Abstract
A series of naphthoquinone-benzothiazole conjugates were synthesized as algicides, and their efficacies against harmful algal blooming species, such as Chattonella marina, Heterosigma akashiwo and Cochlodinium polykrikoides, were examined. The introduction of substituted benzothiazole at the C2 position of 1,4-naphthoquinone (compounds 1–9) resulted in higher algicidal activity against C. polykrikoides than the C6 conjugates (compounds 10–20). On the other hand, of the C6 conjugates, compounds 11 and 12 exhibited better algicidal activity against H. akashiwo, C. marina, and C. polykrikoides than the C2 conjugates. Further structure-activity analysis indicated that a replacement of the methoxy groups with hydroxyl groups (compounds 21–26) decreased the algicidal activity significantly. Among the various synthetic naphthoquinonebezothiazole conjugates tested, compound 12 was found to affect the most significant decrease in the level of C. polykrikoides growth, with an IC50 of 0.19 μM. Compound 11 was found to be the most potent inhibitor against H. akashiwo and C. polykrikoides, with IC50 values of 0.32 and 0.12 μM, respectively. Overall, these results highlight a possible method for controlling and inhibiting red tide forming algae using NQ derivatives.
Similar content being viewed by others
References
Glibert, P. M., D. M. Anderson, P. Gentien, E. Graneli, and K. G. Sellner (2005) The global, complex phenomena of harmful algal blooms. Oceanography 18: 136–147.
Horner, R. A., D. L. Garrison, and F. G. Plumley (1997) Harmful algal blooms and red tide problems on the U. S. west coast. Limnol. Oceanogr. 42: 1076–1088.
Lee, M. O. and J. K. Kim (2008) Characteristics of algal blooms in the southern coastal waters of Korea. Mar. Environ. Res. 65: 128–147.
Stoecker, D. K., J. E. Adolf, A. R. Place, P. M. Glibert, and D. W. Meritt (2008) Effects of the dinoflagellates Karlodinium veneficum and Prorocentrum minimum on early life history stages of the eastern oyster (Crassostrea virginica). Mar. Biol. 154: 81–90.
Yoshinaga, I., T. Kawai, and Y. Ishida (1997) Analysis of algicidal ranges of the bacteria killing the marine dinoflagellate Gymnodinium mikimotoi isolated from Tanabe Bay, Wakayama Pref., Japan. Fish Sci. 63: 94–98.
Zingone, A. and H. O. Enevoldsen (2000) The diversity of harmful algal blooms: A challenge for science and management. Ocean Coast. Manag. 43: 725–748.
Landsberg, J. H. (2002) The effects of harmful algal blooms on aquatic organisms. Rev. Fish. Sci. 10: 113–390.
Sridhar, P., C. Namasivayam, and G. Prabhakaran (1988) Algae flocculation in reservoir water. Biotechnol. Bioeng. 32: 345–347.
Tenney, M. W., W. F. Echelberger, R. G. Schuessler, and J. L. Pavoni (1969) Algal flocculation with synthetic organic polyelectrolytes. Appl. Microbiol. 18: 965–971.
Sengco, M. R. and D. M. Anderson (2004) Controlling harmful algal blooms through clay flocculation. J. Eukaryot. Microbiol. 51: 169–172.
Shirota, A. (1989) Red tide problem and countermeasures (2). Int. J. Aquat. Fish. Technol. 1: 195–223.
Anderson, D. M. (1997) Turning back the harmful red tide. Nature 388: 513–514.
Sengco, M. R., A. Li, K. Tugend, D. Kulis, and D. M. Anderson (2001) Removal of red and brown tide cells using clay flocculation: I Laboratory culture experiments with Gymnodinum breve and Aureococcus anophagefferens. Mar. Ecol. Prog. Ser. 210: 41–53.
Kim, Y. M., Y. Wu, T. U. Duong, G. S. Ghodake, S. W. Kim, E. S. Jin, and H. Cho (2010) Thiazolidinediones as a novel class of algicides against red tide harmful algal species. Appl. Biochem. Biotechnol. 162: 2273–2283.
Kang, Y. H., J. D. Kim, B. H. Kim, D. S. Kong, and M. S. Han (2005) Isolation and characterization of a bio-agent antagonistic to diatom, Stephanodiscus hantzschii. J. Appl. Microbiol. 98: 1030–1038.
Su, J. Q., X. R. Yang, T. L. Zheng, Y. Tian, N. Z. Jiao, L. Z. Cai, and H. S. Hong (2007) Isolation and characterization of a marine algicidal bacterium against the toxic dinoflagellate Alexandrium tamarense. Harmful Algae 6: 799–810.
Wang, K. and F. Chen (2008) Prevalence of highly host-specific cyanophages in the estuarine environment. Environ. Microbiol. 10: 300–312.
Kim, Y. M., Y. Wu, T. U. Duong, S. G. Jung, S. W. Kim, H. Cho, and E. S. Jin (2012) Algicidal activity of thiazolidinedione derivatives against harmful algal blooming species. Mar. Biotechnol. 14: 312–322.
Tucker, C. S. (2000) Off-flavor problems in aquaculture. Rev. Fish. Sci. 8:45–88.
Schrader, K. K., N. P. Nanayakkara, C. S. Tucker, A. M. Rimando, M. Ganzera, and B. T. Schaneberg (2003) Novel derivatives of 9,10-anthraquinone are selective algicides against the musty-odor cyanobacterium Oscillatoria perornata. Appl. Environ. Microb. 69: 5319–5327.
Tewey, K. M., G. L. Chen, E. M. Nelson, and L. F. Liu (1984) Intercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II. J. Biol. Chem. 259: 9182–9187.
Leopold, W. R., J. L. Shillis, A. E. Mertus, J. M. Nelson, B. J. Roberts, and R. C. Jackson (1984) Anticancer activity of the structurally novel antibiotic Cl-920 and its analogues. Cancer Res. 44: 1928–1932.
Scheithauer, W., D. D. Von Hoff, G. M. Clark, J. L. Shillis, and E. F. Elslager (1986) In vitro activity of the novel antitumor antibiotic fostriecin (CI-920) in a human tumor cloning assay. Eur. J. Cancer Clin. Oncol. 22: 921–926.
Ting, C. Y., C. T. Hsu, J. S. Su, T. Y. Chen, W. Y. Tarn, Y. H. Kuo, J. Whang-Peng, L. F. Liu, and J. Hwang (2003) Isodiospyrin as a novel human DNA topoisomerase I inhibitor. Biochem. Pharmacol. 66: 1981–1991.
Chae, G. H., G. Y. Song, Y. Kim, H. Cho, E. E. Sok, and B. Z. Ahn (1999) 2- or 6-(1-Azidoalkyl)-5,8-dimethoxy-1,4-naphthoquinone: Synthesis, evaluation of cytotoxic activity, antitumor activity and inhibitory effect on DNA topoisomerase-I. Arch. Pharm. Res. 22: 507–514.
Song, G. Y., X. G. Zheng, Y. Kim, Y. J. You, D. E. Sok, and B. Z. Ahn (1999) Naphthazarin derivatives (II): Formation of glutathione conjugate, inhibition of DNA topoisomerase-I and cytotoxicity. Bioorg. Med. Chem. Lett. 9: 2407–2412.
Song, G. Y., Y. Kim, Y. J. You, H. Cho, S. H. Kim, D. E. Sok, and B. Z. Ahn (2000) Naphthazarin derivatives (VI): Synthesis, inhibitory effect on DNA topoisomerase-I and antiproliferative activity of 2- or 6-(1-oxyiminoalkyl)-5,8-dimethoxy-1,4-naphthoquinones. Arch. Pharm. Pharm. Med. Chem. 333: 87–92.
Song, G. Y., Y. Kim, X. G. Zheng, Y. J. You, H. Cho, J. H. Chung, D. E. Sok, and B. Z. Ahn (2000) Naphthazarin derivatives (IV): Synthesis, inhibition of DNA topoisomerase I and cytotoxicity of 2- or 6-acyl-5,8-dimethoxy-1, 4-naphthoquinones. Eur. J. Med. Chem. 35: 291–298.
Kim, Y., Y. J. You, and B. Z. Ahn (2001) Naphthazarin derivatives (VIII): Synthesis, inhibitory effect on DNA topoisomerase-I, and antiproliferative activity of 6-(1-acyloxyalkyl)-5,8-dimethoxy-1,4-naphthoquinones. Arch. Pharm. Pharm. Med. Chem. 334: 318–322.
Lown, J. W., S. K. Sim, K. C. Majumdar, and R. Y. Chang (1977) Strand scission of DNA by bound adriamycin and daunorubicin in the presence of reducing agents. Biochem. Biophys. Res. Commun. 76: 705–710.
Hertzberg, R. P. and P. B. Dervan (1984) Cleavage of DNA with methidiumpropyl-EDTA-iron(II): Reaction conditions and product analyses. Biochem. 23: 3934–3945.
Silverman, R. B. (1992) The Organic Chemistry of Drug Design and Drug Action. pp. 255–258. Academic Press, NY.
Inbaraj, J. J. and C. F. Chignell (2004) Cytotoxic action of juglone and plumbagin: A mechanistic study using HaCaT keratinocytes. Chem. Res. Toxicol. 17: 55–62.
Huang, S. T., H. S. Kuo, C. L. Hsiao, and Y. L. Lin (2002) Efficient synthesis of’ redox-switched’ naphthoquinone thiol-crown ethers and their biological activity evaluation. Bioorg. Med. Chem. 10: 1947–1952.
Tandon, V. K., R. B. Chhor, R. V. Singh, S. Rai, and D. B. Yadav (2004) Design, synthesis and evaluation of novel 1,4-naphthoquinone derivatives as antifungal and anticancer agents. Bioorg. Med. Chem. Lett. 14: 1079–1083.
Sasaki, K., H. Abe, and F. Yoshizaki (2002) In vitro antifungal activity of naphthoquinone derivatives. Biol. Pharm. Bull. 25: 669–670.
Lien, J. C., L. J. Huang, C. M. Teng, J. P. Wang, and S. C. Kuo (2002) Synthesis of 2-alkoxy 1,4-naphthoquinone derivatives as antiplatelet, antiinflammatory, and antiallergic agents. Chem. Pharm. Bull. 50: 672–674.
Jin, Y. R., C. K. Ryu, C. K. Moon, M. R. Cho, and Y. P. Yun (2004) Inhibitory effects of J78, a newly synthesized 1,4-naphthoquinone derivative, on experimental thrombosis and platelet aggregation. Pharmacol. 70: 195–200.
Kim, H. J., S. K. Kang, J. Y. Mun, Y. J. Chun, K. H. Choi, and M. Y. Kim (2003) Involvement of Akt in mitochondria-dependent apoptosis induced by a cdc25 phosphatase inhibitor naphthoquinone analog. FEBS Lett. 555: 217–222.
Richwien, A. and G. Wurm (2004) Influence of 2-aryl-3-halogen/3-hydroxy-1,4-naphthoquinones with salicylic and cinnamic acid partial structures on the arachidonic acid cascade. Pharmazie 59: 163–169.
Wurm, G. and S. Schwandt (2003) Methylated 2-aryl-1,4-naphtoquinone derivatives with diminished antioxidative activity. Pharmazie 58: 531–538.
Lanfranchi, D. A., E. Cesar-Rodo, B. Bertrand, H. H. Huang, L. Day, L. Johann, M. Elhabiri, K. Becker, D. L. Williams, and E. Davioud-Charvet (2012) Synthesis and biological evaluation of 1,4-naphthoquinones and quinoline-5,8-diones as antimalarial and schistosomicidal agents. Org. Biomol. Chem. 10: 6375–6387.
Sato, H., R. Yamada, M. Yanagihara, H. Okuzawa, H. Iwata, A. Kurosawa, S. Ichinomiya, R. Suzuki, H. Okabe, T. Yano, T. Kumamoto, N. Suzuki, T. Ishikawa, and K. Ueno (2012) New 2-aryl-1,4-naphthoquinone-1-oxime methyl ether compound induces microtubule depolymerization and subsequent apoptosis. J. Pharmacol. Sci. 118: 467–478.
Kuo, H. L., J. C. Lien, C. H. Chang, C. H. Chung, S. C. Kuo, C. C. Hsu, H. C. Peng, and T. F. Huang (2011) NP-313, 2-acetylamino-3-chloro-1,4-naphthoquinone, a novel antithrombotic agent with dual inhibition of thromboxane A(2) synthesis and calcium entry. Br. J. Pharmacol. 62: 1871–1883.
Havrylyuk, D., L. Mosula, B. Zimenkovsky, O. Vasylenko, A. Gzella, and R. Lesyk (2010) Synthesis and anticancer activity evaluation of 4-thiazolidinones containing benzothiazole moiety. Eur. J. Med. Chem. 45: 5012–5021.
Gilani, S. J., S. A. Khan, N. Siddiqui, S. P. Verma, P. Mullick, and O. Alam (2011) Synthesis and in vitro antimicrobial activity of novel N-(6-chlorobenzo[d]thiazol-2-yl) hydrazine carboxamide derivatives of benzothiazole class. J. Enz. Inhib. Med. Chem. 26: 332–340.
Jin, G. H., H. Li, S. An, J. H. Ryu, and R. Jeon (2010) Design, synthesis and activity of benzothiazole-based inhibitors of NO production in LPS-activated macrophages. Bioorg. Med. Chem. Lett. 20: 6199–6202.
Viegas-Junior, C., A. Danuello, V. da Silva Bolzani, E. J. Barreiro, and C. A. Fraga (2007) Molecular hybridization: a useful tool in the design of new drug prototypes. Cur. Med. Chem. 14: 1829–1852.
Chung, Y., Y. K. Shin, C. G. Zhan, S. Lee, and H. Cho (2004) Synthesis and evaluation of antitumor activity of 2- and 6-[(1,3-benzothiazol-2-yl)aminomethyl]-5,8-dimethoxy-1,4-naphthoquoinone derivatives. Arch. Pharm. Res. 27: 893–900.
Kim, B. H., J. Yoo, S. H. Park, J. K. Jung, Y. Chung, and H. Cho (2006) Synthesis and evaluation of antitumor activity of novel 1,4-naphthoquinone derivatives (IV). Arch. Pharm. Res. 29: 123–130.
Chung, Y., J. Yoo, S. H. Park, B. H. Kim, X. Chen, C. G. Zhan, and H. Cho (2007) Dependence of antitumor activity on the electrophilicity of 2-substituted 1,4-naphthoquinone derivatives. Bull. Kor. Chem. Soc. 28: 691–694.
Yoo, J., H. S. Choi, C. H. Choi, Y. Chung, B. H. Kim, and H. Cho (2008) Synthesis and evaluation of antitumor activity of novel 2-[N-methyl-N-(4-methyl-1,3-benzothiazol-2-yl)aminomethyl]-5,8-diacyloxy-1,4-naphthoquinones. Arch. Pharm. Res. 31: 142–147.
Benthey, W. H., R. Robinson, and C. Weizmann (1907) 3-Hydroxyphthalic and 3-methoxyphthalic acids and their derivatives. J. Chem. Soc. 91: 104–112.
Carter, A. H., E. Race, and F. M. Rowe (1942) Bromination of 1,5-dihydroxy- and 1,5-diacetoxynaphthalene, 5-methoxy-1-naphthol and 1,5-dimethoxynaphthalene. J. Chem. Soc. 236–239.
O’Brien, P. J. (1991) Molecular mechanisms of quinine cytotoxicity. Chem. Biol. Interact. 80: 1–41.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Kwon, H.L., Kim, JH., Na, D.H. et al. Combination of 1,4-naphthoquinone with benzothiazoles had selective algicidal effects against harmful algae. Biotechnol Bioproc E 18, 932–941 (2013). https://doi.org/10.1007/s12257-013-0284-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12257-013-0284-6