Planta Med 2020; 86(13/14): 976-982
DOI: 10.1055/a-1091-8831
Biological and Pharmacological Activity
Original Papers

Trichothecenes from an Endophytic Fungus Alternaria sp. sb23

Ying Gao
School of Pharmacy, Tongji Medical College of Huazhong University of Science and Technology, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Wuhan, Peopleʼs Republic of China
,
Jia Zhou
School of Pharmacy, Tongji Medical College of Huazhong University of Science and Technology, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Wuhan, Peopleʼs Republic of China
,
Hanli Ruan
School of Pharmacy, Tongji Medical College of Huazhong University of Science and Technology, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Wuhan, Peopleʼs Republic of China
› Author Affiliations
Supported by: National Natural Science Foundation of China 31770380, 21572073, and 31270394

Abstract

Three new (alterchothecenes A – C, 1 –3) and 3 known (4 –6) trichothecenes, along with 9 known compounds (7 –15), were isolated from the culture of Alternaria sp. sb23, an endophytic fungus separated from the root of Schisandra sphenanthera Rehd. et Wils. Their structures were elucidated by spectroscopic analyses, and the absolute configurations of 13 were determined through comparison of the experimental electronic circular dichroism (ECD) spectra and optical rotations with similar analogues. In vitro cytotoxicity tests of compounds 16 against human HT-29 colon carcinoma and human MCF-7 breast cancer cell lines indicated that 46 exhibited significant cytotoxic effects, with IC50 values ranging from 0.89 to 9.38 µM. And the potential of compounds 16 as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) sensitizers in HT-29 cells was evaluated. The results revealed that combination treatment of TRAIL with compounds 16 synergistically decreased cell viability compared with the sole treatment with those compounds.

Supporting Information



Publication History

Received: 07 October 2019

Accepted after revision: 04 January 2020

Article published online:
04 February 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Stuttgart · New York

 
  • References

  • 1 Fruhmann P, Mikula H, Wiesenberger G, Varga E, Lumpi D, Stoger B, Haubl G, Lemmens M, Berthiller F, Krska R, Adam G, Hametner C, Frohlich J. Isolation and structure elucidation of pentahydroxyscirpene, a trichothecene Fusarium mycotoxin. J Nat Prod 2014; 77: 188-192
  • 2 Brase S, Encinas A, Keck J, Nising CF. Chemistry and biology of mycotoxins and related fungal metabolites. Chem Rev 2009; 109: 3903-3990
  • 3 Josephs RD, Derbyshire M, Stroka J, Emons H, Anklam E. Trichothecenes: reference materials and method validation. Toxicol Lett 2004; 153: 123-132
  • 4 Krska R, Baumgartner S, Josephs R. The state-of-the-art in the analysis of type-A and -B trichothecene mycotoxins in cereals. Fresenius J Anal Chem 2001; 371: 285-299
  • 5 Wu Q, Dohnal V, Huang L, Kuca K, Wang X, Chen G, Yuan Z. Metabolic pathways of ochratoxin A. Curr Drug Metab 2011; 12: 1-10
  • 6 Amagata T, Rath C, Rigot JF, Tarlov N, Tenney K, Valeriote FA, Crews P. Structures and cytotoxic properties of trichoverroids and their macrolide analogues produced by saltwater culture of Myrothecium verrucaria. J Med Chem 2003; 46: 4342-4350
  • 7 de Carvalho MP, Weich H, Abraham WR. Macrocyclic trichothecenes as antifungal and anticancer compounds. Curr Med Chem 2016; 23: 23-35
  • 8 Waterman C, Calcul L, Mutka T, Kyle DE, Pearce CJ, Baker BJ. A potent antimalarial trichothecene from Hyphomycete species. Tetrahedron Lett 2014; 55: 3989-3991
  • 9 Isaka M, Punya J, Lertwerawat Y, Tanticharoen M, Thebtaranonth Y. Antimalarial activity of macrocyclic trichothecenes isolated from the fungus Myrothecium verrucaria. J Nat Prod 1999; 62: 329-331
  • 10 Lakornwong W, Kanokmedhakul K, Soytong K, Unartngam A, Tontapha S, Amornkitbamrung V, Kanokmedhakul S. Types A and D trichothecene mycotoxins from the fungus Myrothecium roridum. Planta Med 2019; 85: 774-780
  • 11 Garcia CC, Rosso ML, Bertoni MD, Maier MS, Damonte EB. Evaluation of the antiviral activity against junin virus of macrocyclic trichothecenes produced by the hypocrealean epibiont of Baccharis coridifolia. Planta Med 2002; 68: 209-212
  • 12 Tani N, Dohi Y, Onji Y, Yonemasu K. Antiviral activity of trichothecene mycotoxins (deoxynivalenol, fusarenon-X, and nivalenol) against herpes simplex virus types 1 and 2. Microbiol Immunol 1995; 39: 635-637
  • 13 Matsumoto M, Nishiyama M, Maeda H, Tonouchi A, Konno K, Hashimoto M. Structure-activity relationships of trichothecenes against COLO201 cells and Cochliobolus miyabeanus: The role of 12-epoxide and macrocyclic moieties. Bioorg Med Chem Lett 2019; 29: 982-985
  • 14 McCormick SP, Stanley AM, Stover NA, Alexander NJ. Trichothecenes: from simple to complex mycotoxins. Toxins (Basel) 2011; 3: 802-814
  • 15 Karmakar UK, Ishikawa N, Arai MA, Ahmed F, Koyano T, Kowithayakorn T, Ishibashi M. Boesenberols, pimarane diterpenes with TRAIL-resistance-overcoming activity from Boesenbergia pandurata. J Nat Prod 2016; 79: 2075-2082
  • 16 Zhang LD, Fang BL. Mechanisms of resistance to TRAIL-induced apoptosis in cancer. Cancer Gene Ther 2005; 12: 228-237
  • 17 Park D, Ha IJ, Park SY, Choi M, Lim SL, Kim SH, Lee JH, Ahn KS, Yun M, Lee SG. Morusin induces TRAIL sensitization by regulating EGFR and DR5 in human glioblastoma cells. J Nat Prod 2016; 79: 317-323
  • 18 Sung B, Park B, Yadav VR, Aggarwal BB. Celastrol, a triterpene, enhances TRAIL-induced apoptosis through the down-regulation of cell survival proteins and up-regulation of death receptors. J Biol Chem 2010; 285: 11498-11507
  • 19 Prasad S, Yadav VR, Kannappan R, Aggarwal BB. Ursolic acid, a pentacyclin triterpene, potentiates TRAIL-induced apoptosis through p53-independent up-regulation of death receptors: evidence for the role of reactive oxygen species and JNK. J Biol Chem 2011; 286: 5546-5557
  • 20 Loukaci A, Kayser O, Bindseil KU, Siems K, Frevert J, Abreu PM. New trichothecenes isolated from Holarrhena floribunda. J Nat Prod 2000; 63: 52-56
  • 21 Zheng CJ, Sun PX, Jin GL, Qin LP. Sesquiterpenoids from Trichoderma atroviride, an endophytic fungus in Cephalotaxus fortunei. Fitoterapia 2011; 82: 1035-1038
  • 22 Berg A, Wangun HVK, Nkengfack AE, Schlegel B. Lignoren, a new sesquiterpenoid metabolite from Trichoderma lignorum HKI 0257. J Basic Microbiol 2004; 44: 317-319
  • 23 Dockerill B, Hanson JR, Siverns MJP. The 13C NMR spectra of some rosane diterpenoids. Phytochemistry 1978; 17: 572-573
  • 24 Naganuma M, Nishida M, Kuramochi K, Sugawara F, Yoshida H, Mizushina Y. 1-Deoxyrubralactone, a novel specific inhibitor of families X and Y of eukaryotic DNA polymerases from a fungal strain derived from sea algae. Biorg Med Chem 2008; 16: 2939-2944
  • 25 Kimura Y, Yoshinari T, Koshino H, Fujioka S, Okada K, Shimada A. Rubralactone, rubralides A, B and C, and rubramin produced by Penicillium rubrum. Biosci Biotechnol Biochem 2007; 71: 1896-1901
  • 26 Onocha PA, Okorie DA, Connolly JD, Roycroft DS. Monoterpene diol, iridoid glucoside and dibenzo-α-pyrone from Anthocleista djalonensis. Phytochemistry 1995; 40: 1183-1189
  • 27 Kwon HC, Zee SD, Cho SY, Choi SU, Lee KR. Cytotoxic ergosterols from Paecilomyces sp J300. Arch Pharmacal Res 2002; 25: 851-855
  • 28 Moon DO, Asami Y, Long H, Jang JH, Bae EY, Kim BY, Choi YH, Kang CH, Ahn JS, Kim GY. Verrucarin A sensitizes TRAIL-induced apoptosis via the upregulation of DR5 in an eIF2alpha/CHOP-dependent manner. Toxicol In Vitro 2013; 27: 257-263
  • 29 Jayasooriya RG, Moon DO, Yun SG, Choi YH, Asami Y, Kim MO, Jang JH, Kim BY, Ahn JS, Kim GY. Verrucarin A enhances TRAIL-induced apoptosis via NF-kappaB-mediated Fas overexpression. Food Chem Toxicol 2013; 55: 1-7
  • 30 Wu W, Ruan H. Triterpenoids and lignans from the stems of Schisandra glaucescens. Nat Prod Res 2019; 33: 328-334