DOI QR코드

DOI QR Code

Thiolactomide: A New Homocysteine Thiolactone Derivative from Streptomyces sp. with Neuroprotective Activity

  • Jang, Jun-Pil (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kwon, Min Cheol (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Nogawa, Toshihiko (RIKEN Center for Sustainable Research Science) ;
  • Takahashi, Shunji (Natural Products Biosynthesis Research Unit and RIKEN-KRIBB Joint Research Unit, RIKEN Center for Sustainable Research Science) ;
  • Osada, Hiroyuki (RIKEN Center for Sustainable Research Science) ;
  • Ahn, Jong Seog (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Ko, Sung-Kyun (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jang, Jae-Hyuk (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2021.08.16
  • Accepted : 2021.09.13
  • Published : 2021.12.28

Abstract

A new homocysteine thiolactone derivative, thiolactomide (1), was isolated along with a known compound, N-acetyl homocysteine thiolactone (2), from a culture extract of soil-derived Streptomyces sp. RK88-1441. The structures of these compounds were elucidated by detailed NMR and MS spectroscopic analyses with literature study. In addition, biological evaluation studies revealed that compounds 1 and 2 both exert neuroprotective activity against 6-hydroxydopamine (6-OHDA)-mediated neurotoxicity by blocking the generation of hydrogen peroxide in neuroblastoma SH-SY5Y cells.

Keywords

Acknowledgement

We would like to thank Dr. T Nakamura at RIKEN for the HRESIMS measurements. This work was supported by the National Research Foundation of Korea (NRF) (Grant No. NRF-2021M3H9A1037439) and the KRIBB Research Initiative Program (KGM5292113 and JHM0022111) funded by the Ministry of Science ICT (MSIT) of the Republic of Korea. We thank the Korea Basic Science Institute, Ochang, Korea, for providing the NMR (700 and 800MHz) and HR-ESI-MS.

References

  1. Newman DJ, Cragg GM. 2020. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J. Nat. Prod. 83: 770-803. https://doi.org/10.1021/acs.jnatprod.9b01285
  2. Butler MS, Robertson AA, Cooper MA. 2014. Natural product and natural product derived drugs in clinical trials. Nat. Prod. Rep. 31: 1612-1661. https://doi.org/10.1039/C4NP00064A
  3. Berdy J. 2005. Bioactive microbial metabolites. J. Antibiot. 58: 1-26. https://doi.org/10.1038/ja.2005.1
  4. Genilloud O, Gonzalez I, Salazar O, Martin J, Tormo JR, Vicente F. 2011. Current approaches to exploit actinomycetes as a source of novel natural products. J. Ind. Microbiol. Biotechnol. 38: 375-389. https://doi.org/10.1007/s10295-010-0882-7
  5. Osada H. 2000. in Bioprobes, pp. 1-14. Ed. Springer, Berlin.
  6. Osada H. 2009. Chemical biology based on small molecule-protein interaction, pp. 1-10. Ed. Wiley, New Jersey.
  7. Jang JP, Takahashi S, Futamura Y, Nogawa T, Jang JH, Ahn JS, et al. 2017. RK-144171, a new benadrostin derivative produced by Streptomyces sp. RK88-1441. J. Antibiot. 70: 102-104. https://doi.org/10.1038/ja.2016.65
  8. Osada H, Ishinabe K, Yano T, Kajikawa K, Isono K. 1990. New pyrrolobenzodiazepine antibiotics, RK-1441A and B. I. Biological properties. Agric. Biol. Chem. 54: 2875-2881. https://doi.org/10.1271/bbb1961.54.2875
  9. Jizba JV, Sedmera P, Vanek Z, Drautz H, Zahner H. 1985. Two thiolactones from Streptomyces Tu 2476. J. Antibiot. 38: 111-112. https://doi.org/10.7164/antibiotics.38.111
  10. Meguro H, Konno T, Tuzimura K.1972. Circular dichroism of thiolo-g-lactones and their configurations and conformations. Tetrahedron Lett. 31: 3165-3168. https://doi.org/10.1016/S0040-4039(01)93993-0
  11. Kamat PK, Kalani A, Rai S, Swarnkar S, Tota S, Nath C, et al. 2016. Mechanism of oxidative stress and synapse dysfunction in the pathogenesis of Alzheimer's disease: understanding the therapeutics strategies. Mol. Neurobiol. 53: 648-661. https://doi.org/10.1007/s12035-014-9053-6
  12. Beyrent E, Gomez G. 2020. Oxidative stress differentially induces tau dissociation from neuronal microtubules in neurites of neurons cultured from different regions of the embryonic Gallus domesticus brain. J. Neurosci. Res. 98: 734-747. https://doi.org/10.1002/jnr.24541
  13. Zhao H, Han Z, Ji X, Luo Y. 2016. Epigenetic regulation of oxidative stress in ischemic stroke. Aging Dis. 7: 295-306. https://doi.org/10.14336/ad.2015.1009
  14. Dias V, Junn E, Mouradian MM. 2013. The role of oxidative stress in Parkinson's disease. J. Parkinsons Dis. 3: 461-491. https://doi.org/10.3233/JPD-130230
  15. Simola N, Morelli M, Carta AR. 2007. The 6-hydroxydopamine model of Parkinson's disease. Neurotox. Res. 11: 151-167. https://doi.org/10.1007/BF03033565
  16. Jagmag SA, Tripathi N, Shukla SD, Maiti S, Khurana S. 2015. Evaluation of models of Parkinson's disease. Front. Neurosci. 9: 503. https://doi.org/10.3389/fnins.2015.00503
  17. Leanza WJ, Chupak LS, Tolman RL, Marburg S. 1992. Acidic derivatives of homocysteine thiolactone: utility as anionic linkers. Bioconjug. Chem. 3: 514-518. https://doi.org/10.1021/bc00018a009
  18. McCully KS, Vezeridis MP. 1988. Homocysteine thiolactone in arteriosclerosis and cancer. Res. Commun. Chem. Pathol. Pharmacol. 59: 107-119.
  19. de Barrio M, Tornero P, Prieto A, Sainza T, Zubeldia JM, Herrero T. 1997. Recurrent fixed drug eruption caused by citiolone. J. Investig. Allergol. Clin. Immunol. 7: 193-194.
  20. Miglio F, D'Ambro A, Stefanini GF, Corazza GR, Pesa O, Flacco L, et al. 1977. Use of citiolone in chronic hepatitides. Results of a research with clinical and laboratory controls. Minerva Med. 68: 3177-3192.