Schiff Bases of Indoline-2,3-dione: Potential Novel Inhibitors of Mycobacterium Tuberculosis (Mtb) DNA Gyrase

被引：43

作者：

Aboul-Fadl, Tarek ^{[1
]}

Abdel-Aziz, Hatem A. ^{[1
]}

Abdel-Hamid, Mohammed K. ^{[2
]}

Elsaman, Tilal ^{[1
]}

Thanassi, Jane ^{[3
]}

Pucci, Michael J. ^{[3
]}

机构：

[1] King Saud Univ, Coll Pharm, Dept Pharmaceut Chem, Riyadh 11451, Saudi Arabia

[2] Assiut Univ, Dept Pharmaceut Med Chem, Fac Pharm, Assiut 71526, Egypt

[3] Achill Pharmaceut, Antimicrobial Drug Discovery, New Haven, CT 06511 USA

来源：

MOLECULES | 2011年 / 16卷 / 09期

关键词：

Schiff bases; Indoline-2,3-dione; microwave irradiation; Mycobacterium tuberculosis (Mtb); Mtb DNA gyrase; MOE; ANTIBACTERIAL ACTIVITY; TOPOISOMERASE; DISCOVERY;

D O I：

10.3390/molecules16097864

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 the present study a series of Schiff bases of indoline-2,3-dione were synthesized and investigated for their Mtb gyrase inhibitory activity. Promising inhibitory activity was demonstrated with some of these derivatives, which exhibited IC50 values ranging from 50-157 mu M. The orientation and the ligand-receptor interactions of such molecules within the Mtb DNA gyrase A subunit active site were investigated applying a multi-step docking protocol using Molecular Operating Environment (MOE) and Autodock4 docking software. The results revealed the importance of the isatin moiety and the connecting side chain for strong interactions with the enzyme active site. Among the tested compounds the terminal aromatic ring benzofuran showed the best activity. Promising new leads for developing a novel class of Mtb gyrase inhibitors were obtained from Schiff bases of indoline-2,3-dione.

引用

页码：7864 / 7879

页数：16

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