Bioactive Secondary Metabolites from the Endophytic Fungi Alternaria sp.

https://doi.org/10.22146/ijc.68922

Antonius Rolling Basa Ola(1*), Dodi Darmakusuma(2), Luther Kadang(3), Amor Tresna Karyawati(4), Sherly Monitha Febriani Ledoh(5), Imanuel Gauru(6), Pius Dore Ola(7), Suwari Suwari(8), Henderiana Laura Loiusa Belli(9)

(1) Department of Chemistry, Faculty of Science and Engineering, Universitas Nusa Cendana, Jl. Adisucipto, Penfui-Kupang 85118, NTT, Indonesia; Integrated Research Center (Bioscience) Laboratory, Nusa Cendana University, Jl. Adisucipto, Penfui-Kupang 85118, NTT, Indonesia
(2) Department of Chemistry, Faculty of Science and Engineering, Universitas Nusa Cendana, Jl. Adisucipto, Penfui-Kupang 85118, NTT, Indonesia
(3) Department of Chemistry, Faculty of Science and Engineering, Universitas Nusa Cendana, Jl. Adisucipto, Penfui-Kupang 85118, NTT, Indonesia
(4) Department of Biology, Faculty of Science and Engineering, Nusa Cendana University, Jl. Adisucipto, Penfui-Kupang 85118, NTT, Indonesia
(5) Department of Chemistry, Faculty of Science and Engineering, Universitas Nusa Cendana, Jl. Adisucipto, Penfui-Kupang 85118, NTT, Indonesia
(6) Department of Chemistry, Faculty of Science and Engineering, Universitas Nusa Cendana, Jl. Adisucipto, Penfui-Kupang 85118, NTT, Indonesia
(7) Department of Chemistry, Faculty of Science and Engineering, Universitas Nusa Cendana, Jl. Adisucipto, Penfui-Kupang 85118, NTT, Indonesia
(8) Department of Chemistry, Faculty of Science and Engineering, Universitas Nusa Cendana, Jl. Adisucipto, Penfui-Kupang 85118, NTT, Indonesia
(9) Integrated Research Center (Bioscience) Laboratory, Nusa Cendana University, Jl. Adisucipto, Penfui-Kupang 85118, NTT, Indonesia
(*) Corresponding Author

Abstract


Shifting the drug discovery from plants to microorganisms due to minimizing the ecological effects has led to the increasing work on finding bioactive metabolites from endophytic fungi, especially those isolated from medicinal plants growing in arid and semi-arid land. An endophytic fungi Alternaria sp. isolated from dry land was cultivated on solid rice media and then extracted with ethyl acetate. From the fungal ethyl acetate crude extract of Alternaria sp., compounds altertoxin I (1) and II (2), and stemphyltoxin III (3), were isolated based on the bioactivity assay. The structures of compounds 1-3 were identified using UV, NMR, and mass spectral data and compared to those spectral data reported in the literature. The absolute configuration was determined to be the same as the previous report based on the comparison with the optical rotation value. The three compounds showed strong cytotoxic activity, with altertoxin II being the most active ones having the inhibition of growth observed at 94.4% against murine lymphoma L5178Y cell line at 10 µg/mL. The activity of altertoxin II (2) was probably contributed by the epoxytetralone moiety. The finding of this study still confirms the importance of endophytic fungi as sources of bioactive molecules.


Keywords


endophytic fungi; cytotoxic; altertoxin I and II; stemphyltoxin III

Full Text:

Full Text PDF


References

[1] Rustamova, N., Bozorov, K., Efferth, T., and Yili, A., 2020, Novel secondary metabolites from endophytic fungi: Synthesis and biological properties, Phytochem. Rev., 19 (2), 425–448.

[2] Kumar, S., Aharwal, R.P., Jain, R., and Sandhu, S.S., Bioactive molecules of endophytic fungi and their potential in anticancer drug development, Curr. Pharmacol. Rep., 7 (2), 27–41.

[3] Akone, S.H., Pham, C.D., Chen, H., Ola A.R.B., Ntie-Kang, F., and Proksch, P., 2019, Epigenetic modification, co-culture and genomic methods for natural product discovery, Phys. Sci. Rev., 4 (4), 20180118.

[4] Amirzakariya, B.Z., and Shakeri, A., 2022, Bioactive terpenoids derived from plant endophytic fungi: An updated review (2011–2020), Phytochemistry, 197, 113130.

[5] Bara, R., Aly, A.H., Pretsch, A., Wray, V., Wang, B., Proksch, P., and Debbab, A., 2013, Antibiotically active metabolites from Talaromyces wortmannii, an endophyte of Aloe vera, J. Antibiot., 66 (8), 491–493.

[6] Bara, R., Zerfass, I., Aly, A.H., Goldbach-Gecke, H., Raghavan, V., Sass, P., Mándi, A., Wray, V., Polavarapu, P.L., Pretsch, A., Lin, W., Kurtán, T., Debbab, A., Brőtz-Oesterhelt, H., and Proksch, P., 2013, Atropisomeric dihydroanthracenones as inhibitors of multiresistant Staphylococcus aureus, J. Med. Chem., 56 (8), 3257–3272.

[7] Ola, A.R.B., Metboki, G., Lay, C.S., Sugi, Y., De Rozari, P., Darmakusuma, D., and Hakim, E.H., 2019, Single production of kojic acid by Aspergillus flavus and the revision of flufuran, Molecules, 24 (22), 4200.

[8] Bashyal, B.P., Wellensiek, B.P., Ramakrishnan, R., Faeth, S.H., Ahmad, N., and Gunatilaka, A.A.L., 2014, Altertoxins with potent anti-HIV activity from Alternaria tenuissima QUE1Se, a fungal endophyte of Quercus emoryi, Bioorg. Med. Chem., 22 (21), 6112–6116.

[9] Ola, A.R.B., Debbab, A., Kurtán, T., Brötz-Oesterhelt, H., Aly, A.H., and Proksch, P., 2014, Dihydroanthracenone metabolites from the endophytic fungus Diaporthe melonis isolated from Annona squamosa, Tetrahedron Lett., 55 (20), 3147–3150.

[10] Ola, A.R.B., Debbab, A., Aly, A.H., Mandi, A., Zerfass, I., Hamacher, A., Kassack, M.U., Brötz-Oesterhelt, H., Kurtan, T., and Proksch, P., 2014, Absolute configuration and antibiotic activity of neosartorin from the endophytic fungus Aspergillus fumigatiaffinis, Tetrahedron Lett., 55 (5), 1020–1023.

[11] Chen, H., Daletos, G., Okoye, F., Lai, D., Dai, H., and Proksch, P., 2015, A new cytotoxic cytochalasin from the endophytic fungus Trichoderma harzianum, Nat. Prod. Commun., 10 (4), 585–587.

[12] Aly, A.H., Debbab, A., and Proksch, P., 2013, Fungal endophytes - secret producers of bioactive plant metabolites, Pharmazie, 68, 499–505.

[13] Turbyville, T.J., Wijeratne, E.M.K., Liu, M.X., Burns, A.M., Seliga, C.J., Luevano, L.A., David, C.L., Faeth, S.H., Whitesell, L., and Gunatilaka, A.A.L., 2006, Search for Hsp90 inhibitors with potential anticancer activity: Isolation and SAR studies of radicicol and monocillin I from two plant-associated fungi of the Sonoran Desert, J. Nat. Prod., 69 (2), 178–184.

[14] Verekar, S.A., Mishra, P.D., Sreekumar, E.S., Deshmukh, S.K., Fiebig, H.H., Kelter, G., and Maier, A., 2014, Anticancer activity of new depsipeptide compound isolated from an endophytic fungus, J. Antibiot., 67 (10), 697–701.

[15] Okuno, T., Natsume, I., Sawai, K., Sawamura, K., Furusaki, A., and Matsumoto, T., 1983, Structure of antifungal and phytotoxic pigments produced by Alternaria sps., Tetrahedron Lett., 24 (50), 5653–5656.

[16] Stack, M.E., Mazzola, E.P., Page, S.W., Pohland, A.E., Highet, R.J., Tempesta, M.S., and Corley, D.G., 1986, Mutagenic perylenequinone metabolites of Alternaria alternate: Altertoxins I, II, and III, J. Nat. Prod., 49 (5), 866–871.

[17] Stack, M.E., and Mazzola, E.P., 1989, Stemphyltoxin III from Altenaria alternata, J. Nat. Prod., 52 (2), 426–427.

[18] Schwarz, C., Tiessen, C., Kreutzer, M., Stark, T., Hofmann, T., and Marko, D., 2012, Characterization of a genotoxic impact compound in Alternaria alternata infested rice as altertoxin II, Arch. Toxicol., 86 (12), 1911–1925.

[19] Podlech, J., Fleck, S.C., Metzler, M., Bürck, J., and Ulrich, A.S., 2014, Determination of the absolute configuration of perylene quinone-derived mycotoxins by measurement and calculation of electronic circular dichroism spectra and specific rotations, Chem. - Eur. J., 20 (36), 11463–11470.

[20] Wu, W.B., Yue, G.C., Huang, Q.L., Sun, L.L., and Zhang, W., 2014, A new compound from an endophytic fungus Alternaria tenuissima, J. Asian Nat. Prod. Res., 16 (7), 777–782.

[21] Robles, A.J., Dai, W., Haldar, S., Ma, H., Anderson, V.M., Overacker, R.D., Risinger, A.L., Loesgen, S., Houghton, P.J., Cichewicz, R.H., and Mooberry, S.L., 2021, Altertoxin II, a highly effective and specific compound against Ewing sarcoma, Cancers, 13 (24), 6176.



DOI: https://doi.org/10.22146/ijc.68922

Article Metrics

Abstract views : 3605 | views : 2268


Copyright (c) 2022 Indonesian Journal of Chemistry

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

 


Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

Web
Analytics View The Statistics of Indones. J. Chem.