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.
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 f uckeliana MCCC 3A00494, a fungus isolated from the western Pacific Ocean (−5572 m). The structures of 1−71 were determined through extensive spectroscopic analysis, Xray 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 (IC 50 = 2.5 μM) and HL-60 (IC 50 = 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.
A new pimarane diterpenoid, named botryopimarene A (1), was discovered from the fungus Botryotinia fuckeliana MCCC 3 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 Mo 2 (OAc) 4 -induced ECD spectrum. Compound 1, featuring a Δ 9(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 (IC 50 > 20 μM).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.