Chlovalicin, a new cytocidal antibiotic produced by Sporothrix sp. FO-4649. I. Taxonomy, fermentation, isolation and biological activities.
Selective growth inhibition against IL-6 dependent cells was detected in fermentation extracts of a fungal strain FO-4649 which was characterized as Sporothrix species. An active metabolite (1) termed chlovalicin was isolated together with ovalicin and two other ovalicin derivatives (compounds 3 and 4). Chlovalicin, a ovalicin derivative with a chlorinated methylene moiety at the C-1 position of the cyclohexane ring, dose-dependently inhibited the growth of IL-6 dependent MH60 cells (IC50, 7.5 microM) in the presence of 0.2 U/ml IL-6 and, to a lesser extent, the growth of B16 melanoma cells (IC50, 38 microM). Among the other three compounds, only ovalicin showed inhibitory activity (IC50, 27 microM) against MH60 cells. These four compounds did not show any antimicrobial activity at a concentration of 1000 micrograms/ml.
Hayashi
M
M
Kitasato Institute, Kitasato University, Tokyo, Japan.
Kim
Y P
YP
Takamatsu
S
S
Preeprame
S
S
Komiya
T
T
Masuma
R
R
Tanaka
H
H
Komiyama
K
K
Omura
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000302:isolation & purification* / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002457:Cell Extracts; D002478:Cells, Cultured; D003512:Cyclohexanones / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D005285:Fermentation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008826:Microbial Sensitivity Tests; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology; D013175:Sporothrix / Q000145:classification / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D002457:Cell Extracts; D003512:Cyclohexanones; D004852:Epoxy Compounds; D015850:Interleukin-6; D012717:Sesquiterpenes; C101438:chlovalicin; C002781:ovalicin