Sorbicillactone A: a structurally unprecedented bioactive novel-type alkaloid from a sponge-derived fungus.
This chapter deals with the discovery of sorbicillactone A, as an illustrative example of the fruitful cooperation within BIOTECmarin--its isolation and chemical characterization, and its biological activities. Sorbicillactone A was isolated from a strain of Penicillium chrysogenum cultured from a sample of the Mediterranean sponge Ircinia fasciculata; it possesses a unique bicyclic lactone structure, seemingly derived from sorbicillin. Among the numerous known sorbicillin-derived structures, it is the first found to contain nitrogen and thus the first representative of a novel type of 'sorbicillin alkaloids', apparently originating from a likewise remarkable biosynthesis. Furthermore, the compound exhibits promising activities in several mammalian and viral test systems, in particular a highly selective cytostatic activity against murine leukemic lymphoblasts (L5178y) and the ability to protect human T cells against the cytopathic effects of HIV-1. These properties qualify sorbicillactone A or one of its derivatives for animal and (hopefully) also future therapeutic human trials.
Bringmann
G
G
Institute of Organic Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Lang
G
G
Mühlbacher
J
J
Schaumann
K
K
Steffens
S
S
Rytik
P G
PG
Hentschel
U
U
Morschhäuser
J
J
Müller
W E G
WE
D000470:Alkaloids / Q000737:chemistry*; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D017209:Apoptosis; D001572:Benzofurans / Q000737:chemistry* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D005658:Fungi / Q000378:metabolism*; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism; D007940:Leukemia L5178 / Q000188:drug therapy / Q000821:virology; D013058:Mass Spectrometry; D051379:Mice; D008956:Models, Chemical; D010407:Penicillium / Q000378:metabolism; D011161:Porifera / Q000382:microbiology; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D013997:Time Factors
D000470:Alkaloids; D019380:Anti-HIV Agents; D000935:Antifungal Agents; D001572:Benzofurans; D007783:Lactones; C500693:sorbicillactone A