Chlovalicin B, a Chlorinated Sesquiterpene Isolated from the Marine Mushroom Digitatispora marina

Abstract

As part of our search for bioactive metabolites from understudied marine microorganisms, the new chlorinated metabolite chlovalicin B (1) was isolated from liquid cultures of the marine basidiomycete Digitatispora marina, which was collected and isolated from driftwood found at Vannøya, Norway. The structure of the novel compound was elucidated by spectroscopic methods including 1D and 2D NMR and analysis of HRMS data, revealing that 1 shares its molecular scaffold with a previously isolated compound, chlovalicin. This represents the first compound isolated from the Digitatispora genus, and the first reported fumagillin/ovalicin-like compound isolated from Basidiomycota. Compound 1 was evaluated for antibacterial activities against a panel of five bacteria, its ability to inhibit bacterial biofilm formation, for antifungal activity against Candida albicans, and for cytotoxic activities against malignant and non-malignant human cell lines. Compound 1 displayed weak cytotoxic activity against the human melanoma cell line A2058 (~50% survival at 50 µM). No activity was detected against biofilm formation or C. albicans at 50 µM, or against bacterial growth at 100 µM nor against the production of cytokines by the human acute monocytic leukemia cell line THP-1 at 50 µM.

Marine natural products

“…185 Dichocetide D 438 is a symmetrical dichlorinated metabolite obtained from Dichotomomyces cejpii, 186 and chlorinated sesquiterpene chlovalicin B 439 was isolated from a Digitatispora strain. 187 Epicoccum nigrum yielded cyclic tripeptide 440, 188 while several salicaldehyde derivatives 441-444, 189 445-451, 190 452-457 191 and a diketopiperazine 458, 192 were obtained from Eurotium strains. Epigenetic manipulation of a Eutypella species activated a BGC, resulting in isolation of 17 sesquiterpenes, eutypeterpenes A-Q 459-475.…”

A Survey of Recently Discovered Naturally Occurring Organohalogen Compounds

“…It shows some cytotoxicity against IL-6 dependent MH60 cells (IC 50 7.5 μM). 82 The Antarctica sponge-derived fungus Alternaria sp. HDN19-690 yielded the novel altertoxin VIII (188), which is active against E. coli (MIC 6.25 μM; ciprofloxacin, 0.025 μM).…”

“…The single stereocenter is assigned based on that of the known chlovalicin having a methoxyl group in place of the hydroxyl group next to the carbonyl. It shows some cytotoxicity against IL-6 dependent MH60 cells (IC 50 7.5 μM) . The Antarctica sponge-derived fungus Alternaria sp.…”

Marine Compounds for Melanoma Treatment and Prevention

“…Very recently, another compound Chlovalicin B was isolated from the marine fungus Digiratispora marina , taken from driftwood harvested in Vannoya in Norway in 2010 [ 24 ]. This compound exhibited mild cytotoxic activity against human A2058 melanoma cells with approximately 50% survival at 50 µM.…”