Delitpyrones: α-Pyrone Derivatives from a Freshwater Delitschia sp.

José Rivera-Chávez; Tamam El-Elimat; Jacklyn M. Gallagher; Tyler N. Graf; Jacques Fournier; Gati K. Panigrahi; Gagan Deep; Rick L. Bunch; Huzefa A. Raja; Nicholas H. Oberlies

doi:10.1055/a-0654-5850

Planta Medica, Table of Contents

Planta Med 2019; 85(01): 62-71
DOI: 10.1055/a-0654-5850

Natural Product Chemistry and Analytical Studies

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Delitpyrones: α-Pyrone Derivatives from a Freshwater Delitschia sp.

José Rivera-Chávez

¹Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina, USA

⁶Current address: Department of Natural Products, Instituto de Química, Universidad Nacional Autónoma de México, Ciudad de México, México

,

Tamam El-Elimat

²Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan

,

Jacklyn M. Gallagher

¹Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina, USA

,

Tyler N. Graf

¹Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina, USA

,

Jacques Fournier

³Los Muros, Rimont, France

,

Gati K. Panigrahi

⁴Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest Baptist Medical Center & Wake Forest School of Medicine, Winston-Salem, North Carolina, USA

,

Gagan Deep

⁴Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest Baptist Medical Center & Wake Forest School of Medicine, Winston-Salem, North Carolina, USA

,

Rick L. Bunch

⁵Department of Geography, Environment, and Sustainability, University of North Carolina at Greensboro, Greensboro, North Carolina, USA

,

Huzefa A. Raja

¹Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina, USA

,

Nicholas H. Oberlies

¹Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina, USA

› Author Affiliations

Abstract

In research focused on the discovery of new chemical diversity from freshwater fungi, a peak library was built and evaluated against a prostate cancer cell line, E006AA-hT, which was derived from an African American, as this population is disproportionately affected by prostate cancer. The chemical study of the bioactive sample accessioned as G858 (Delitschia sp.) led to the isolation of eight new α-pyrone derivatives (1 – 7, and 11), as well as the new 3S*,4S*-7-ethyl-4,8-dihydroxy-3,6-dimethoxy-3,4-dihydronaphthalen-1(2H)-one (15). In addition, the known compounds 5-(3-S-hydroxybutyl)-4-methoxy-6-methyl-2H-pyran-2-one (8), 5-(3-oxobutyl)-4-methoxy-6-methyl-2H-pyran-2-one (9), pyrenocine I (10), 5-butyl-6-(hydroxymethyl)-4-methoxy-2H-pyran-2-one (12), sporidesmin A (13), 6-ethyl-2,7-dimethoxyjuglone (14), artrichitin (16), and lipopeptide 15G256ε (17) were also obtained. The structures of the new compounds were elucidated using a set of spectroscopic (NMR) and spectrometric (HRMS) methods. The absolute configuration of the most abundant member of each subclass of compounds was assigned through a modified Mosherʼs ester method. For 15, the relative configuration was assigned based on analysis of ³ J values. Compounds 1, 2, 5 – 14, 16, and 17 were evaluated against the cancer cell line E006AA-hT under hypoxic conditions, where compound 13 inhibited cell proliferation at a concentration of 2.5 µM.

Key words

peak library - prostate cancer - cell proliferation - freshwater fungi - delitpyrones - Delitschia sp.

Full Text

References

References
1 Hawksworth DL, Lücking R. Fungal diversity revisited: 2.2 to 3.8 million species. Microbiol Spectr 2017; 5: 1-17
2 Choi J, Kim SH. A genome tree of life for the Fungi kingdom. Proc Natl Acad Sci U S A 2017; 114: 9391-9396
3 Shearer CA, Raja HA. Freshwater ascomycetes database. Available at: http://fungi.life.illinois.edu/ Accessed January 14, 2018
4 Cai L, Hu DM, Liu F, Hyde KD, Gareth-Jones E. The molecular Phylogeny of freshwater Sordariomycetes and Discomycetes. In: Jones EBG, Hyde KD, Pang KL. eds. Freshwater Fungi and fungal-like Organisms. Berlin: De Gruyter; 2014: 47-72
5 Wong MKM, Goh TK, Hodgkiss IJ, Hyde KD, Ranghoo VM, Tsui CKM, Ho WH, Wong WSW, Yuen TK. Role of fungi in freshwater ecosystems. Biodivers Conserv 1998; 7: 1187-1206
6 Hernández-Carlos B, Gamboa-Angulo MM. Metabolites from freshwater aquatic microalgae and fungi as potential natural pesticides. Phytochem Rev 2011; 10: 261-286
7 Shearer CA, Descals E, Kohlmeyer B, Kohlmeyer J, Marvanová L, Padgett D, Porter D, Raja HA, Schmit JP, Thorton HA. Fungal biodiversity in aquatic habitats. Biodivers Conserv 2007; 16: 49-67
8 Paguigan ND, Raja HA, Day CS, Oberlies NH. Acetophenone derivatives from a freshwater fungal isolate of recently described Lindgomyces madisonensis (G416). Phytochemistry 2016; 126: 59-65
9 El-Elimat T, Raja HA, Day CS, Chen WL, Swanson SM, Oberlies NH. Greensporones: resorcylic acid lactones from an aquatic Halenospora sp. J Nat Prod 2014; 77: 2088-2098
10 El-Elimat T, Raja HA, Figueroa M, Falkinham 3rd JO, Oberlies NH. Isochromenones, isobenzofuranone, and tetrahydronaphthalenes produced by Paraphoma radicina, a fungus isolated from a freshwater habitat. Phytochemistry 2014; 104: 114-120
11 Ainsworth GC. Ainsworth & Bisbyʼs Dictionary of the Fungi. Wallingtonford, CT: Cabi; 2008
12 Luo JG, Wang XB, Xu YM, UʼRen JM, Arnold AE, Kong LY, Gunatilaka AAL. Delitschiapyrone A, a pyrone-naphthalenone adduct bearing a new pentacyclic ring system from the leaf-associated fungus Delitschia sp. FL1581. Org Lett 2014; 16: 5944-5947
13 Jayanetti DR, Li Y, Bartholomeusz GA, Bills GF, Gloer JB. Benzophenone and fimetarone derivatives from the coprophilous fungus Delitschia confertaspora . J Nat Prod 2017; 80: 707-712
14 Huang FW, Mosquera JM, Garofalo A, Oh C, Baco M, Amin-Mansour A, Rabasha B, Bahl S, Mullane SA, Robinson BD, Aldubayan S, Khani F, Karir B, Kim E, Chimene-Weiss J, Hofree M, Romanel A, Osborne JR, Kim JW, Azabdaftari G, Woloszynska-Read A, Sfanos K, De Marzo AM, Demichelis F, Gabriel S, Van Allen EM, Mesirov J, Tamayo P, Rubin MA, Powell IJ, Garraway LA. Exome sequencing of African-American prostate cancer reveals loss-of-function ERF mutations. Cancer Discov 2017; 7: 973-983
15 Panigrahi GK, Deep G. Exosomes-based biomarker discovery for diagnosis and prognosis of prostate cancer. Front Biosci (Landmark Ed) 2017; 22: 1682-1696
16 Deep G, Panigrahi GK. Hypoxia-induced signaling promotes prostate cancer progression: exosomes role as messenger of hypoxic response in tumor microenvironment. Crit Rev Oncog 2015; 20: 419-434
17 El-Elimat T, Figueroa M, Ehrmann BM, Cech NB, Pearce CJ, Oberlies NH. High-resolution MS, MS/MS, and UV database of fungal secondary metabolites as a dereplication protocol for bioactive natural products. J Nat Prod 2013; 76: 1709-1716
18 Paguigan ND, El-Elimat T, Kao D, Raja HA, Pearce CJ, Oberlies NH. Enhanced dereplication of fungal cultures via use of mass defect filtering. J Antibiot 2017; 70: 553-561
19 Karakashev SV, Reginato MJ. Progress toward overcoming hypoxia-induced resistance to solid tumor therapy. Cancer Manag Res 2015; 7: 253-264
20 Tredan O, Galmarini CM, Patel K, Tannock IF. Drug resistance and the solid tumor microenvironment. J Natl Cancer Inst 2007; 99: 1441-1454
21 Rivera-Chávez J, Raja HA, Graf TN, Burdette JE, Pearce CJ, Oberlies NH. Biosynthesis of fluorinated peptaibols using a site-directed building block incorporation approach. J Nat Prod 2017; 80: 1883-1892
22 Metwaly AM, Wanas AS, Radwan MM, Ross SA, ElSohly MA. New α-pyrone derivatives from the endophytic fungus Embellisia sp. Med Chem Res 2017; 26: 1796-1800
23 Metwaly AM, Fronczek FR, Ma G, Kadry HA, El-Hela AA, Mohammad AI, Cutler SJ, Ross SA. Antileukemic α-pyrone derivatives from the endophytic fungus Alternaria phragmospora . Tetrahedron Lett 2014; 55: 3478-3481
24 Hashida J, Niitsuma M, Iwatsuki M, Mori M, Ishiyama A, Namatame M, Nishihara-Tsukashima A, Nonaka K, Ui H, Masuma R, Otoguro K, Yamada H, Shiomi K, Ōmura S. Pyrenocine I, a new pyrenocine analog produced by Paecilomyces sp. FKI-3573. J Antibiot (Tokyo) 2010; 63: 559
25 Dingley JM, Done J, Taylor A, Russell DW. The production of sporidesmin and sporidesmolides by wild isolates of Pithomyces chartarum in surface and in submerged culture. Microbiology 1962; 29: 127-135
26 Sun R, Gao YX, Shen KZ, Xu YB, Wang CR, Liu HY, Dong JY. Antimicrobial metabolites from the aquatic fungus Delitschia corticola . Phytochem Lett 2011; 4: 101-105
27 Vijayakumar EKS, Roy K, Chatterjee S, Deshmukh SK, Ganguli BN, Fehlhaber HW, Kogler H. Arthrichitin. A new cell wall active metabolite from Arthrinium phaeospermum . J Org Chem 1996; 61: 6591-6593
28 Schlingmann G, Milne L, Williams DR, Carter GT. Cell wall active antifungal compounds produced by the marine fungus Hypoxylon oceanicum LL-15G256. II. Isolation and structure determination. J Antibiot (Tokyo) 1998; 51: 303-316
29 Hoye TR, Jeffrey CS, Shao F. Mosher ester analysis for the determination of absolute configuration of stereogenic (chiral) carbinol carbons. Nat Protocols 2007; 2: 2451-2458
30 Pavia DL, Lampman GM, Kriz GS, Vyvyan JA. Introduction to spectroscopy. 5th ed. Stamford, Connecticut: Cengage Learning; 2015: 359
31 Bentley R, Banach WJ, McInnes AG, Walter JA. 6-Ethyl-5-hydroxy-2,7-dimethoxy-1,4-naphthoquinone from Hendersonula toruloidea: A biosynthetic study using ¹³C labels detected by nuclear magnetic resonance and ¹⁴C tracers. Bioorg Chem 1981; 10: 399-411
32 Howe R, Moore RH. 6-ethyl-5-hydroxy-2,7-dimethoxynaphthoquinone, a metabolite of Hendersonula toruloidea Nattrass. Experientia 1969; 25: 474
33 Pittayakhajonwut P, Sohsomboon P, Dramae A, Suvannakad R, Lapanun S, Tantichareon M. Antimycobacterial substances from Phaeosphaeria sp. BCC8292. Planta Med 2008; 74: 281-286
34 Vilgalys R, Hester M. Rapid genetic identification and mapping of enzymatically amplified ribosomal DNA from several Cryptococcus species. J Bacteriol 1990; 172: 4238-4246
35 Rehner SA, Samuels GJ. Molecular systematics of the Hypocreales: a teleomorph gene phylogeny and the status of their anamorphs. Can J Bot 1995; 73: S816-S823
36 Mugambi G, Huhndorf S. Molecular phylogenetics of Pleosporales: Melanommataceae and Lophiostomataceae re-circumscribed (Pleosporomycetidae, Dothideomycetes, Ascomycota). Stud Mycol 2009; 64: 103-121
37 Raja HA, Miller AN, Pearce CJ, Oberlies NH. Fungal identification using molecular tools: a primer for the natural products research community. J Nat Prod 2017; 80: 756-770
38 Calaça F, Delpont M, Xavier-Santos S. Delitschia gigaspora var. pescanii: a new variety of coprophilous fungus from Brazil. Mycosphere 2015; 6: 122-126
39 Luck-Allen ER, Cain RF. Additions to the genus Delitschia . Can J Bot 1975; 53: 1827-1887
40 Hyde KD, Steinke TS. Two new species of Delitschia from submerged wood. Mycoscience 1996; 37: 99-102
41 Wallace EM, Rizzi JP, Han G, Wehn PM, Cao Z, Du X, Cheng T, Czerwinski RM, Dixon DD, Goggin BS, Grina JA, Halfmann MM, Maddie MA, Olive SR, Schlachter ST, Tan H, Wang B, Wang K, Xie S, Xu R, Yang H, Josey JA. A small-molecule antagonist of HIF2α is efficacious in preclinical models of renal cell carcinoma. Cancer Res 2016; 76: 5491-5500

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