New thiosemicarbazide-1,2,3-triazole hybrids as potent α-glucosidase inhibitors: Design, synthesis, and biological evaluation

被引：30

作者：

Bakherad, Zohreh ^{[1
,2
]}

Mohammadi-Khanaposhtani, Maryam ^{[3
]}

Sadeghi-Aliabadi, Hojjat ^{[1
]}

Rezaei, Sepideh ^{[4
]}

Fassihi, Afshin ^{[1
]}

Bakherad, Mohammad ^{[5
]}

Rastegar, Hossein ^{[2
]}

Biglar, Mahmood ^{[6
]}

Saghaie, Lotfollah ^{[1
]}

Larijani, Bagher ^{[6
]}

Mahdavi, Mohammad ^{[6
]}

机构：

[1] Isfahan Univ Med Sci, Sch Pharm & Pharmaceut Sci, Dept Med Chem, Esfahan 8174673461, Iran

[2] MOHE, Food & Drug Adm, Food & Drug Res Inst, Tehran, Iran

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

[4] Tabriz Univ Med Sci, Sch Pharm, Tabriz, Iran

[5] Shahrood Univ Technol, Sch Chem, Shahrood, Iran

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

来源：

JOURNAL OF MOLECULAR STRUCTURE | 2019年 / 1192卷

关键词：

alpha-Glucosidase inhibitor; Molecular docking; Thiosemicarbazide; 1,2,3-Triazole; IN-VITRO; MOLECULAR DOCKING; THIOSEMICARBAZONE DERIVATIVES; ANTICONVULSANT ACTIVITY; EFFICIENT SYNTHESIS; ANTITUMOR-ACTIVITY; ANTIBACTERIAL; ANTIFUNGAL; THIOUREA; 1,2,3-TRIAZOLES;

D O I：

10.1016/j.molstruc.2019.04.082

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：

A new series of thiosemicarbazide-1,2,3-triazole hybrids 10a-o has been synthesized, characterized by H-1 NMR, C-13 NMR, and screened for their in vitro alpha-glucosidase inhibitory activity. All of the synthesized compounds displayed excellent alpha-glucosidase inhibitory activity with IC50 values in the range of 75.0 +/- 0.5 to 253.0 +/- 0.5 mu M, as compared to the standard drug acarbose (IC50 = 750.0 +/- 1.5 mu M). Among the synthesized compounds, compound 10h (IC50 = 75.0 +/- 0.5) with 4-methoxy group at phenyl part of thiosemicarbazide moiety and 2,6-dichloro substituents at benzyl moiety was found to be the most potent compound. Kinetic analysis revealed that compound 10h is a competitive inhibitor for alpha-glucosidase. Docking study of compound 10h in the active site of alpha-glucosidase showed that this compound interacted with residues His239, His279, Glu304, Gly306, and Arg312. (C) 2019 Elsevier B.V. All rights reserved.

引用

页码：192 / 200

页数：9

共 34 条

[1] Thiourea derivatives incorporating a hippuric acid moiety: Synthesis and evaluation of antibacterial and antifungal activities [J].