Diketopiperazine Alkaloids Produced by the Endophytic Fungus Aspergillus fumigatus from the Stem of Erythrophloeum fordiiOliv.

Abstract

Four new diketopiperazine alkaloids, rel‐(8R)‐9‐hydroxy‐8‐methoxy‐18‐epi‐fumitremorgin C (1), rel‐(8S)‐19,20‐dihydro‐9,20‐dihydroxy‐8‐methoxy‐9,18‐di‐epi‐fumitremorgin C (2), rel‐(8S,19S)‐19,20‐dihydro‐9,19,20‐trihydroxy‐8‐methoxy‐9‐epi‐fumitremorgin C (3), and (3S,8S,9S,18S)‐8,9‐dihydroxyspirotryprostatin A (4), together with the eight known compounds 5–12, were isolated from the endophytic fungus Aspergillus fumigatus. The structures of the new compounds were determined by extensive spectroscopic methods including HR‐ESI‐MS, NMR, and CD experiments. Compound 12 showed weak inhibitory activity in vitro against the release of β‐glucuronidase in rat polymorphonuclear leukocytes induced by the platelet‐activating factor. None of the twelve compounds exhibited detectable cytotoxic activities toward five human tumor cell lines (HCT‐8, Bel‐7402, BGC‐823, A549, and A2780) in the MTT assay.

Penicillivinacine, antimigratory diketopiperazine alkaloid from the marine-derived fungus Penicillium vinaceum

“…Terretrione A (4) was previously reported from mangrove-associated fungus Aspergillus terreus (Shen et al, 2012). Compounds 5 and 6 were proved to be diketopiperazine derivatives, where 5 was identified as brevianamide F which was previously isolated from the fungus Aspergillus fumigates, while 6 was found the diastereomer of 5, cyclo-D-Trp-L-pro (Liu et al, 2012;Grundmann and Li, 2005). Finally, compound 7 was identified as the isocoumarin derivative citreoisocoumarin that was previously reported from the fungus Penicillium nalgiovense (Larsen and Breinholt, 1999).…”

Endophytic Fungi as a Source of Novel Metabolites

“…However, unlike those generally reported diketopiperazines, compound 295 possesses a spirocyclic moiety, typical in the spirotryprostatin class. Neither significant anti-inflammatory activity, nor detectable cytotoxicity (IC 50 > 10 μM) toward five human tumor cell lines were displayed by this compound during the bioassay [78]. A novel diketopiperazine derivative containing an isopentenyl moiety attached (299, Fig.…”

“…No anti-inflammatory activity, and no tumor cell cytotoxicity [200] Verruculogen TR2-derivative (296)…”

“…No anti-inflammatory activity, no tumor cell cytotoxicity [200] Rel-(8S,19S)-19,20-Dihydro-9,19,20-trihydroxy-8-methoxy-9-epi-fumitremorgin C (294)…”

“…No anti-inflammatory activity, and no tumor cell cytotoxicity [200] (3S,8S,9S,18S)-8,9-dihydroxyspirotryprostatin A (295)…”