Planta Med 2018; 84(11): 806-812
DOI: 10.1055/s-0043-124974
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Effective Antimalarial Activities of α-Hydroxy Diynes Isolated from Ongokea gore

Joséphine Kankolongo Ntumba
1   Department of Chemistry, Faculty of Sciences, University of Kinshasa, Democratic Republic of Congo
,
Christian Muamba Tshiongo
1   Department of Chemistry, Faculty of Sciences, University of Kinshasa, Democratic Republic of Congo
,
Michel Ngoma Mifundu
1   Department of Chemistry, Faculty of Sciences, University of Kinshasa, Democratic Republic of Congo
,
Raphäel Robiette
2   Institute of Condensed Matter and Nanosciences, Université Catholique de Louvain, Belgium
,
Kalulu Muzele Taba
1   Department of Chemistry, Faculty of Sciences, University of Kinshasa, Democratic Republic of Congo
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 03. Mai 2017
revised 28. November 2017

accepted 12. Dezember 2017

Publikationsdatum:
04. Januar 2018 (online)

Abstract

Three diynes, octadec-17-ene-9,11-diynoate ethyl (1), 8-hydroxy-octadeca-13,17-diene-9,11-diynoate ethyl (2), and 8-hydroxy-octadec-13-ene-9,11-diynoate ethyl (3), were isolated from Ongokea gore seed oil. The structure assignment of these three compounds was based according to chemical and spectroscopic data. They were screened against Plasmodium falciparum, the parasite that causes malaria. In vitro micro-test (Mark III, supported by the World Health Organization) was developed to assess the response of P. falciparum to the isolated three compounds, and statistical analysis were performed for determination of the concentration that inhibits 50% of the parasite maturation (IC50). Two of the three diynes (2 and 3) showed a very effective in vitro antimalarial activity with an IC50 of 4.5 and 1.7 µM, respectively. Compound 3 exhibited better activity than quinine (IC50 1.9 µM), the drug reference, while compound 1 had no antimalarial activity (IC50 > 125 µM). In the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxicity screening, all compounds showed no toxicity (mean IC50 of 90 µM for each compound).

Supporting Information

 
  • References

  • 1 WHO. A Global Brief on Vector-Borne Diseases. Geneva: World Health Organization; 2014
  • 2 Wallis RS, Maeurer M, Mwaba P, Chakaya J, Rustomjee R, Migliori GB, Marais B, Schito M, Churchyard G, Swaminathan S, Hoelscher M, Zumla A. Tuberculosis-advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers. Lancet Infect Dis 2016; 16: e34-e46
  • 3 WHO. World Malaria Report 2016. Geneva: World Health Organization; 2016
  • 4 Michal F, Duffy PE. Malaria during pregnancy. Cold Spring Harb Perspect Med 2017; 7: a025551
  • 5 Menéndez C, Ferenchick E, Roman E, Bardají A, Mangiaterra V. Malaria in pregnancy: challenges for control and the need for urgent action. Lancet Glob Health 2015; 3: e433-e434
  • 6 Ranson H, Lissenden N. Insecticide resistance in African anopheles mosquitoes: a worsening situation that needs urgent action to maintain malaria control. Trends Parasitol 2016; 32: 187-196
  • 7 Martin DJ, Isaacs AT, Weetman D. Identification, validation, and application of molecular diagnostics for insecticide resistance in malaria vectors. Trends Parasitol 2016; 32: 197-206
  • 8 Corey VC, Lukens AK, Istvan ES, Lee MC, Franco V, Magistrado P, Cobun-Flynn O, Sakata-Kato T, Fuchs O, Gnadig NF, Goldgof G, Linares M, Gomez-Lorenzo MG, De Cozar C, Lafuente-Monasterio MJ, Prats S, Meister S, Tanaseichuk O, Wree M, Zhou Y, Willis PA, Gamo FJ, Goldberg DE, Fidock DA, Wirth DF, Winzeler EA. A broad analysis of resistance development in the malaria parasite. Nat Commun 2016; 7: 11901
  • 9 Flannery EL, Chatterjee AK, Winzeler EA. Antimalarial drug discovery: approaches and progress towards new medicines. Nat Rev Microbiol 2013; 11: 849-862
  • 10 Kamaraj C, Rahuman AA, Roopan SM, Bagavan A, Elango G, Zahir AA, Rajakumar G, Jayaseelan C, Santhoshkumar T, Marimuthu S, Kirthi AV. Bioassay-guided isolation and characterization of active antiplasmodial compounds from Murraya koenigii extracts against Plasmodium falciparum and Plasmodium berghei . Parasitol Res 2014; 113: 1657-1672
  • 11 Chukwujekwu JC, de Kock CA, Smith PJ, Van Heerden FR, Van Staden J. Antiplasmodial activity of compounds isolated from Erythrina caffra . S Afr J Bot 2016; 106: 101-103
  • 12 Christensen LP, Brandt K. Bioactive polyacetylenes in food plants of the Apiaceae family occurrence, bioactivity and analysis. J Pharm Biomed Anal 2006; 41: 683-693
  • 13 Deng S, Wang Y, Inui T, Chen SN, Farnsworth NR, Cho S, Franzblau SG, Pauli GF. Anti-TB polyynes from the roots of Angelica sinesis . Phytother Res 2008; 22: 878-882
  • 14 Li XC, Jacob MR, Khan SI, Ashfaq KM, Babu KS, Agarwal AK, ElSohly HN, Manly SP, Clark AM. Potent in vitro antifungal activities of naturally occurring acetylenic acids. Antimicrob Agents Chemother 2008; 52: 2442-2448
  • 15 Zeni G, Panatieri RB, Lissner E, Menezes PH, Braga AL, Stefani HA. Synthesis of polyacetylenic acids isolated from Heisteria acuminate . Org Lett 2001; 3: 819-821
  • 16 Jia X, Yin K, Li C, Li J, Bian H. Copper-catalyzed oxidative alkyne homocoupling without palladium, ligands and bases. Green Chem 2011; 13: 2175-2178
  • 17 Mayer SF, Steinreiber A, Orru RV, Faber K. Chemoenzymatic asymmetric total syntheses of antitumor agents (3R,9R,10R)- and (3S,9R,10R)-Panaxytriol and (R)- and (S)-Falcarinol from Panax ginseng using an enantioconvergent enzyme-triggered cascade reaction. J Org Chem 2002; 67: 9115-9121
  • 18 Ohashi K, Winarno H, Mukai M, Inoue M, Prana MS, Simanjuntak P, Shibuya H. Cancer cell invasion inhibitory effects of chemical constituents in the parasitic plant Scurrula atropurpurea (Loranthaceae). Chem Pharm Bull 2003; 51: 343-345
  • 19 Senn M, Gunzenhauser S, Brun R, Séquin U. Antiprotozoal polyacetylenes from the Tanzanian medicinal plant Cussonia zimmermannii . J Nat Prod 2007; 70: 1565-1569
  • 20 Munirajasekhar D. Insecticidal activity of substituted 1,3-diynes. J Chem Pharm Res 2014; 6: 1204-1207
  • 21 Wang Y, Toyota M, Krause E, Hamburger M, Hostettman K. Polyacetylenes from Artemisza Borealis and their biological activities. Phytochem 1990; 10: 3101-3105
  • 22 Baxter PNM, Dali-Youcef R. Nitrogen heterocyclic carbon-rich materials: synthesis and spectroscopic properties of dehydropyridoannulene macrocycles. J Org Chem 2005; 70: 4935-4953
  • 23 Lam JWY, Tang BZ. Functional polyacetylenes. Acc Chem Res 2005; 38: 745-754
  • 24 Bandyopadhyay A, Varghese B, Sankararaman S. Synthesis of 1,4-cyclohexadiene-based acetylenic macrocycles with Cadiot-Chodkiewicz coupling. J Org Chem 2006; 71: 4544-4548
  • 25 Shi Shun ALK, Tykwinski RR. Synthesis of naturally occurring polyynes. Angew Chem Int Ed 2006; 45: 1034-1057
  • 26 Shi W. Conjugated diyne chemistry: synthesis, natural existence and applications. Curr Organocatal 2015; 2: 2-13
  • 27 Ntumba JK, Collard L, Taba KM, Robiette R. Isolation of a series of fatty acid components of Ongokea gore seed (isano) oil and their detailed structural analysis. Lipids 2015; 50: 313-322
  • 28 Miller RW, Weisleder D, Plattner RD, Smith CR. cis-Enediyne chromophore of isano oil. Lipids 1977; 12: 669-675
  • 29 World Health Organization. In Vitro Micro-Test (Mark III) for the Assessment of the Response of Plasmodium falciparum to Chloroquine, Mefloquine, Quinine, Amodiaquine, Sulfadoxine/Pyrimethamine and Artemisinin. CTD/MAL/97.20 Rev. 2, 2001. Available at. http://apps.who.int/iris/handle/10665/67373 Accessed December 22, 2017
  • 30 Balogun ST, Sandabe UK, Waziri IA, Jibrin J, Fehintola FA. In vitro sensitivity of Plasmodium falciparum clinical isolates to 4-aminoquinolines in northeast Nigeria. Malariaworld J 2016; 7: 10
  • 31 Bodeker GED, Willcox M. The first international meeting of the Research Initiative on Traditional Antimalarial Methods (RITAM). J Altern Complement Med 2000; 6: 195-207
  • 32 Hapuarachchi SV, Cobbold SA, Shafik SH, Dennis AM, McConville MJ, Martin RE, Kirk K, Lehane AM. The malaria parasiteʼs lactate transporter PfFNT is the target of antiplasmodial compounds identified in whole cell phenotypic screens. PLoS Pathog 2017; 13: e1006180
  • 33 Kirk K. Membrane transport in the malaria-infected erythrocyte. Physiol Rev 2001; 81: 495-537
  • 34 Fontanel D. Unsaponifiable Matter in Plant Seed Oils. Saint-Lézin, France: Springer; 2013: 2-11
  • 35 Mathieu V, Van Den Berge E, Ceusters J, Konopka T, Cops A, Bruyère C, Pirker C, Berger W, Trieu-Van T, Serteyn D, Kiss R, Robiette R. New 5-Aryl-1H-imidazoles display in vitro antitumor activity against apoptosis-resistant cancer models, including melanomas, through mitochondrial targeting. J Med Chem 2013; 56: 6626-6637
  • 36 Mijatovic T, Mathieu V, Gaussin JF, De Nève N, Ribaucour F, Van Quaquebeke E, Dumont P, Darro F, Kiss R. Cardenolide-induced lysosomal membrane permeabilization demonstrates therapeutic benefits in experimental human non-small cell lung cancers. Neoplasia 2006; 8: 402-412
  • 37 Christie WW. Preparation of Ester Derivatives of fatty Acids for chromatographic Analysis. In: Christie WW. ed. Advances in lipid Methodology, vol. 2. Dundee: Oily Press; 1993: 69-111
  • 38 Kuksis A. Lipids/Liquid chromatography. J Chromatogr 2000; 471: 204-219
  • 39 Saeed AEM, Bashier RSM. Physico-chemical analysis of Ximenia americana L. seed oil and structure elucidation of some chemical constituents of its seed oil and fruit pulp. J. Pharmacognosy Phytother 2010; 2: 49-55
  • 40 Stamenkovic OS, Velic AV, Veljkovic VB. The production of biodiesel from vegetable oils by ethanolysis: current state and perspectives. Fuel 2011; 90: 3141-3155
  • 41 Meneghetti SMP, Meneghetti MR, Wolf CR, Silva EC, Lima GES, Coimbra M, Soletti JI, Carvalho SHV. Ethanolysis of castor and cottonseed oil: a systematic study using classical catalysts. JAOCS 2006; 83: 819-821
  • 42 Kraus CM, Neszmelyi A, Sandor H, Wiedemann B, Nenninger A, Torssell KBG, Bohlin L, Wagner H. New acetylenes isolated from the bark of Heisteria acuminate . J Nat Prod 1998; 61: 422-427