Abstract
Medicinal plants have been studied for potential endophytic interactions and numerous studies have provided evidence that seeds harbor diverse microbial communities, not only on their surfaces but also within the embryo. Adenosine deaminase (ADA) is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Therefore, in this study, 20 types of medicinal plant seeds were used to screen endophytic fungi with tissue homogenate and streak. In addition, 128 morphologically distinct endophyte strains were isolated and their ADA inhibitory activity determined by a spectrophotometric assay. The strain with the highest inhibitory activity was identified as Cochliobolus sp. Seven compounds were isolated from the strain using a chromatography method. Compound 3 showed the highest ADA inhibitory activity and was identified as 5-hydroxy-2-hydroxymethyl-4H-pyran-4-one, based on the results of 1H and 13C NMR spectroscopy. The results of molecular docking suggested that compound 3 binds to the active site and the nonspecific binding site of the ADA. Furthermore, we found that compound 3 is a mixed ADA inhibitor. These results indicate that endophytic strains are a promising source of ADA inhibitors and that compound 3 may be a superior source for use in the preparation of biologically active ADA inhibitor compounds used to treat cancer.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Agarwal RP (1982) Inhibitors of adenosine deaminase. Pharmacol Therapeut 17:399–429. https://doi.org/10.1016/0163-7258(82)90023-7
Ansari MM, Ahmad J, Ali M, Ansari SH (2006) 10-methyl-n-heptacosane and diglucosyldirhamnoside from the stem bark of Balanites aegyptiaca Delile. Indian J Chem Sect B 45:2154–2156. https://doi.org/10.1186/s12906-016-1369-5
Arthaud ID, Rodrigues FA, Jimenez PC et al (2012) Studies on the secondary metabolites of a Pseudoalteromonas sp. isolated from sediments collected at the northeastern coast of Brazil. Chem Biodivers 9:418–427. https://doi.org/10.1002/cbdv.201100092
Azimi R, Baharfar R (2014) ChemInform abstract: DABCO-functionalized mesoporous SBA-15: an efficient and recyclable catalyst for the synthesis of Spiro-Pyranoxindoles as antioxidant agents. Can J Chem 46(19):1163–1168(6). https://doi.org/10.1139/cjc-2014-0309
Basu M, Sanyal AK, Banerjee AB (2002) A new method of colorimetric assay of beta-lactamase suitable for estimation of beta-lactamase inhibition in crude microbial culture filtrates. Folia Microbiol 47:32–36. https://doi.org/10.1007/BF02818562
Bezerra JDP, Nascimento CCF, Barbosa RDN et al (2015) Endophytic fungi from medicinal plant Bauhinia forficata : diversity and biotechnological potential. Braz J Microbiol 46:49–57. https://doi.org/10.1590/S1517-838246120130657
Bransova J, Brtko J, Uher M, Novotny L (1995) Antileukemic activity of 4-pyranone derivatives. Int J Biochem Cell Biol 27:701–706. https://doi.org/10.1016/1357-2725(95)00031-J
Brtko J, Bransova-Bobalova JE, Eyblo V, Ivielnix M, Uheru M (2001) Kojic acid: a superior source for preparation of biological active compounds (current experience). Biomarker Environ 4:62–73
Brtko J, Rondahl L, Ficková M, Hudecová D, Eybl V, Uher M (2004) Kojic acid and its derivatives: history and present state of art. Cent Eur J Public Health 12(Suppl):S16–S18
Cristalli G, Costanzi S, Lambertucci C, Lupidi G, Vittori S, Volpini R, Camaioni E (2001) Adenosine deaminase: functional implications and different classes of inhibitors. Med Res Rev 21:105–128. https://doi.org/10.1002/1098-1128(200103)21:2<105::AID-MED1002>3.0.CO;2-U
Dobson RC, Griffin MD, Roberts SJ, Gerrard JA (2004) Dihydrodipicolinate synthase (DHDPS) from Escherichia coli displays partial mixed inhibition with respect to its first substrate, pyruvate. Biochimie 86:311–315. https://doi.org/10.1016/j.biochi.2004.03.008
Dong PJ, Zhang XG, Liu YJ, Kou F, Tang P, Su Y (2015) Rapid drug model for screening adenosine deaminase inhibitor. Chin J Mod Appl Pharm 32:1301–1305
Fickova M, Pravdova E, Rondhal L, Uher M, Brtko J (2008) In vitro antiproliferative and cytotoxic activities of novel kojic acid derivatives: 5-benzyloxy-2-selenocyanatomethyl- and 5-methoxy-2-selenocyanatomethyl-4-pyranone. J Appl Toxicol 28:554–559. https://doi.org/10.1002/jat.1300
Glader BE, Backer K, Diamond LK (1983) Elevated erythrocyte adenosine deaminase activity in congenital hypoplastic anemia. New Engl J Med 309:1486–1490. https://doi.org/10.1056/NEJM198312153092404
Glazer RI (1980) Adenosine deaminase inhibitors: their role in chemotherapy and immunosuppression. Cancer Chemother Pharmacol 4:227–235. https://doi.org/10.1007/BF00255266
Häberlein H, Tschiersch KP (1994) Triterpenoids and flavonoids from Leptospermum scoparium. Phytochemistry 35:765–768. https://doi.org/10.1016/S0031-9422(00)90601-0
Hudecová D, Jantová S, Melník M, Uher M (1996) New azidometalkojates and their biological activity. Folia Microbiol 41:473–476. https://doi.org/10.1007/BF02814660
Iaroshenko VO, Ostrovskyi D, Petrosyan A, Mkrtchyan S, Villinger A, Langer P (2011) Synthesis of fluorinated purine and 1-Deazapurine glycosides as potential inhibitors of adenosine deaminase. J Organomet Chem 76:2899–2903. https://doi.org/10.1021/jo102579g
Irene D, Chung TY, Chen BJ, Liu TH, Li FY, Tzen JT, Wang CI, Chyan CL (2012) Solution structure of a phytocystatin from Ananas comosus and its molecular interaction with papain. PLoS One 7:e47865. https://doi.org/10.1371/journal.pone.0047865
Kinoshita T, Nishio N, Sato A, Murata M (1999) Crystallization and preliminary analysis of bovine adenosine deaminase. Acta Crystallogr D Biol Crystallogr 55:2031–2032. https://doi.org/10.1107/S090744499901183X
Li J, Zhang J, Lai B, Zhao Y, Li Q (2015) Cloning, expression, and characterization of Capra hircus Golgi α-mannosidase II. Appl Biochem Biotechnol 177:1241–1251. https://doi.org/10.1007/s12010-015-1810-0
Mardanyan S, Sharoyan S, Antonyan A, Armenyan A, Cristalli G, Lupidi G (2001) Tryptophan environment in adenosine deaminase. I. Enzyme modification with N-bromosuccinimide in the presence of adenosine and EHNA analogues. BBA-Protein Struct Mol 1546:185–195. https://doi.org/10.1016/S0167-4838(01)00141-8
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30:2785–2791. https://doi.org/10.1002/jcc.21256
Nelson EB (2004) Microbial dynamics and interactions in the spermosphere. Annu Rev Phytopathol 42:271–309. https://doi.org/10.1146/annurev.phyto.42.121603.131041
Ni H, Li YH, Hao RL, Li H, Hu SQ, Li HH (2016) Identification of adenosine deaminase inhibitors from tofu wastewater and litchi peel and their synergistic anticancer and antibacterial activities with cordycepin. Int J Food Sci Technol 51:1168–1176. https://doi.org/10.1111/ijfs.13064
Nohynek GJ, Kirkland D, Marzin D, Toutain H, Leclerc-Ribaud C, Jinnai H (2004) An assessment of the genotoxicity and human health risk of topical use of kojic acid [5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one]. Food Chem Toxicol 42:93–105. https://doi.org/10.1016/j.fct.2003.08.008
Noonan M, Brady TG (1969) Purification of adenosine deaminase from bovine lung and spleen. Biochem J 115:15P–1515P. https://doi.org/10.1042/bj1150015Pa
Ono M, Honda F, Karahashi A, Kawasaki T, Miyahara K (1997) Resin glycosides. XXV. Multifidins I and II, new jalapins, from the seed of Quamoclit x multifida. Chem Pharm Bull 45:1955–1960. https://doi.org/10.1248/cpb.45.1955
Qiu P, Feng ZX, Tian JW, Lei ZC, Wang L, Zeng ZG, Chu YW, Tian YQ (2015) Diversity, bioactivities, and metabolic potentials of endophytic actinomycetes isolated from traditional medicinal plants in Sichuan, China. Chin J Nat Med 13:942–953. https://doi.org/10.1016/S1875-5364(15)30102-3
Reller LB, Weinstein MP, Petti CA (2007) Detection and identification of microorganisms by gene amplification and sequencing. Clin Infect Dis 44:1108–1114. https://doi.org/10.1086/512818
Saboury AA (2009) Enzyme inhibition and activation: a general theory. J Iran Chem Soc 6:219–229. https://doi.org/10.1007/bf03245829
Sanner MF (1999) Python: a programming language for software integration and development. J Mol Graphics Modell 17:57–61. https://doi.org/10.1016/S1093-3263(99)00019-4
Segel IH (1975) Enzyme kinetics : behavior and analysis of rapid equilibrium and steady state enzyme systems. Wiley. https://doi.org/10.2307/1297252
Shen YC, Wang T, Chen L, Yang T, Wan C, Hu QJ, Wen FQ (2013) Diagnostic accuracy of adenosine deaminase for tuberculous peritonitis: a meta-analysis. Arch Med Sci 9:601–607. https://doi.org/10.5114/aoms.2013.36904
Tamura K, Stecher G, Peterson D, Filipski A, Kumar S (2013) MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 30:2725–2729. https://doi.org/10.1093/molbev/mst197
Tellenbach C, Grunig CR, Sieber TN (2011) Negative effects on survival and performance of Norway spruce seedlings colonized by dark septate root endophytes are primarily isolate-dependent. Environ Microbiol 13:2508–2517. https://doi.org/10.1111/j.1462-2920.2011.02523.x
Tritsch GL (1983) Validity of the continuous spectrophotometric assay of Kalckar for adenosine deaminase activity. Anal Biochem1 29:207–209. https://doi.org/10.1016/0003-2697(83)90070-2
Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455–461. https://doi.org/10.1002/jcc.21334
Truyens S, Weyens N, Cuypers A, Vangronsveld J (2015) Bacterial seed endophytes: genera, vertical transmission and interaction with plants. Environ Microbiol Rep 7:40–50. https://doi.org/10.1111/1758-2229.12181
Uher M, Chalabala M, Cizmarik J (2000) [Kojic acid and its derivatives as potential therapeutic agents]. Ceska Slov Farm 49:288–298
Veverka M, Dubaj T, Gallovič J, Jorík V, Veverková E, Danihelová M, Šimon P (2015) Cocrystals of quercetin: synthesis, characterization, and screening of biological activity. Monatsh Chem Chem Mon 146:99–109. https://doi.org/10.1007/s00706-014-1314-6
Wang S-D, Ma Q, Wang K, Ma P-B (2018a) Strong and biocompatible three-dimensional porous silk fibroin/graphene oxide scaffold prepared by phase separation. Int J Biol Macromol 111:237–246. https://doi.org/10.1016/j.ijbiomac.2018.01.021
Wang G, Qiu J, Xiao X, Cao A, Zhou F (2018b) Synthesis, biological evaluation and molecular docking studies of a new series of chalcones containing naphthalene moiety as anticancer agents. Bioorg Chem 76:249–257. https://doi.org/10.1016/j.bioorg.2017.11.017
Wei J (1979) Fungal identification manual. Shang-hai Sci Technol Press
Wei S, Ji Z (2016) Isolation, synthesis, and antifungal activity of Kojic acid and its derivatives. Chem Nat Compd 52:1–2. https://doi.org/10.1007/s10600-016-1565-z
Yon C, Suh JW, Chang JH, Lim Y, Lee CH, Lee YS, Lee YW (1995) ChemInform abstract: AL072, a novel anti-legionella antibiotic produced by Streptomyces sp. J Antibiot 48:773–779. https://doi.org/10.1002/chin.199604270
Zhang XG, Peng YN, Li XR, Ma GD, Chen XQ (2015) Screening of iron-enriched fungus from natural environment and evaluation of organically bound iron bioavailability in rats. Food Sci Technol 35:58–65. https://doi.org/10.1590/1678-457X.6454
Zhang XG, Li XR, Wang QL, Wang WN, Chen XQ (2016) Study on effects of endophytes on growth and production of Z-Ligustilide and ferulic acid in Angelica sinensis. Braz J Bot 39:417–426. https://doi.org/10.1007/s40415-015-0245-8
Zhang XG, Liu JW, Tang P, Liu ZY, Guo GJ, Sun QY, Yin JJ (2017) Identification of a new uncompetitive inhibitor of adenosine deaminase from endophyte Aspergillus niger sp. Curr Microbiol 75:1–9. https://doi.org/10.1007/s00284-017-1418-4
Zhang Q, Song C, Zhao J, Shi X, Sun M, Liu J, Fu Y, Jin W, Zhu B (2018) Separation and characterization of Antioxidative and angiotensin converting enzyme inhibitory peptide from jellyfish gonad hydrolysate. Molecules 23:E94. https://doi.org/10.3390/molecules23010094
Funding
This research was supported by the program of National Natural Science Foundation of China under Grant (No. 31860004), Gansu province natural science fund (17JR5RA128), and the Fundamental Research Funds for Key Laboratory of Drug Screening and Deep Processing for Traditional Chinese and Tibetan Medicine of Gansu Province (No. 20180802).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Animal studies
This article does not contain any studies with animals performed by any of the authors.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Zhang, Xg., Sun, QY., Tang, P. et al. A new mixed inhibitor of adenosine deaminase produced by endophytic Cochliobolus sp. from medicinal plant seeds. Folia Microbiol 65, 293–302 (2020). https://doi.org/10.1007/s12223-019-00723-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12223-019-00723-1