TRAIL-sensitizing Cytochalasins from the Endophytic Fungus Phoma multirostrata

ABSTRACT

Seven undescribed cytochalasins, multirostratins K – Q (2–8), together with one known analogue, cytochalasin Z3 (1), were isolated from the culture of Phoma multirostrata XJ-2-1, an endophytic fungus obtained from the root of Parasenecio albus. Their structures with absolute configurations were determined by 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), electronic circular dichroism (ECD), single-crystal X-ray crystallography, and chemical methods. The structure of ascochalasin was revised from Δ ¹³ to Δ ²¹ by detailed analysis of the NMR data and by comparison with the data for 7. In a TRAIL (tumor necrosis factor related apoptosis inducing ligand)-resistance-overcoming experiment, co-treatment of 2 or 6 with TRAIL reduced the cell viability of A549 cells by 30.3% and 27.5% at 10 µM, respectively.

Key words

Didymellaceae - Phoma multirostrata - Asteraceae - Parasenecio albus - Cytochalasins - TRAIL-resistance-overcoming activities

• References

• 1 Scherlach K, Boettger D, Remme N, Hertweck C. The chemistry and biology of cytochalasans. Nat Prod Rep 2010; 27: 869-886
• 2 Li H, Xiao J, Gao YQ, Tang JJ, Zhang AL, Gao JM. Chaetoglobosins from Chaetomium globosum, an endophytic fungus in Ginkgo biloba, and their phytotoxic and cytotoxic activities. J Agric Food Chem 2014; 62: 3734-3741
• 3 Gao WX, Sun WG, Li FL, Chai CW, He Y, Wang JP, Xue YB, Chen CM, Zhu HC, Hu ZX, Zhang YH. Armochaetoglasins A–I: cytochalasan alkaloids from fermentation broth of Chaetomium globosum TW1-1 by feeding L-tyrosine. Phytochemistry 2018; 156: 106-115
• 4 Mendes G, Oliveira DD, Kohlhoff M, Rosa CA, Alves TMDA, Zani CL, Rosa LH, Johann S, Cota BB. Alkaloidal metabolites from Aspergillus felis and their activities against Paracoccidioides brasiliensis . Phytochem Lett 2016; 17: 28-35
• 5 Chen CM, Zhu HC, Wang JP, Yang J, Li XN, Wang J, Chen KL, Wang YY, Luo ZW, Yao GM, Xue YB, Zhang YH. Armochaetoglobins K–R, anti-HIV pyrrole-based cytochalasans from Chaetomium globosum TW1-1. Eur J Org Chem 2015; 2015: 3086-3094
• 6 Makioka A, Kumagai M, Kobayashi S, Takeuchi T. Different effects of cytochalasins on the growth and differentiation of Entamoeba invadens . Parasitol Res 2004; 93: 594-597
• 7 Park JY, Ji YS, Zhu H, Zhang Y, Park DH, Kim YJ, Yoo HH, Kang KS. Anti-angiogenic effect of asperchalasine a via attenuation of VEGF signaling. Biomolecules 2019; 9: 358
• 8 Hu Z, Ye Y, Zhang Y. Large-scale culture as a complementary and practical method for discovering natural products with novel skeletons. Nat Prod Rep 2021; 38: 1775-1793
• 9 Chen ZM, Chen HP, Li Y, Feng T, Liu JK. Cytochalasins from cultures of endophytic fungus Phoma multirostrata EA-12. J Antibiot 2015; 68: 23-26
• 10 Peng X, He Y, Gao Y, Duan F, Chen J, Ruan H. Cytochalasins from an endophytic fungus Phoma multirostrata XJ-2-1 with cell cycle arrest and TRAIL-resistance-overcoming activities. Bioorg Chem 2020; 104: 104317
• 11 Zhu H, Chen C, Tong Q, Zhou Y, Ye Y, Gu L, Zhang Y. Progress in the chemistry of cytochalasans. Prog Chem Org Nat Prod 2021; 114: 1-134
• 12 Zhu H, Chen C, Tong Q, Yang J, Wei G, Xue Y, Wang J, Luo Z, Zhang Y. Asperflavipine A: A cytochalasan heterotetramer uniquely defined by a highly complex tetradecacyclic ring system from Aspergillus flavipes QCS12. Angew Chem Int Ed Engl 2017; 56: 5242-5246
• 13 Jiang T, Wang M, Li L, Si J, Song B, Zhou C, Yu M, Wang X, Zhang Y, Ding G, Zou Z. Overexpression of the global regulator LaeA in Chaetomium globosum leads to the biosynthesis of chaetoglobosin Z. J Nat Prod 2016; 79: 2487-2494
• 14 Chen C, Zhu H, Li XN, Yang J, Wang J, Li G, Li Y, Tong Q, Yao G, Luo Z, Xue Y, Zhang Y. Armochaeglobines A and B, two new indole-based alkaloids from the arthropod-derived fungus Chaetomium globosum . Org Lett 2015; 17: 644-647
• 15 Yan BC, Wang WG, Hu DB, Sun X, Kong LM, Li XN, Du X, Luo SH, Liu Y, Li Y, Sun HD, Pu JX. Phomopchalasins A and B, two cytochalasans with polycyclic-fused skeletons from the endophytic fungus Phomopsis sp. shj2. Org Lett 2016; 18: 1108-1111
• 16 Peng XG, Duan FF, He YZ, Gao Y, Chen J, Chang JL, Ruan HL. Ergocytochalasin A, a polycyclic merocytochalasan from an endophytic fungus Phoma multirostrata XJ-2-1. Org Biomol Chem 2020; 18: 4056-4062
• 17 Evidente A, Andolfi A, Vurro M, Zonno MC, Motta A. Cytochalasins Z1, Z2 and Z3, three 24-oxa[14]cytochalasans produced by Pyrenophora semeniperda . Phytochemistry 2002; 60: 45-53
• 18 Aldridge DC, Armstrong JJ, Speake RN, Turner WB. Cytochalasins, a new class of biologically active mold metabolites. Chem Commun 1967; 1: 26-27
• 19 Kim EL, Li JL, Dang HT, Hong J, Lee CO, Kim DK, Yoon WD, Kim E, Liu Y, Jung JH. Cytotoxic cytochalasins from the endozoic fungus Phoma sp. of the giant jellyfish Nemopilema nomurai . Bioorg Med Chem Lett 2012; 22: 3126-3129
• 20 Yang MH, Gu ML, Han C, Guo XJ, Yin GP, Kong LY. Aureochaeglobosins A–C, three [4 + 2] adducts of chaetoglobosin and aureonitol derivatives from Chaetomium globosum . Org Lett 2018; 20: 3345-3348
• 21 Binder M, Tamm C. Proxiphomin und Protophomin, zwei neue Cytochalasane. Helv Chim Acta 1973; 56: 246
• 22 Skellam E. The biosynthesis of cytochalasans. Nat Prod Rep 2017; 34: 1252-1263
• 23 Capasso R, Evidente A, Ritieni A, Randazzo G, Vurro M, Bottalico A. Ascochalasin, a new cytochalasin from Ascochyta heteromorpha . J Nat Prod 1988; 51: 567-571