Evaluation of 2-indolcarbohydrazones as potent α-glucosidase inhibitors, in silico studies and DFT based stereochemical predictions

被引：45

作者：

Taha, Muhammad ^{[1
,2
]}

Ismail, Nor Hadiani ^{[1
,2
]}

Javaid, Kulsoom ^{[3
]}

Imran, Syahrul ^{[1
,2
]}

Anouar, El Hassane ^{[4
]}

Wadood, Abdul ^{[5
]}

Atia-tul-Wahab ^{[6
]}

Ali, Muhammad ^{[7
]}

Khan, Khalid Mohammed ^{[3
]}

Saad, Syed Muhammad ^{[3
]}

Rahim, Fazal ^{[8
]}

Choudhary, M. Iqbal ^{[1
,3
,6
,9
]}

机构：

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

[2] Fac Appl Sci UiTM, Shah Alam 40450, Selangor, Malaysia

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

[4] Sattam bin Abdulaziz Univ, Dept Chem, Coll Sci & Humanities, Al Kharj 11942, Saudi Arabia

[5] Abdul Wali Khan Univ Mardan, Dept Biohemistry, Mardan 23200, Pakistan

[6] Univ Karachi, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan

[7] COMSATS Inst Informat Technol, Ctr Adv Drug Res, Abbottabad 22060, Kpk, Pakistan

[8] Hazara Univ, Dept Chem, Mansehra 21120, Khyber Pukhtunk, Pakistan

[9] King Abdulaziz Univ, Dept Biochem, Fac Sci, Jeddah 21412, Saudi Arabia

来源：

BIOORGANIC CHEMISTRY | 2015年 / 63卷

关键词：

2-Indolcarbohydrazones; alpha-Glucosidase inhibition; Structure-activity relationship; Density Functional Theory (DFT); In silico studies; CRYSTAL-STRUCTURE; SCHIFF-BASES; ANTIOXIDANT ACTIVITY; MOLECULAR DOCKING; VITRO EVALUATION; DERIVATIVES; PHARMACOLOGY; MECHANISM; APOPTOSIS; ANALOGS;

D O I：

10.1016/j.bioorg.2015.09.001

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：

2-Indolcarbohydrazones 1-28 were synthesized and evaluated for their alpha-glucosidase inhibitory potential. A varying degree of inhibitory potential with IC50 values in the range of 2.3 +/- 0.11-226.4 +/- 6.8 mu M was observed while comparing these outcomes with the standard acarbose (IC50 = 906.0 +/- 6.3 mu M). The stereochemistry of ten (10) randomly selected compounds (1, 3, 6, 8, 12, 18, 19, 23, 25 and 28) was predicted by Density Functional Theory (DFT). The stability of E isomer was deduced by comparing the calculated and experimental vibration modes of nu(C=O), nu(N=C) and nu(CH) (CH in -N=CH-R). It was observed that except compound 18, all other compounds were deduced to have E configuration while molecular modeling studies revealed the key interactions between enzyme and synthesized compounds. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：24 / 35

页数：12

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