Synthesis of Bis-indolylmethane sulfonohydrazides derivatives as potent α-Glucosidase inhibitors

被引：55

作者：

Gollapalli, Mohammed ^{[1
]}

Taha, Muhammad ^{[2
,3
]}

Ullah, Hayat

Nawaz, Muhammad ^{[4
]}

AlMuqarrabun, Laode Muhammad Ramadhan ^{[5
,6
]}

Rahim, Fazal ^{[3
]}

Qureshi, Faiza ^{[4
,7
]}

Mosaddik, Ashik ^{[2
]}

Ahmat, Norizan ^{[5
,6
]}

Khan, Khalid Mohammed ^{[2
,8
]}

机构：

[1] Imam Abdulrahman Bin Faisal Univ, CCSIT, Dept Comp Informat Syst, POB 1982, Dammam 31441, Saudi Arabia

[2] Imam Abdulrahman Bin Faisal Univ, IRMC, Dept Clin Pharm, POB 1982, Dammam 31441, Saudi Arabia

[3] Hazara Univ, Dept Chem, Mansehra 21300, Pakistan

[4] Imam Abdulrahman Bin Faisal Univ, IRMC, Dept Nanomed Res, POB 1982, Dammam 31441, Saudi Arabia

[5] Univ Teknol MARA UiTM, Atta Ur Rahman Inst Nat Prod Discovery, Puncak Alam Campus, Bandar Puncak Alam 42300, Selangor, Malaysia

[6] Univ Teknol MARA UiTM, Fac Appl Sci, Shah Alam 40450, Selangor, Malaysia

[7] Imam Abdulrahman Bin Faisal Univ, Deanship Sci Res, POB 1982, Dammam 31441, Saudi Arabia

[8] Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan

来源：

BIOORGANIC CHEMISTRY | 2018年 / 80卷

关键词：

Synthesis; Bis-indolylmethane; Sulfonohydrazides; alpha-glucosidase activity; SAR; Molecular docking; MOLECULAR DOCKING; DIABETES-MELLITUS; VIBRINDOLE-A; BIOLOGICAL EVALUATION; OXINDOLE DERIVATIVES; BETA-GLUCURONIDASE; SCHIFF-BASES; ANALOGS; BIS(INDOLYL)METHANES; DISCOVERY;

D O I：

10.1016/j.bioorg.2018.06.001

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：

In search of better alpha-glucosidase inhibitors, a series of bis-indolylmethane sulfonohydrazides derivatives (1-14) were synthesized and evaluated for their alpha-glucosidase inhibitory potential. All derivatives exhibited outstanding alpha-glucosidase inhibition with IC50 values ranging between 0.10 +/- 0.05 to 5.1 +/- 0.05 mu M when compared with standard drug acarbose having IC50 value 856.28 +/- 3.15 mu M. Among the series, analog 7 (0.10 +/- 0.05 mu M) with tri-chloro substitution on phenyl ring was identified as the most potent inhibitor of alpha-glucosidase ( similar to 8500 times). The structure activity relationship has been also established. Molecular docking studies were also performed to help understand the binding interaction of the most active analogs with receptors. From the docking studies, it was observed that all the active bis-indolylmethane sulfonohydrazides derivatives showed considerable binding interactions within the active site (acarbose inhibition site) of alpha-glucosidase. We also evaluated toxicity of all derivatives and found none of them are toxic.

引用

页码：112 / 120

页数：9

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