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: 05 nov. 2024.
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Articles