Microbial transformation of spirolaxine, a bioactive undecaketide fungal metabolite from the basidiomycete Sporotrichum laxum.
Incubation of (+)-spirolaxine (= (3R)-5-hydroxy-7-methoxy-3-{5-[(2R,5R,7R)-2-methyl-1,6-dioxaspiro[4.5]dec-7-yl]pentyl}-2-benzofuran-1(3H)-one; 1a) with Bacillus megaterium afforded two new mono- and one new dihydroxylated metabolite(s), all OH groups being introduced on the non-activated six-membered ring. In contrast, exposure of 1a to Cunninghamella echinulata gave rise to hydroxylation on the five-membered ring of the parent structure. The structures and absolute configurations of the new products 1b-e were deduced on the basis of MS and NMR data. The metabolite 1b was investigated, in comparison to 1a, for its cytotoxicity (sulforhodamin-B test) and for its antiproliferative activity towards bovine microvascular endothelial cells (BMEC).
Nasini
Gianluca
G
CNR-ICRM, Department of Chemistry, Materials and Chemical Engineering, Politecnico di Milano, via Mancinelli, 7, I-20123, Milano. gianluca.nasini@polimi.it
Bava
Adriana
A
Fronza
Giovanni
G
Giannini
Giuseppe
G
D000818:Animals; D001572:Benzofurans / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002470:Cell Survival; D002478:Cells, Cultured; D042783:Endothelial Cells; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013141:Spiro Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013175:Sporothrix / Q000737:chemistry* / Q000378:metabolism*; D014169:Transformation, Bacterial / Q000187:drug effects*
C526075:5-hydroxy-7-methoxy-3-(5-(2-methyl-1,6-dioxaspiro(4,5)dec-7-yl)pentyl)-2-benzofuran-1(3H)-one; D001572:Benzofurans; D013141:Spiro Compounds