A New Cytotoxic Trichothecene Macrolide from the EndophyteMyrothecium roridum

Abstract

A new cytotoxic roridin-type trichothecene macrolide named roritoxin E(1) was characterized from the solid culture of Myrothecium roridum IFB-E091 (residing originally inside Artemisia annua root), together with the known compounds lumichrome (2), (22 E,24 S)-cerevisterol (3), and (22 E,24 R)-6 beta-methoxy-ergosta-7,22-diene-3 beta,5 alpha-diol (4). The structure of the new macrolide (1) was elucidated by a combination of spectroscopic (UV, IR, MS, and 1D and 2D NMR) analyses. Compound 1 was demonstrated to be inhibitory in vitro against the gastric carcinoma SGC-7901 and hepatocarcinoma SMMC-7721 cell lines, with IC (50) values of 0.26 and 10.54 microg/mL, respectively. 5-Fluorouracil co-assayed as a positive control had an IC (50) value of 6.66 microg/mL against SGC-7901 cells, and it demonstrated only a 9.98 % growth inhibition against SMMC-7721 cells at 10 microg/mL.

Recent Advances on Macrocyclic Trichothecenes, Their Bioactivities and Biosynthetic Pathway

“…[ 7 , 10 , 28 ]. Macrocyclic trichothecenes are produced by the genera Myrothecium [ 29 , 30 , 31 ], Podostroma [ 32 ], Stachybotrys [ 33 ], Calcarisporium [ 34 ], Cercophora [ 35 ], Cylindrocarpon [ 36 ], Dendrodochium [ 37 ], Phomopsis [ 38 ], and Verticinimonosporium [ 39 ]. It is worth noting that Baccharis , belonging to the Asteraceae family, is the only plant genus that can produce trichothecenes [ 40 ].…”

“…The second ring is closed by the connecting between C-6′ and C-12′ of the side chain. A third ring exists in some compounds, which is formed via an ester linkage between C-12′ and C-14′ ( 9 , 10 , 15 ) [ 30 , 44 ]. Roritoxin E ( 10 ) [ 30 ], 6′,12′-epoxymyrotoxin A ( 11 ) [ 45 ], and 2′,3′-epoxymyrothecine A ( 18 ) [ 46 ] have the epoxide ring at C-2′, C-3′; furthermore, 6′,12′-epoxymyrotoxin A ( 11 ) has an additional epoxide ring at C-6′, C-12′.…”

“…A third ring exists in some compounds, which is formed via an ester linkage between C-12′ and C-14′ ( 9 , 10 , 15 ) [ 30 , 44 ]. Roritoxin E ( 10 ) [ 30 ], 6′,12′-epoxymyrotoxin A ( 11 ) [ 45 ], and 2′,3′-epoxymyrothecine A ( 18 ) [ 46 ] have the epoxide ring at C-2′, C-3′; furthermore, 6′,12′-epoxymyrotoxin A ( 11 ) has an additional epoxide ring at C-6′, C-12′. Due to the absence of the epoxide at C-12, C-13, compounds 12 – 20 belong to 10,13-cyclotrichothecane derivatives [ 44 , 47 ].…”

Natural sesquiterpenoids

“…106 7 Trichothecane, herbertane, laurane and cuparane A new cytotoxic trichothecene macrolide, roritoxin E 128, has been obtained from solid cultures of Myrothecium roridum, which had been isolated from the roots of Artemisia annua. 107 The dereplication of macrocyclic trichothecenes from extracts of filamentous fungi, using UV and NMR profiles, has been studied. 108 Three novel herbertane sesquiterpenes 129-131 have been found in an extract of Herbertus dicramus, 109 whilst known biologically-active sesquiterpenes of this type have been isolated from the Tahitian liverwort Mastigophora diclados.…”

Trichothecenes from a Soil-Derived Trichoderma brevicompactum

“…Fungi have gained predominance as a source of interesting bioactive natural products. , Trichothecenes, a family of sesquiterpenes, are produced by various fungal genera including Fusarium , Myrothecium , and Trichoderma . Trichodermin, a trichothecene derivative, is antifungal, nematicidal, and antiviral .…”