title: 3-Anhydro-6-hydroxy-ophiobolin A, a new sesterterpene inhibiting the growth of methicillin-resistant Staphylococcus aureus and inducing the cell death by apoptosis on K562, from the phytopathogenic fungus Bipolaris oryzae.
abstract: A new ophiobolin derivative, 3-anhydro-6-hydroxy-ophiobolin A (1), as well as two known ophiobolin derivatives 3-anhydro-ophiobolin A (2) and 3-anhydro-6-epi-ophiobolin A (3) were isolated from the PDB culture of a phytopathogenic fungus Bipolaris oryzae. The structure of 1 was elucidated through 2D NMR and other spectroscopic techniques. Compound 1 exhibited strong antimicrobial activity against Bacille Calmette-Guerin, Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus with MIC value of 12.5 μg/mL, and potent antiproliferative activity against cell lines HepG2 and K562 with IC50 of 6.49 μM and 4.06 μM, respectively. Further studies on the cytotoxicity of compound 1 against K562 cells demonstrated that it induced apoptosis, observed by flow cytometric method. Preliminary structure-activity relationships of these ophiobolins and the mechanism of apoptosis induced by 1 were analyzed.
authors.affiliation: State Key Lab of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No. 8 Beiertiao, Zhongguancun, Haidian District, Beijing 100190, PR China.
authors.forename: Quan-Xin
authors.initials: QX
authors.lastname: Wang
authors.forename: Jian-Ling
authors.initials: JL
authors.lastname: Yang
authors.forename: Qiu-Yue
authors.initials: QY
authors.lastname: Qi
authors.forename: Li
authors.initials: L
authors.lastname: Bao
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Yang
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Liu
authors.forename: Pei
authors.initials: P
authors.lastname: Huang
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Zhang
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D020014:K562 Cells; D055624:Methicillin-Resistant Staphylococcus aureus / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D012275:Oryza / Q000737:chemistry*; D054830:Sesterterpenes / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D054830:Sesterterpenes; C002884:ophiobolins