Synthesis of bis-indolylmethanes as new potential inhibitors of β-glucuronidase and their molecular docking studies

被引：67

作者：

Taha, Muhammad ^{[1
]}

Ullah, Hayat ^{[2
]}

Al Muqarrabun, Laode Muhammad Ramadhan ^{[3
,4
]}

Khan, Muhammad Naseem ^{[5
]}

Rahim, Fazal ^{[2
,3
]}

Ahmat, Norizan ^{[4
]}

Ali, Muhammad ^{[5
]}

Perveen, Shahnaz ^{[6
]}

机构：

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

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

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

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

[5] COMSATS Inst Informat Technol, Dept Chem, Abbottabad 22060, Pakistan

[6] Shahrah E Dr Salimuzzaman Siddiqui, PCSIR Labs Complex, Karachi 75280, Pakistan

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 143卷

关键词：

Synthesis; Bis-indolylmethanes; beta-Glucuronidase activity; Molecular docking; SAR; URINARY-TRACT-INFECTION; ALPHA-GLUCOSIDASE SYNTHESIS; IN-VITRO EVALUATION; VIBRINDOLE-A; BIOLOGICAL EVALUATION; SCHIFF-BASES; DISEASE; ANALOGS; CANCER; BIS(INDOLYL)METHANES;

D O I：

10.1016/j.ejmech.2017.10.071

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Thirty-two (32) bis-indolylmethane-hydrazone hybrids 1-32 were synthesized and characterized by (HNMR)-H-1, (CNNMR)-C-13 and HREI-MS. All compounds were evaluated in vitro for beta-glucuronidase inhibitory potential. All analogs showed varying degree of beta-glucuronidase inhibitory potential ranging from 0.10 +/- 0.01 to 48.50 +/- 1.10 mu M when compared with the standard drug D-saccharic acid-1,4-lactone (IC50 value 48.30 +/- 1.20 mu M). Derivatives 1-32 showed the highest P-glucuronidase inhibitory potentials which is many folds better than the standard drug n-saccharic acid-1,4-lactone. Further molecular docking study validated the experimental results. It was proposed that bis-indolylmethane may interact with some amino acid residues located within the active site of beta-glucuronidase enzyme. This study has culminated in the identification of a new class of potent beta-glucuronidase inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.

引用

页码：1757 / 1767

页数：11

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