Anti-proliferative ambuic acid derivatives from Hawaiian endophytic fungus Pestalotiopsis sp. FT172

• Published in: Phytochemistry (Oxford) 2017-08, Vol.140, p.77-82
• Main Authors: Li, Chun-Shun, Yang, Bao-Jun, Turkson, James, Cao, Shugeng
• Format: Article
• Language: English
• Subjects: Ambuic acid; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antiproliferative; Cell Line, Tumor; Cyclohexanones - chemistry; Cyclohexanones - isolation & purification; Endophytes - chemistry; Endophytic fungi; Hawaii; Humans; Molecular Structure; Myrsinaceae; Myrsinaceae - microbiology; Myrsine sandwicensis; Pestalotiopsis; Xylariales - chemistry
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2017.04.017

Five previously undescribed ambuic acid derivatives, pestallic acids A–E and three known analogs were isolated from the cultured broth of Pestalotiopsis sp. FT172. The structures of the pestallic acids A-E were determined through the analysis of HRMS and NMR spectroscopic data. The absolute configurations (ACs) of pestallic acids B–E were assigned by comparison of the experimental electric circular dichroism (ECD) spectra or the optical rotations with those in the literature. All compounds were tested against A2780 and cisplatin resistant A2780 (A2780CisR) cell lines. Pestallic acid E and (+)-ambuic acid showed potent activities with IC50 values from 3.3 to 17.0 μM. Bioassay-guided fractionation of an extract from a Hawaiian endophytic fungus Pestalotiopsis sp. FT172 led to the isolation of eight compounds, including five previously undescribed ambuic acid derivatives pestallic acids A–E. Their chemical structures were determined by HRMS and NMR spectroscopy. All isolates were evaluated for their anti-proliferative activity against A2780 and cisplatin-resistant A2780 (A2780CisR) cancer cell lines. Pestallic acid E showed potent anti-proliferative activity against A2780 and A2780CisR cell lines with IC50 values of 3.3 and 5.1 μM, respectively, and (+)-ambuic acid demonstrated inhibitory activity against the above two cancer cell lines with IC50 values of 10.1 and 17.0 μM, respectively. [Display omitted] •Pestalotiopsis sp. FT172 is the first fungus isolated from Myrsine sandwicensis.•Pestallic acids A–E from Pestalotiopsis sp. FT172 have not been reported before.•The configurations of pestallic acids B–E were determined by using CD and polarimetry.•Pestallic acid E had an IC50 value of 3.3 μM against A2780 cancer cell line.