ABSTRACT
Eight unprecedent diterpenoids, botryotins A-H (1-8), were obtained from Botryotinia fuckeliana. They represent three novel carbon skeletons with 6/6/5/5 (1), 6/6/5/6 (2-6), and 6/6/6/5 (7 and 8) tetracyclic scaffolds. Their structures were determined by detailed spectroscopic analysis and chemical derivatization as well as quantum chemical calculation of the ECD and OR data. Botryotin A (1) exhibited a moderate antiallergic effect (IC50 = 0.2 mM). A plausible biosynthetic pathway for 1-8 was proposed.
Subject(s)
Anti-Allergic Agents/pharmacology , Botrytis/chemistry , Diterpenes/pharmacology , Hypersensitivity/drug therapy , Animals , Anti-Allergic Agents/chemistry , Anti-Allergic Agents/isolation & purification , Cell Line, Tumor , Diterpenes/chemistry , Diterpenes/isolation & purification , Dose-Response Relationship, Drug , Humans , Mice , RAW 264.7 Cells , RatsABSTRACT
A new pimarane diterpenoid, named botryopimarene A (1), was discovered from the fungus Botryotinia fuckeliana MCCC 3â A00494 isolated from the deep-sea water, together with ten known compounds. The planar structure of 1 was established based on the extensive spectroscopic analyses. The absolute configurations of tricyclic system in 1 were resolved by the theoretical ECD calculation, while the 15,16-diol moiety in the side chain was resolved by the Mo2 (OAc)4 -induced ECD spectrum. Compound 1, featuring a Δ9(11) double bond, was rarely discovered in pimarane family. Compounds 1-11 were tested for their cytotoxic activities using six human cancer cell lines by the MTT method. However, none of the compounds exhibited detectable cytotoxicities (IC50 >20â µm).
Subject(s)
Abietanes/chemistry , Ascomycota/chemistry , Diterpenes/chemistry , Seawater/microbiology , Abietanes/isolation & purification , Abietanes/pharmacology , Ascomycota/isolation & purification , Ascomycota/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Circular Dichroism , Diterpenes/isolation & purification , Diterpenes/pharmacology , Humans , Molecular ConformationABSTRACT
Aphidicolin, a potent DNA polymerase α inhibitor, has been explored in clinical trials for the treatment of cancer. So far, about 300 modified aphidicolins have been discovered. However, none have shown a stronger effect. Herein, we report 71 new (aphidicolins A1-A71, 1-71) and eight known (72-79) aphidicolin congeners from Botryotinia fuckeliana MCCC 3A00494, a fungus isolated from the western Pacific Ocean (-5572 m). The structures of 1-71 were determined through extensive spectroscopic analysis, X-ray crystallography, chemical derivatization, modified Mosher's method, and the ECD exciton chirality method. Compounds 54-57 and 58-64 are novel 6/6/5/6/5 pentacyclic aphidicolins featuring tetrahydrofuran and dihydrofuran rings, respectively, while compounds 65-71 are rare noraphidicolins. Aphidicolin A8 (8) significantly induced apoptosis in T24 (IC50 = 2.5 µM) and HL-60 (IC50 = 6.1 µM) cancer cells by causing DNA damage. By docking its structure to the human DNA polymerase α binding pocket, 8 was found to form tight intermolecular contacts, elaborating aphidicolin A8 as a potently cytotoxic lead compound.
