Chaetoglobosins from Chaetomium globosum, an Endophytic Fungus in Ginkgo biloba, and Their Phytotoxic and Cytotoxic Activities

Abstract

In preceding studies, cultivation of Chaetomium globosum, an endophytic fungus in Ginkgo biloba, produced five cytochalasan mycotoxins, chaetoglobosins A, G, V, Vb, and C (1-5), in three media. In the present work, five known chaetoglobosins, C, E, F, Fex, and 20-dihydrochaetoglobosin A (5-9), together with the four known compounds (11-14), were isolated from the MeOH extracts of the solid culture of the same endophyte. The structures of these metabolites were elucidated on the basis of spectroscopic analysis. Treatment of chaetoglobosin F (7) with (diethylamino)sulfur trifluoride (DAST) in dichloromethane afforded an unexpected fluorinated chaetoglobosin, named chaetoglobosin Fa (10), containing an oxolane ring between C-20 and C-23. The phytotoxic effects of compounds 1, 3-8, and 10 were assayed on radish seedlings; some of these compounds (1, 3, and 6-8) significantly inhibited the growth of radish (Raphanus sativus) seedlings with inhibitory rates of >60% at a concentration of 50 ppm, which was comparable or superior to the positive control, glyphosate. In addition, the cytotoxic activities against HCT116 human colon cancer cells were also tested, and compounds 1 and 8-10 showed remarkable cytotoxicity with IC50 values ranging from 3.15 to 8.44 μM, in comparison to the positive drug etoposide (IC50 = 2.13 μM). The epoxide ring between C-6 and C-7 or the double bond at C-6(12) led to a drastically increased cytotoxicity, and chaetoglobosin Fa (10) displayed a markedly increased cytotoxicity but decreased phytotoxicity.

Characterization of Cytochalasins from the Endophytic Xylaria sp. and Their Biological Functions

“…XXXX, XXX, XXX−XXX s), attributable to the tetrasubstituted endocyclic double bond in 1, were replaced by the two exocyclic double-bond carbon signals at δ C 151.9 (C-6, s) and 112.7 (C-12, t) in 2. This portion of the spectrum was also similar to that observed in the 13 C spectrum of 10-phenyl [12]cytochalasin Z 16 . 35 Furthermore, in the 1 H NMR spectrum of 2, the C-11 methyl proton signal (δ H 1.06, d, J = 6.6 Hz), appearing as a doublet instead of the singlet (δ H 1.52, s) as in 1, was also consistent with a methylsubstituted six-membered ring as seen in cytochalasin Z 16 .…”

“…35 This is not surprising because of the structural analogy between the two compounds; still, an independent proof of the absolute configuration of 1 was obtained by quantum mechanical calculations of its CD spectrum. It was concluded that 1 has the same configuration of cytochalasin Z 17 , and its structure is determined as (+)-(3S,4S,7S,8S,9S,13E,16S,18E)-7-hydroxy-5,6,16,18-tetramethyl-10-(4′-hydroxyphenyl)-22-oxa- [12]-cytochalasa-6,13,18-trien-1,17,21-trione.…”

Biological Evaluation of Endophytic Fungus Chaetomium sp. NF15 of Justicia adhatoda L.: A Potential Candidate for Drug Discovery

“…Several types of bioactive compounds have been reported from this unique fungal specie. Chaetomium species are able to produce antimicrobial, cytotoxic, anticancer, antimalarial, and antioxidant compounds with chemical diversity (11, 26). Chaetomium species have been used to produce of a plethora of pharmacologically active metabolites, including chaetoglobosins, cytoglobins, anthraquinones, steroids, azaphilones, alkaloids, and depsidones (11, 26, 27).…”

Histologic observation, identification, and secondary metabolites analysis of endophytic fungi isolated from a medicinal plant, hedychium acuminatum Roscoe

“…Endophytic fungi could produce antibiotic, antiviral, anticancer, and insecticide compounds [8,9]. The endophytic fungi species in Ginkgo biloba could produce active compounds that have characters antimicrobe, antioxidant, cytotoxic, etc [10][11][12][13][14]. The medicinal plants used frequently belongs to Zingiberaceae.…”