid Beheshti Univ Med Sci, Sch Pharm, Dept Pharmaceut Chem, Tehran, Iran

[8] Univ Tehran Med Sci, Fac Pharm, Dept Pharmaceut Biotechnol, Tehran, Iran

[9] Iranian Food & Drug Adm, Cosmet Prod Res Ctr, MOHE, Tehran, Iran

[10] Alborz Univ Med Sci, CinnaGen Med Biotechnol Res Ctr, Karaj, Iran

[11] Univ Tehran Med Sci, Nano Alvand Co, Avicenna Tech Pk, Tehran, Iran

来源：

BIOORGANIC CHEMISTRY | 2021年 / 109卷

关键词：

-Glucosidase; Quinazolinone-dihydropyrano[3; 2-b]pyran; hybrids; -Amylase; Type; 2; diabetes; Docking study; Pharmacokinetic prediction; DERIVATIVES; AGENTS;

D O I：

10.1016/j.bioorg.2021.104703

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of new quinazolinone-dihydropyrano[3,2-b]pyran derivatives 10A-L were synthesized by simple chemical reactions and were investigated for inhibitory activities against ?-glucosidase and ?-amylase. New synthesized compounds showed high ?-glucosidase inhibition effects in comparison to the standard drug acarbose and were inactive against ?-amylase. Among them, the most potent compound was compound 10L (IC50 value = 40.1 ? 0.6 ?M) with inhibitory activity around 18.75-fold more than acarboase (IC50 value = 750.0 ? 12.5 ?M). This compound was a competitive inhibitor into ?-glucosidase. Our obtained experimental results were confirmed by docking studies. Furthermore, the cytotoxicity of the most potent compounds 10L, 10G, and 10N against normal fibroblast cells and in silico druglikeness, ADME, and toxicity prediction of these compounds were also evaluated.

引用

页数：10

共 23 条

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