Marine Bacteria, XLVII^[*] – Psychrotolerant Bacteria from Extreme Antarctic Habitats as Producers of Rare Bis- and Trisindole Alkaloids

Abstract

From the gastrointestinal tract of a fish dredged near the South Orkney Islands in Antarctica, we isolated the psychrotolerant bacterial strain T262, which belongs to the species Vibrio splendidus. Investigation of this strain led to the isolation of a series of 15 bis- and trisindole derivatives. Among them, six new indole alkaloids, namely, turbomycin C [4′-n-butoxyphenyl-bis(1H-indol-3-yl)methane, 1a], turbomycin D [4′-n-propoxyphenyl-bis(1H-indol-3-yl)methane, 1b], turbomycin E [4′-ethoxyphenyl-bis(1H-indol-3-yl)methane, 1c], turbomycin F [4′-methoxy-3′,5′-dinitrophenyl-bis(1H-indol-3-yl)methane, 2], trisindolal (3a), and 4-(1H-indol-3-yl-sulfanyl)phenol (4). Another new bisindole derivative elucidated as 2-(indol-3-ylmethyl)-indol-3-ylethanol (7a) was obtained together with six known compounds from the psychrotolerant Arthrobacter psychrochitiniphilus strain T406, isolated from the excrement of penguins. Some of the isolated compounds showed activity against both gram-positive and gram-negative bacteria at 10 µg/paper disk. Trisindolal (3a) was active against the peronosporomycetes Botrytis cinerea and Phytophthora infestans, and some of the indole derivatives indicated promising cytotoxicity towards human tumor cell lines. By exhibiting a mean IC₅₀ of 0.45 µg/mL (1.17 µM), trisindolal (3a) showed pronounced potency and selectivity in a panel of 11 human tumor cell lines derived from 10 different tumor histotypes.

Key words

Vibrio splendidus - Vibrionaceae - Arthrobacter psychrochitiniphilus - Micrococcaceae - trisindoles - bisindoles - Antarctic bacteria - psychrotolerant bacteria

^* Marine Bacteria, XLVI: Xie Z, Liu B, Wang H, Yang S, Zhang H, Wang Y, Ji N, Qin S, Laatsch H. Kiamycin, a unique cytotoxic angucyclinone derivative from a marine Streptomyces sp. Marine Drugs 2012; 10: 551–558

• References

• 1 Veale CGL, Davies-Coleman MT. Marine bi-, bis-, and trisindole alkaloids. Alkaloids Chem Biol 2014; 73: 1-64
• 2 Ballantine JA, Barrett CB, Beer RJS, Eardley S, Robertson A, Shaw BL, Simpson TH. The chemistry of bacteria. Part VII. The structure of violacein. J Chem Soc 1958; 755-760
• 3 Omura S, Sasaki Y, Iwai Y, Takeshima H. Staurosporine, a potentially important gift from a microorganism. J Antibiot (Tokyo) 1995; 48: 535-548
• 4 Rüegg UT, Burgess GM. Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases. Trends Pharmacol Sci 1989; 10: 218-220
• 5 Bush J, Long BH, Catino J, Bradner WT, Tomita K. Production and biological activity of rebeccamycin, a novel antitumor agent. J Antibiot (Tokyo) 1987; 40: 668-678
• 6 Nettleton D, Doyle T, Krishnan B, Matsumoto G, Clardy J. Isolation and structure of rebeccamycin, a new antitumor antibiotic from Nocardia aerocoligenes . Tetrahedron Lett 1985; 26: 4011-4014
• 7 Bailly C, Riou JF, Colson P, Houssier C, Rodrigues-Pereira E, Prudhomme M. DNA cleavage by topoisomerase I in the presence of indolocarbazole derivatives of rebeccamycin. Biochemistry 1997; 36: 3917-3929
• 8 Arai H, Masuda K, Kiriyama N, Nitta K, Yamamoto Y, Shimizu S. Metabolic products of Aspergillus terreus. IV. Metabolites of the Strain IFO 8835. (2). The isolation and chemical structure of indolyl benzoquinone pigments. Chem Pharm Bull 1981; 29: 961-969
• 9 He J, Wijeratne EMK, Bashyal BP, Zhan J, Seliga CJ, Liu MX, Pierson EE, Pierson LS, VanEtten HD, Gunatilaka AAL. Cytotoxic and other metabolites of Aspergillus inhabiting the rhizosphere of Sonoran desert plants. J Nat Prod 2004; 67: 1985-1991
• 10 Bifulco G, Bruno I, Minale L, Riccio R, Calignano A, Debitus C. (±)-Gelliusines A and B, two diastereomeric brominated tris-indole alkaloids from a deep water New Caledonian marine sponge. J Nat Prod 1994; 57: 1294-1299
• 11 Bifulco G, Bruno I, Riccio R, Lavayre J, Bourdy G. Further brominated bis- and tris-indole alkaloids from the deep-water New Caledonian marine sponge Orina sp. J Nat Prod 1995; 58: 1254-1260
• 12 Veluri R, Oka I, Wagner-Döbler I, Laatsch H. New indole alkaloids from the North Sea bacterium Vibrio parahaemolyticus Bio249. J Nat Prod 2003; 66: 1520-1523
• 13 Laatsch H. AntiBase 2014, a data base for rapid dereplication and structure determination of microbial natural products. Weinheim, Germany: Wiley VCH; 2014
• 14 Yan X, Tang XX, Chen L, Yi ZW, Fang MJ, Wu Z, Qiu YK. Two new cytotoxic indole alkaloids from a deep-sea sediment derived metagenomic clone. Mar Drugs 2014; 12: 2156-2163
• 15 Noland WE, Hammer CF. Mixed indole dimers, trimers, and acyl derivatives. J Org Chem 1960; 25: 1525-1535
• 16 Matsumoto M, Nagaoka K, Ishizeki S, Yokoi K, Nakajima T. Novel physiologically active substance SS43405E and production thereof. Kokai Tokkyo Koho JP 61189280A, 1986
• 17 Li X, Lee SO, Safe S. Structure-dependent activation of NR4A2 (Nurr1) by 1,1-bis(3′-indolyl)-1-(aromatic) methane analogs in pancreatic cancer cells. Biochem Pharmacol 2012; 83: 1445-1455
• 18 Khazaei A, Zolfigol MA, Faal-Rastegar T. Ionic liquid tributyl (carboxymethyl) phosphonium bromide as an efficient catalyst for the synthesis of bis(indolyl)methanes under solvent-free conditions. Chem Pharm Bull (Tokyo) 2013; 37: 617-619
• 19 Abdul Qayum M, Srinivas P, Uday Kumar N. Synthesis of bis(indolyl)methanes by using ferric triflate as a catalyst. Chem Biol Interface 2013; 3: 334-338
• 20 Al-Zereini W, Schuhmann I, Laatsch H, Helmke E, Anke H. New aromatic nitro compounds from Salegentibacter sp. T436, an Arctic Sea ice bacterium: taxonomy, fermentation, isolation and biological activities. J Antibiot (Tokyo) 2007; 60: 301-308
• 21 Shangguan D, Jiang R, Li B, Xiao C, Wu J. [Production, isolation and structure elucidation of novel isoflavonoid compound K3-D4, K3-D5, K3-D6]. Zhongguo Kangshengsu Zazhi 1999; 24: 254-257
• 22 ACD/NMR Predictor. 2002. Advanced Chemistry Development, Inc. Toronto, Ontario, Canada. Available at: http://www.acdlabs.com/company/media/pr/100330_nmrproc.php Accessed June 1, 2016
• 23 Prasad CD, Kumar S, Sattar M, Adhikary A, Kumar S. Metal free sulfenylation and bis-sulfenylation of indoles: persulfate mediated synthesis. Org Biomol Chem 2013; 11: 8036-8040
• 24 Pal B, Giri VS, Jaisankar P. First indium trichloride catalyzed self-addition of indoles: One pot synthesis of indolylindolines. Catal Commun 2005; 6: 711-715
• 25 Cai SX, Li DH, Zhu TJ, Wang FP, Xiao X, Gu QQ. Two new indole alkaloids from the marine-derived bacterium Aeromonas sp. CB101. Helv Chim Acta 2010; 93: 791-794
• 26 Feldl C, Møller P, Otte J, Sørensen H. Micellar electrokinetic capillary chromatography for determination of indolyl glucosinolates and transformation products thereof. Anal Biochem 1994; 217: 62-69
• 27 Hardeland R. Melatonin metabolism in the central nervous system. Curr Neuropharmacol 2010; 8: 168-181
• 28 White RH. Indole-3-acetic acid and 2-(indol-3-ylmethyl) indol-3-yl acetic acid in the thermophilic archaebacterium Sulfolobus acidocaldarius . J Bacteriol 1987; 169: 5859-5860
• 29 Wille G, Mayser P, Thoma W, Monsees T, Baumgart A, Schmitz HJ, Schrenk D, Polborn K, Steglich W. Malassezin – A novel agonist of the arylhydrocarbon receptor from the yeast Malassezia furfur . Bioorg Med Chem 2001; 9: 955-960
• 30 Dengler WA, Schulte J, Berger DP, Mertelsmann R, Fiebig HH. Development of a propidium iodide fluorescence assay for proliferation and cytotoxicity assays. Anticancer Drugs 1995; 6: 522-532
• 31 Roth T, Burger AM, Dengler W, Willmann H, Fiebig HH. Human tumor cell lines demonstrating the characteristics of patient tumors as useful models for anticancer drug screening. In: Fiebig HH, Burger AM, editors Relevance of tumor models for anticancer drug development. Basel, Switzerland: Karger; 1999: 145-157
• 32 Fiebig HH, Dengler WA, Roth T. Human tumor xenografts: predictivity, characterization and discovery of new anticancer agents. In: Fiebig HH, Burger AM, editors Relevance of tumor models for anticancer drug development. Basel, Switzerland: Karger; 1999: 29-50
• 33 Fiebig HH, Berger DP, Dengler WA, Wallbrecher E, Winterhalter BR. Combined in vitro/in vivo test procedure with human tumor xenografts for new drug development. In: Fiebig HH, Berger DP, editors Immunodeficient mice in oncology. International Symposium, Freiburg, November 1990, vol. 42. Basel, Switzerland: Karger; 1992: 321-351
• 34 Baumann P, Baumann L, Bang SS, Woolkalis MJ. Reevaluation of the taxonomy of Vibrio, Beneckea, and Photobacterium: abolition of the genus Beneckea . Curr Microbiol 1980; 4: 127-132
• 35 Wang F, Gai Y, Chen M, Xiao X. Arthrobacter psychrochitiniphilus sp. nov., a psychrotrophic bacterium isolated from Antarctica. Int J Syst Evol Microbiol 2009; 59: 2759-2762