6533b82efe1ef96bd1292841

RESEARCH PRODUCT

Cytotoxic 14-Membered Macrolides from a Mangrove-Derived Endophytic Fungus, Pestalotiopsis microspora.

Werner E. G. M�llerGamall MakhloufiWenhan LinMatthias U. KassackRudolf HartmannZhen LiuAttila MándiShuai LiuChristoph JaniakTibor KurtánPeter ProkschChristian HeeringHao-fu Dai

subject

StereochemistryMolecular ConformationPharmaceutical ScienceAntineoplastic Agents010402 general chemistryCrystallography X-Ray01 natural sciencesAnalytical ChemistryStructure-Activity RelationshipTermészettudományokDrug DiscoveryMicrosporaCytotoxic T cellStructure–activity relationshipHumansCameroonKémiai tudományokCytotoxicityIC50PharmacologyProtein Synthesis InhibitorsbiologyMolecular StructureXylariales010405 organic chemistryOrganic ChemistryPestalotiopsis microsporaFabaceaeEndophytic fungusbiology.organism_classification0104 chemical sciencesAnti-Bacterial AgentsComplementary and alternative medicineCell cultureMolecular MedicineMacrolides

description

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.

yearjournalcountryeditionlanguage
2016-08-25Journal of natural products
10.1021/acs.jnatprod.6b00473https://pubmed.ncbi.nlm.nih.gov/27556865