A phthalide with in vitro growth inhibitory activity from an oidiodendron strain.
A screening campaign was implemented utilizing capillary electrophoresis as a primary assay to discover binders to the cancer target Akt1 from a crude natural extract library. Fungal extracts with binding activities were characterized for biochemical inhibition of Akt1 to phosphorylate the downstream substrate protein Bad. One of the crude extracts with bioactivity selected for isolation and structure elucidation from fermentation of the fungal culture Oidiodendron sp. F01895 yielded a new trihydroxy phthalide (1). The structure of 1 was determined by a combination of 1D and 2D NMR spectroscopic data along with high-resolution mass spectrometric data. Compound 1 displays inhibition of Akt1 biochemical activity in vitro and confers growth inhibition on some cancer-derived cell lines in culture.
Mullady
Erin L
EL
Cetek Corporation, 260 Cedar Hill Street, Marlborough, Massachusetts 01752, USA.
Millett
William P
WP
Yoo
Hye-Dong
HD
Weiskopf
Andrew S
AS
Chen
Jianxin
J
Ditullio
Dennis
D
Knight-Connoni
Victoria
V
Hughes
Dallas E
DE
Pierceall
William E
WE
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005658:Fungi / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D051057:Proto-Oncogene Proteins c-akt; D014407:Tumor Cells, Cultured
C497287:4,5,6-trihydroxy-3-methylphthalide; D000970:Antineoplastic Agents; D001572:Benzofurans; D011518:Proto-Oncogene Proteins; C082022:phthalide; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt