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Isolation of Candida albicans Chitin Synthase 1 Inhibitor from Streptomyces sp. A6705 and Its Characterization

KIM NA RAE    (Laboratory of Cellular Function Modulator, Korea Research Institute of Bioscience and Biotechnology   ); HWANG EUI IL    (Bio Research Group, KT&G Central Research Institute   ); YUN BONG SIK    (Laboratory of Cellular Function Modulator, Korea Research Institute of Bioscience and Biotechnology   ); LEE SANG HAN    (Laboratory of Cellular Function Modulator, Korea Research Institute of Bioscience and Biotechnology   ); MOON JAE SUN    (Laboratory of Cellular Function Modulator, Korea Research Institute of Bioscience and Biotechnology   ); LIM CHI HWAN    (Department of Agricultural Chemistry, Graduate School, Chungnam National University   ); LIM SE JIN    (College of Pharmacy, Dongduk Women's University   ); KIM SUNG UK    (Laboratory of Cellular Function Modulator, Korea Research Institute of Bioscience and Biotechnology  );
  • 초록

    In the course of searching for potent chitin synthase 1 inhibitors from natural resources, Streptomyces sp. A6705 was found to exhibit potent inhibitory activity against the chitin synthase 1 from C. albicans (CaCHS1p). As a result, the inhibitor was isolated and identified using a series of chromatographies. Through chemical analyses with UV spectrophotometry, MS spectrometry, and various NMR techniques, the inhibitor was identified as N,N-bis(2-phenylethyl)urea. The compound exhibited strong inhibitory activity against the chitin synthase 1 from C. albicans with an $IC_{50}$ of 14 ${\mu}g$ /ml, representing a similar inhibitory activity to that of the well-known chitin synthase inhibitor, polyoxin D ( $IC_{50}$ 15 ${\mu}g$ /ml). However, the compound showed no inhibitory activity against the chitin synthase 2 of Saccharomyces cerevisiae up to 280 ${\mu}g$ /ml, which is structurally and functionally analogous to CaCHS 1 p. In addition, the compound exhibited weak antifungal activities against Cryptococcus neoformans and Rhizoctonis solani.


  • 주제어

    Candida albicans .   chitin synthase 1 inhibitor .   chemotaxonomy .   N,N-bis(2-phenylethyl)urea.  

  • 참고문헌 (18)

    1. Sudoh, M., T. Yamazaki, K. Masubuchi, M. Taniguchi, N. Shimma, M. Arisawa, and H. Yamada-Okabe. 2000. Identification of a novel inhibitor specific to the fungal chitin synthase. J. Biol. Chem. 275: 32901-32905 
    2. Jiang, B., H. Bussey, and T. Roemer. 2002. Novel strategies in antifungal lead discovery. Curr. Opin. Microbiol. 5: 466-471 
    3. Au-Young, J. and P. W. Robbins. 1990. Isolation of a chitin synthetase gene (CHSl) from Candida albicans by expression in Saccharomyces cerevisiae. Mol. Microbiol. 4: 197-207 
    4. Munro. C. A. and N. A. R. Gow. 1995. Chitin biosynthesis as a target for antifungals, pp. 161- 171. In G K. Dixon, L. G Copping, and D. W. Hollomon (eds.), Antifungal Agents: Discovery and Mode of Action. Bios Scientific Publisher, Oxford, U.K 
    5. Choi, W. J. 1998. The determination of chitin synthases by varying pH and divalent cations in Candida albicans. J. Microbiol. Biotechnol. 8: 613-617 
    6. Bulawa, C. E. 1993. Genetics and molecular biology of chitin synthesis in fungi. Annu. Rev. Microbiol. 47: 505-534 
    7. Mcginnis, M. R. and M. G Rinaldi. 1986. Antifungal drugs: Mechanisms of action, drug resistance, susceptibility testing, and assays of activity in biological fluids, pp. 223-281. In L. Victor (ed.), Antibiotics in Laboratory Medicine, 2nd ed. Williams and Wilkins, Baltimore, U.S.A 
    8. Park, K. S., K. C. Kang, K. Y. Kim, P. Y. Jeong, J. H. Kim, D. J. Adams, J. H. Kim, and Y. K. Paik. 2001. HWY-289, a novel semi-synthetic protoberberine derivative with multiple target sites in Candida albicans. J. Antimicrob. Chemother. 47: 513-519 
    9. Hwang, E. J., B. M. Kwon, S. H. Lee, N. R. Kim, J. H. Kang, Y. T. Kim, B. K. Park, and S. U. Kim. 2002. Obovatols, new chitin synthase 2 inhibitors of Saccharomyces cerevisiae from Magnolia obovata. J. Antimicrob. Chemother. 49: 95-101 
    10. Locci, R. 1989. Streptomycetes and related genera, pp. 2451-2492. In S. J. Williams, M. E. Sharpe, and J. G. Holt (eds.), Bergey's Manual of Systematic Bacteriology, Vol. 4. Williams and Wilkins, Baltimore, U.S.A 
    11. Park, K. S., K. C. Kang, J. H. Kim, D. J. Adams, J. N. Johng, and Y. K. Paik. 1999. Differential inhibitory effects of protoberberines on sterol and chitin biosyntheses in Candida albicans. J. Antimicrob. Chemother. 43: 667-674 
    12. Orlean, P. 1987. Two chitin synthases in Saccharomyces cerevisiae. J. Biol. Chem. 262: 5732-5739 
    13. Sudoh, M., K. Tatsuno, N. Ono, A. Ohta, H. Chibana, H. Yamada-Okabe, and M. Arisawa. 1999. The Candida albicans CHS4 gene complements a Saccharomyces cerevisiae Skt5/ chs4 mutation and is involved in chitin biosynthesis. Microbiology 145: 1613-1622 
    14. Mio, T., T. Yabe, M. Sudoh, Y. Satoh, T. Nakajima, M. Arisawa, and H. Yamada-Okada. 1996. Role of three chitin synthase genes in the growth of Candida albicans. J. Bacteriol. 178: 2416-2419 
    15. Daoud, N. N. and H. A. Foster. 1993. Antifungal activity of Myxococcus species. I Production, physicochemical and biological properties of antibiotics from Myxococcus fitlvus S 110 (Myxobacterales). Microbios 73: 173-18 
    16. Chiou, C. C., A. H. Groll, and T. J. Walsh. 2000. New drugs and novel targets for treatment of invasive fungal infections in patients with cancer. Oncologist 5: 120-135 
    17. Iwai, Y., A. Hirano, J. Awaya, S. Matsuo, and S. Omura. 1978. 1,3-Diphenethylurea from Streptomyces sp. No. AM2498. J. Antibiot. 31: 375-376 
    18. Munro, C. A., K. Winter, A. Buchan, and N. A. R. Gow. 2001. Chs 1 of Candida albicans is an essential chitin synthase required for synthesis of the septum and for cell integrity. Mol. Microbiol. 39: 1414-1426 

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