Bioguided-Fractionation of Butanolic Extract of Banjarmasin Soil Fungus Biomcc-F.T.3762 Fermentative Broth Against Plasmodium falciparum Dihydroorotate Dehydrogenase

  • AMILA PRAMISANDI BADAN PENGKAJIAN dan PENERAPAN TEKNOLOGI
  • HARMITA HARMITA UNIVERSITAS INDONESIA
  • ANIS HERLIYATI MAHSUNAH BADAN PENGKAJIAN dan PENERAPAN TEKNOLOGI

Abstract

Butanolic extract of soil fungus BioMCC-F.T.3762 fermentation broth exhibited inhibitory activity against Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH), a fl avin dependent mitochondrial electron transport chain, an essential enzyme in de novo pyrimidine biosynthesis pathway of the parasite. The crude butanolic extract exhibited PfDHODH inhibition of 97% at a concentration of 413 μg/mL, and showed no inhibitory activity against its human homolog. Bioassayguided fractionation was performed on butanolic extract of microbial fermentation broth to isolate the active compounds. The active fraction was isolated using liquid–liquid partition, silica gel column chromatography, octadecylsilane (ODS) column chromatography and was purifi ed by preparative high performance liquid chromatography (HPLC). Major peak of active fractions, FS10-2-12 and FS10-2- 13, were detected by PDA HPLC, which showed a retention time of 12.6 minute and 13.9 minute at 254 nm, respectively. The active fractions exhibited 75% and 40% inhibitory activity against PfDHODH, respectively, at a concentration of 100 μg/mL. In comparison, atpenin A5, a known potent mitochondrial complex II inhibitor exhibited 75% inhibitory activity againts PfDHODH at 366 μg/mL.

References

1. World Health Organization. 2015. World malaria report 2015. diambil dari: http://apps.who.int/iris/ bitstream/10665/200018/1/9789241565158_eng.pdf. diakses 4 Februari, 2016.

2. Kemenkes RI. 2013. Riset kesehatan dasar, Riskesdas 2013. diambil dari http://www.depkes.go.id/resources/ download/general/Hasil%20Riskesdas%202013.pdf. diakses 4 Februari, 2016.

3. RTS,S Clinical Trials Partnership et al. A phase 3 trial of RTS,S/AS01 malaria vaccine in African Infants. N Engl J Med. 2012. 367:2284-95.

4. Rodrigues T, Lopes F, & Moreira R. Inhibitors of the mitochondrial electron transport chain and the novo pyrimidine biosynthesis as antimalarials: the present status. Curr Med Chem. 2010.17:929-56.

5. Nixon GL, Pidathala C, Shone AE, Antoine T, Fisher N, O’neill PM et al. Targeting the mitochondrial electron transport chain of Plasmodium falciparum: new strategies towards the development of improved antimalarials for the elimination era. Future Med Chem. 2013.5(13):1573-91.

6. Baumgartner R, Walloschek M, Kralik M, Gotschlich A, Tasler S, Mies J, et al. Dual binding mode of a novel series of DHODH inhibitors. J Med Chem. 2006.49:1239-47.

7. Phillips MA, White KL, Kokkonda S, Deng X, White J, Mazouni FE, et al. Triazolopyrimidine-based dihydroorotate dehydrogenase inhibitors with potent and selective activity against the malaria parasite Plasmodium falciparum. J Med Chem. 2008.51:3649- 53.

8. Deng X, Gujjar R, El Mazouni F, Kaminsky W, Malmquist NA, Goldsmith EJ, et al. Structural plasticity of malaria dihydroorotate dehydrogenase allows selective binding of diverse chemical scaff olds. J Biol Chem. 2009.284:26999-27009.

9. Stocks PA, Barton V, Antoine T, Biagini GA, Ward SA, & O’neill PM. Novel inhibitors of the Plasmodium falciparum electron transport chain. J Parasitol. 2014.141:50-65.

10. Demain AL & Sanchez S. Microbial drug discovery: 80 years of progress. J Antibiot. 2009.62:5-16.

11. Otoguro K, Ui H, Ishiyama A, Arai N, Kobayashi M, Takahashi Y, et al. In vitro antimalarial activities of the microbial metabolites. J Antibiot. 2003.56(3):322-4. 12. Sunaryanto R & Mahsunah AH. Isolation, purifi cation, and characterization of antimicrobial substances from endophytic actinomycetes. Makara J Sci. 2013.17(3):87-92.

13. Kita K, Shiomi K & Ōmura S. Advances in drug discovery and biochemical studies. Trends in Parasitology. 2007.23(5):223-9.
Published
2017-04-30
How to Cite
PRAMISANDI, AMILA; HARMITA, HARMITA; MAHSUNAH, ANIS HERLIYATI. Bioguided-Fractionation of Butanolic Extract of Banjarmasin Soil Fungus Biomcc-F.T.3762 Fermentative Broth Against Plasmodium falciparum Dihydroorotate Dehydrogenase. JURNAL ILMU KEFARMASIAN INDONESIA, [S.l.], v. 15, n. 1, p. 1-6, apr. 2017. ISSN 2614-6495. Available at: <http://jifi.farmasi.univpancasila.ac.id/index.php/jifi/article/view/445>. Date accessed: 24 nov. 2024.
Citation Formats
Issue
Vol 15 No 1 (2017): JIFI
Section
Articles
License

Licencing
All articles in Jurnal Ilmu Kefarmasian Indonesia are an open-access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which permits unrestricted non-commercial used, distribution and reproduction in any medium.

This licence applies to Author(s) and Public Reader means that the users mays :

  • SHARE:
    copy and redistribute the article in any medium or format
  • ADAPT:
    remix, transform, and build upon the article (eg.: to produce a new research work and, possibly, a new publication)
  • ALIKE:
    If you remix, transform, or build upon the article, you must distribute your contributions under the same license as the original.
  • NO ADDITIONAL RESTRICTIONS:
    You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.

It does however mean that when you use it you must:

  • ATTRIBUTION: You must give appropriate credit to both the Author(s) and the journal, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.

You may not:

  • NONCOMMERCIAL: You may not use the article for commercial purposes.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.