title: Cytotoxic 14-Membered Macrolides from a Mangrove-Derived Endophytic Fungus, Pestalotiopsis microspora.
abstract: Seven new 14-membered macrolides, pestalotioprolides C (2), D-H (4-8), and 7-O-methylnigrosporolide (3), together with four known analogues, pestalotioprolide B (1), seiricuprolide (9), nigrosporolide (10), and 4,7-dihydroxy-13-tetradeca-2,5,8-trienolide (11), were isolated from the mangrove-derived endophytic fungus Pestalotiopsis microspora. Their structures were elucidated by analysis of NMR and MS data and by comparison with literature data. Single-crystal X-ray diffraction analysis was used to confirm the absolute configurations of 1, 2, and 10, while Mosher's method and the TDDFT-ECD approach were applied to determine the absolute configurations of 5 and 6. Compounds 3-6 showed significant cytotoxicity against the murine lymphoma cell line L5178Y with IC50 values of 0.7, 5.6, 3.4, and 3.9 μM, respectively, while compound 5 showed potent activity against the human ovarian cancer cell line A2780 with an IC50 value of 1.2 μM. Structure-activity relationships are discussed. Coculture of P. microspora with Streptomyces lividans caused a roughly 10-fold enhanced accumulation of compounds 5 and 6 compared to axenic fungal control.
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biology and Genetic Resources of Tropical Crops, Ministry of Agriculture, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences , Haikou 571101, China.
authors.forename: Haofu
authors.initials: H
authors.lastname: Dai
authors.forename: Gamall
authors.initials: G
authors.lastname: Makhloufi
authors.forename: Christian
authors.initials: C
authors.lastname: Heering
authors.forename: Christoph
authors.initials: C
authors.lastname: Janiak
authors.affiliation: Institute of Complex Systems: Strukturbiochemie, Forschungszentrum Juelich , Wilhelm-Johnen-Straße, 52428 Juelich, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hartmann
authors.affiliation: Department of Organic Chemistry, University of Debrecen , P.O. Box 400, H-4002 Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Mándi
authors.affiliation: Department of Organic Chemistry, University of Debrecen , P.O. Box 400, H-4002 Debrecen, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kurtán
authors.affiliation: Institute of Physiological Chemistry, Universitätsmedizin der Johannes Gutenberg-Universität Mainz , Duesbergweg 6, 55128 Mainz, Germany.
authors.forename: Werner E G
authors.initials: WE
authors.lastname: Müller
authors.forename: Matthias U
authors.initials: MU
authors.lastname: Kassack
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University , Beijing 100191, China.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Lin
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
mesh_terms: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002163:Cameroon; D018360:Crystallography, X-Ray; D007887:Fabaceae / Q000382:microbiology; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008968:Molecular Conformation; D015394:Molecular Structure; D011500:Protein Synthesis Inhibitors; D013329:Structure-Activity Relationship; D013098:Xylariales / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D018942:Macrolides; D011500:Protein Synthesis Inhibitors