title: Filamenting temperature-sensitive mutant Z inhibitors from Glycyrrhiza glabra and their inhibitory mode of action.
abstract: FtsZ is an essential protein for bacterial cell division, and an attractive and underexploited novel antibacterial target protein. Screening of Indonesian plants revealed the inhibitory activity of the methanol extract of Glycyrrhiza glabra on the Bacillus subtilis FtsZ (BsFtsZ) GTPase, and further bioassay-guided fractionation of the active methanol extract led to the isolation of seven known polyketides (1-7). Among them, gancaonin I (1), glycyrin (3), and isolicoflavanol (5) exhibited anti-BsFtsZ GTPase activities, at levels comparable to that of the synthetic FtsZ inhibitor, Zantrin Z3. Enzymatic assays using a BsFtsZ Val307R mutant protein and in silico simulations suggested that 1, 3, and 5 bind to the cleft on BsFtsZ, as in the case of the previously reported uncompetitive FtsZ inhibitor, PC190723, and thereby display their significant anti-BsFtsZ inhibitory activities. Furthermore, 1 also showed significant inhibitory activity against B. subtilis, with a MIC value of 5μM. The present study provides new insights into the naturally occurring B. subtilis growth inhibitors.
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama 930-0194, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Faculty of Pharmacy, Hasanuddin University, Jl. Perintis Kemerdekaan Km 10, Makassar 90245, Indonesia.
authors.forename: Subehan
authors.initials: S
authors.lastname: Lallo
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama 930-0194, Japan; Research Unit for Natural Products Technology, Indonesian Institute of Sciences, Jl. Jogja-Wonosari Km. 32, Playen, Gunungkidul, Yogyakarta 55861, Indonesia.
authors.forename: Khoirun
authors.initials: K
authors.lastname: Nisa
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama 930-0194, Japan. Electronic address: hmorita@inm.u-toyama.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D006035:Glycyrrhiza / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010936:Plant Extracts / Q000494:pharmacology*; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents; D010936:Plant Extracts
keywords: Antibacterials; Docking simulation; FtsZ inhibitor; Glycyrrhiza glabra