title: Schiff bases of indoline-2,3-dione: potential novel inhibitors of Mycobacterium tuberculosis (Mtb) DNA gyrase.
abstract: 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 IC(50) values ranging from 50-157 mM. 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.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. fadl@ksu.edu.sa
authors.forename: Tarek
authors.initials: T
authors.lastname: Aboul-Fadl
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Abdel-Aziz
authors.forename: Mohammed K
authors.initials: MK
authors.lastname: Abdel-Hamid
authors.forename: Tilal
authors.initials: T
authors.lastname: Elsaman
authors.forename: Jane
authors.initials: J
authors.lastname: Thanassi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pucci
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D027081:DNA Gyrase / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D012545:Schiff Bases / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D012545:Schiff Bases; C572590:indoline-2,3-dione; D027081:DNA Gyrase