Advanced search
Publication Cover
Expert Opinion on Therapeutic Patents Volume 26, 2016 - Issue 1
Submit an article Journal homepage
301
Views
8
CrossRef citations to date
0
Altmetric
Reviews

Antiplasmodial drug targets: a patent review (2000 – 2013)

John OkomboDepartment of Chemistry, University of Cape Town, Rondebosch 7701, South Africa;South African Medical Research Council Drug Discovery and Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa
&
Kelly ChibaleDepartment of Chemistry, University of Cape Town, Rondebosch 7701, South Africa;South African Medical Research Council Drug Discovery and Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa;Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South AfricaCorrespondence[email protected]
Pages 107-130 | Published online: 13 Nov 2015

Bibliography

••First report to document the emergence of artemisinin-resistant Plasmodium falciparum parasite strains in south East Asia.

••First article to publish the complete genome of Plasmodium falciparum describing the orientation of genes through 14 chromosomes and annotating function to some of the genes.

••Excellent review describing various peptides with antimalarial properties, their potential modes of action and the merits of exploring them as antimalarial drug candidates.

  • Fong KY, Wright DW. Hemozoin and antimalarial drug discovery. Future Med Chem. 2013;5:1437–1450.
  • Sullivan DJ. Plasmodium drug targets outside the genetic control of the parasite. Curr Pharm Des. 2013;19:282–289.
  • Leed A, DuBay K, Ursos LM, et al. Solution structures of antimalarial drug-heme complexes. Biochemistry. 2002;41:10245–10255.
  • Sullivan DJ Jr, Gluzman IY, Goldberg DE. Plasmodium hemozoin formation mediated by histidine-rich proteins. Science. 1996;271:219–222.
  • Kannan R, Sahal D, Chauhan VS. Heme-artemisinin adducts are crucial mediators of the ability of artemisinin to inhibit heme polymerization. Chem Biol. 2002;9:321–332.
  • Bendrat K, Berger BJ, Cerami A. Haem polymerization in malaria. Nature. 1995;378:138–139.
  • Fitch CD, Cai GZ, Chen YF, et al. Involvement of lipids in ferriprotoporphyrin IX polymerization in malaria. Biochim Biophys Acta. 1999;1454:31–37.
  • Rathore D, Jani D, Nagarkatti R. Novel therapeutic target for protozoal diseases. US20070148185Al. 2007.
  • Niles JC, Derisi JL, Marletta MA. Inhibiting Plasmodium falciparum growth and heme detoxification pathway using heme-binding DNA aptamers. Proc Natl Acad Sci USA. 2009;106:13266–13271.
  • Yoshida M, Horinouchi S, Beppu T. Trichostatin A and trapoxin: novel chemical probes for the role of histone acetylation in chromatin structure and function. Bioessays. 1995;17:423–430.
  • Sanchez del Pino MM, Lopez-Rodas G, Sendra R, et al. Properties of the yeast nuclear histone deacetylase. Biochem J. 1994;303(Pt 3):723–729.
  • Furumai R, Komatsu Y, Nishino N, et al. Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin. Proc Natl Acad Sci USA. 2001;98:87–92.
  • Singh SB, Zink DL, Liesch JM, et al. Structure and chemistry of apicidins, a class of novel cyclic tetrapeptides without a terminal alpha-keto epoxide as inhibitors of histone deacetylase with potent antiprotozoal activities. J Org Chem. 2002;67:815–825.
  • Dulski P, Myers R, Gumett A, et al. Histone deacetylase as target for antiprotozoal agents. US6428983B1. 2002.
  • Elbadawi MA, Awadalla MK, Hamid MM, et al. Valproic acid as a potential inhibitor of Plasmodium falciparum histone deacetylase 1 (PfHDAC1): an in silico approach. Int J Mol Sci. 2015;16:3915–3931.
  • Giannini G, Battistuzzi G, Vignola D. Hydroxamic acid based histone deacetylase inhibitors with confirmed activity against the malaria parasite. Bioorg Med Chem Lett. 2015;25:459–461.
  • Dow GS, Chen Y, Andrews KT, et al. Antimalarial activity of phenylthiazolyl-bearing hydroxamate-based histone deacetylase inhibitors. Antimicrob Agents Chemother. 2008;52:3467–3477.
  • Sumanadasa SD, Goodman CD, Lucke AJ, et al. Antimalarial activity of the anticancer histone deacetylase inhibitor SB939. Antimicrob Agents Chemother. 2012;56:3849–3856.
  • Hansen FK, Sumanadasa SD, Stenzel K, et al. Discovery of HDAC inhibitors with potent activity against multiple malaria parasite life cycle stages. Eur J Med Chem. 2014;82:204–213.
  • Patel V, Mazitschek R, Coleman B, et al. Identification and characterization of small molecule inhibitors of a class I histone deacetylase from Plasmodium falciparum. J Med Chem. 2009;52:2185–2187.
  • Sriwilaijaroen N, Boonma S, Attasart P, et al. Inhibition of Plasmodium falciparum proliferation in vitro by double-stranded RNA directed against malaria histone deacetylase. Biochem Biophys Res Commun. 2009;381:144–147.
  • Baum J, Papenfuss AT, Mair GR, et al. Molecular genetics and comparative genomics reveal RNAi is not functional in malaria parasites. Nucleic Acids Res. 2009;37:3788–3798.
  • Mueller AK, Hammerschmidt-Kamper C, Kaiser A. RNAi in Plasmodium. Curr Pharm Des. 2014;20:278–283.
  • Mao X, Schwer B, Shuman S. Mutational analysis of the Saccharomyces cerevisiae ABD1 gene: cap methyltransferase activity is essential for cell growth. Mol Cell Biol. 1996;16:475–480.
  • Wang SP, Shuman S. Structure-function analysis of the mRNA cap methyltransferase of Saccharomyces cerevisiae. J Biol Chem. 1997;272:14683–14689.
  • Schwer B, Mao X, Shuman S. Accelerated mRNA decay in conditional mutants of yeast mRNA capping enzyme. Nucleic Acids Res. 1998;26:2050–2057.
  • Lampio A, Ahola T, Darzynkiewicz E, et al. Guanosine nucleotide analogs as inhibitors of alphavirus mRNA capping enzyme. Antiviral Res. 1999;42:35–46.
  • Chrebet GL, Wisniewski D, Perkins AL, et al. Cell-based assays to detect inhibitors of fungal mRNA capping enzymes and characterization of sinefungin as a cap methyltransferase inhibitor. J Biomol Screen. 2005;10:355–364.
  • Shuman S, Ho CK. Pharmacological targeting of mRNA cap formation for treatment of parasitic infections. US20030166209A1. 2003.
  • Messika E, Golenser J, Abu-Elheiga L, et al. Effect of sinefungin on macromolecular biosynthesis and cell cycle of Plasmodium falciparum. Trop Med Parasitol. 1990;41:273–278.
  • Trager W, Tershakovec M, Chiang PK, et al. Plasmodium falciparum: antimalarial activity in culture of sinefungin and other methylation inhibitors. Exp Parasitol. 1980;50:83–89.
  • Dobeli H, Trzeciak A, Gillessen D, et al. Expression, purification, biochemical characterization and inhibition of recombinant Plasmodium falciparum aldolase. Mol Biochem Parasitol. 1990;41:259–268.
  • Dobeli H, Itin C, Meier B, et al. Is Plasmodium falciparum aldolase useful for rational drug design? Acta Leiden. 1991;60:135–140.
  • Viswanath NVN, Kodam J. Genes and protein sequences useful as drug targets for therapeutic action against protozoa. US20040082048A1. 2004.
  • Menting JG, Tilley L, Deady LW, et al. The antimalarial drug, chloroquine, interacts with lactate dehydrogenase from Plasmodium falciparum. Mol Biochem Parasitol. 1997;88:215–224.
  • Read JA, Wilkinson KW, Tranter R, et al. Chloroquine binds in the cofactor binding site of Plasmodium falciparum lactate dehydrogenase. J Biol Chem. 1999;274:10213–10218.
  • Penna-Coutinho J, Cortopassi WA, Oliveira AA, et al. Antimalarial activity of potential inhibitors of Plasmodium falciparum lactate dehydrogenase enzyme selected by docking studies. PLoS One. 2011;6:e21237.
  • Choi SR, Pradhan A, Hammond NL, et al. Design, synthesis, and biological evaluation of Plasmodium falciparum lactate dehydrogenase inhibitors. J Med Chem. 2007;50:3841–3850.
  • Shahabuddin M, Toyoshima T, Aikawa M, et al. Transmission-blocking activity of a chitinase inhibitor and activation of malarial parasite chitinase by mosquito protease. Proc Natl Acad Sci USA. 1993;90:4266–4270.
  • Flores MV, Atkins D, Wade D, et al. Inhibition of Plasmodium falciparum proliferation in vitro by ribozymes. J Biol Chem. 1997;272:16940–16945.
  • Hoen R, Novoa EM, Lopez A, et al. Selective inhibition of an apicoplastic aminoacyl-tRNA synthetase from Plasmodium falciparum. Chembiochem. 2013;14:499–509.
  • Makanga M, Bray PG, Horrocks P, et al. Towards a proteomic definition of CoArtem action in Plasmodium falciparum malaria. Proteomics. 2005;5:1849–1858.
  • Radfar A, Diez A, Bautista JM. Chloroquine mediates specific proteome oxidative damage across the erythrocytic cycle of resistant Plasmodium falciparum. Free Radic Biol Med. 2008;44:2034–2042.
  • Briolant S, Almeras L, Belghazi M, et al. Plasmodium falciparum proteome changes in response to doxycycline treatment. Malar J. 2010;9:141.
  • Deng W, Baker DA. A novel cyclic GMP-dependent protein kinase is expressed in the ring stage of the Plasmodium falciparum life cycle. Mol Microbiol. 2002;44:1141–1151.
  • Gurnett AM, Liberator PA, Dulski PM, et al. Purification and molecular characterization of cGMP-dependent protein kinase from Apicomplexan parasites. A novel chemotherapeutic target. J Biol Chem. 2002;277:15913–15922.
  • Donald RG, Allocco J, Singh SB, et al. Toxoplasma gondii cyclic GMP-dependent kinase: chemotherapeutic targeting of an essential parasite protein kinase. Eukaryot Cell. 2002;1:317–328.
  • Nare B, Allocco JJ, Liberator PA, et al. Evaluation of a cyclic GMP-dependent protein kinase inhibitor in treatment of murine toxoplasmosis: gamma interferon is required for efficacy. Antimicrob Agents Chemother. 2002;46:300–307.
  • Wiersma HI, Galuska SE, Tomley FM, et al. A role for coccidian cGMP-dependent protein kinase in motility and invasion. Int J Parasitol. 2004;34:369–380.
  • Liberator P, Schmatz D, Gurnett A, et al. DNA encoding novel cyclic GMP dependent protein kinases from two protozoal sources for use as chemotherapeutic tagets for antiprotozoal agents. US20050147628A1. 2005.
  • Taylor HM, McRobert L, Grainger M, et al. The malaria parasite cyclic GMP-dependent protein kinase plays a central role in blood-stage schizogony. Eukaryot Cell. 2010;9:37–45.
  • Kumar R, Adams B, Oldenburg A, et al. Characterisation and expression of a PP1 serine/threonine protein phosphatase (PfPP1) from the malaria parasite, Plasmodium falciparum: demonstration of its essential role using RNA interference. Malar J. 2002;1:5.
  • Lindenthal C, Klinkert MQ. Identification and biochemical characterisation of a protein phosphatase 5 homologue from Plasmodium falciparum. Mol Biochem Parasitol. 2002;120:257–268.
  • Adams JH, Balu B, Maher SP, et al. Method and composition using a dual specificity protein tyrosine phosphatase as an antimalarial drug target. US20120077869A1. 2012.
  • Campbell CO, Santiago DN, Guida WC, et al. In silico characterization of an atypical MAPK phosphatase of Plasmodium falciparum as a suitable target for drug discovery. Chem Biol Drug Des. 2014;84:158–168.

•This article combines computational modeling and in vitro analysis to identify and validate mitogen-activated protein kinase as new class of Plasmodium falciparum drug target.

  • Marrakchi H, Ducasse S, Labesse G, et al. MabA (FabG1), a Mycobacterium tuberculosis protein involved in the long-chain fatty acid elongation system FAS-II. Microbiology. 2002;148:951–960.
  • Surolia N, Surolia A. Triclosan offers protection against blood stages of malaria by inhibiting enoyl-ACP reductase of Plasmodium falciparum. Nat Med. 2001;7:167–173.
  • Rock CO, Cronan JE. Escherichia coli as a model for the regulation of dissociable (type II) fatty acid biosynthesis. Biochim Biophys Acta. 1996;1302:1–16.
  • Bergler H, Wallner P, Ebeling A, et al. Protein EnvM is the NADH-dependent enoyl-ACP reductase (FabI) of Escherichia coli. J Biol Chem. 1994;269:5493–5496.
  • Turnowsky F, Fuchs K, Jeschek C, et al. envM genes of Salmonella typhimurium and Escherichia coli. J Bacteriol. 1989;171:6555–6565.
  • Ramya TN, Surolia N, Surolia A. Is the fatty acid synthesis pathway a good target for anti-malarial therapy? IUBMB Life. 2005;57:371–373.
  • Surolia N, RamachandraRao SP, Surolia A. Paradigm shifts in malaria parasite biochemistry and anti-malarial chemotherapy. Bioessays. 2002;24:192–196.
  • Vaughan AM, O’Neill MT, Tarun AS, et al. Type II fatty acid synthesis is essential only for malaria parasite late liver stage development. Cell Microbiol. 2009;11:506–520.
  • Yeh E, DeRisi JL. Chemical rescue of malaria parasites lacking an apicoplast defines organelle function in blood-stage Plasmodium falciparum. PLoS Biol. 2011;9:e1001138.
  • Surolia A, Sharma SK, Kapoor M, et al. FabZ as a target for treating human malaria and other infections diseases with NAS-91 and NAS-21 as antimicrobial and antimalarial agents. IN 2003CH00554A. 2005.
  • Sharma SK, Kapoor M, Ramya TN, et al. Identification, characterization, and inhibition of Plasmodium falciparum beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ). J Biol Chem. 2003;278:45661–45671.
  • Kostrewa D, Winkler FK, Folkers G, et al. The crystal structure of PfFabZ, the unique beta-hydroxyacyl-ACP dehydratase involved in fatty acid biosynthesis of Plasmodium falciparum. Protein Sci. 2005;14:1570–1580.
  • Tasdemir D, Lack G, Brun R, et al. Inhibition of Plasmodium falciparum fatty acid biosynthesis: evaluation of FabG, FabZ, and FabI as drug targets for flavonoids. J Med Chem. 2006;49:3345–3353.
  • Surolia A, Surolia N, Kumar G, et al. 2-Thioxothiazolidin-4-one compounds and compositions as antimicrobial and antimalrial agents targeting enoyl-ACP reductase of type II fatty acid synthesis pathway and other cell growth pathways. US20080051445Al. 2008.
  • Perozzo R, Kuo M, Sidhu A, et al. Structural elucidation of the specificity of the antibacterial agent triclosan for malarial enoyl acyl carrier protein reductase. J Biol Chem. 2002;277:13106–13114.
  • Schrader FC, Glinca S, Sattler JM, et al. Novel type II fatty acid biosynthesis (FAS II) inhibitors as multistage antimalarial agents. ChemMedChem. 2013;8:442–461.
  • Tasdemir D, Topaloglu B, Perozzo R, et al. Marine natural products from the Turkish sponge Agelas oroides that inhibit the enoyl reductases from Plasmodium falciparum, Mycobacterium tuberculosis and Escherichia coli. Bioorg Med Chem. 2007;15:6834–6845.
  • Sandlin RD, Carter MD, Lee PJ, et al. Use of the NP-40 detergent-mediated assay in discovery of inhibitors of beta-hematin crystallization. Antimicrob Agents Chemother. 2011;55:3363–3369.
  • Saliba KJ, Kirk K. pH regulation in the intracellular malaria parasite, Plasmodium falciparum. H(+) extrusion via a V-type H(+)-ATPase. J Biol Chem. 1999;274:33213–33219.
  • Hayashi M, Yamada H, Mitamura T, et al. Vacuolar H(+)-ATPase localized in plasma membranes of malaria parasite cells, Plasmodium falciparum, is involved in regional acidification of parasitized erythrocytes. J Biol Chem. 2000;275:34353–34358.
  • Nelson N, Harvey WR. Vacuolar and plasma membrane proton-adenosinetriphosphatases. Physiol Rev. 1999;79:361–385.
  • Stevens TH, Forgac M. Structure, function and regulation of the vacuolar (H+)-ATPase. Annu Rev Cell Dev Biol. 1997;13:779–808.
  • Bray PG, Howells RE, Ward SA. Vacuolar acidification and chloroquine sensitivity in Plasmodium falciparum. Biochem Pharmacol. 1992;43:1219–1227.
  • Saliba KJ, Kirk K. H+-coupled pantothenate transport in the intracellular malaria parasite. J Biol Chem. 2001;276:18115–18121.
  • Goldberg DE, Slater AF, Cerami A, et al. Hemoglobin degradation in the malaria parasite Plasmodium falciparum: an ordered process in a unique organelle. Proc Natl Acad Sci USA. 1990;87:2931–2935.
  • Slater AF, Cerami A. Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites. Nature. 1992;355:167–169.
  • Varshney GC, Ganesan K, Shah A, et al. Vacuolar-H+ATPase (V-H+ ATPase) targeting cyclic peptides for treatment of infectious disease such as malaria. WO 2013035107A1. 2013.
  • Ladner RC, Sato AK, Gorzelany J, et al. Phage display-derived peptides as therapeutic alternatives to antibodies. Drug Discov Today. 2004;9:525–529.
  • Wang CJ, Tang JQ, Tao KH, et al. [Screening and identification of mimic epitopes of monoclonal antibodies against hantaan virus using phage display technique]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2004;20:429–432.
  • van Schalkwyk DA, Chan XW, Misiano P, et al. Inhibition of Plasmodium falciparum pH regulation by small molecule indole derivatives results in rapid parasite death. Biochem Pharmacol. 2010;79:1291–1299.
  • van Schalkwyk DA, Saliba KJ, Biagini GA, et al. Loss of pH control in Plasmodium falciparum parasites subjected to oxidative stress. PLoS One. 2013;8:e58933.
  • Doerig CD. Stopping malaria parasites dead in their tracks. Nat Chem Biol. 2008;4:334–335.
  • Moneriz C, Mestres J, Bautista JM, et al. Multi-targeted activity of maslinic acid as an antimalarial natural compound. Febs J. 2011;278:2951–2961.
  • Reker D, Seet M, Pillong M, et al. Deorphaning pyrrolopyrazines as potent multi-target antimalarial agents. Angew Chem Int Ed Engl. 2014;53:7079–7084.
  • Baragana B, Hallyburton I, Lee MC, et al. A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature. 2015;522:315–320.
  • Erath J, Gallego-Delgado J, Xu W, et al. Small-molecule xenomycins inhibit all stages of the Plasmodium life cycle. Antimicrob Agents Chemother. 2015;59:1427–1434.
  • Neufeld EJ. Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood. 2006;107:3436–3441.
  • Scheibel LW, Adler A. Antimalarial activity of selected aromatic chelators. Mol Pharmacol. 1980;18:320–325.
  • Chilengi R, Juma R, Abdallah AM, et al. A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers. Malar J. 2011;10:63.
  • Kiara SM, Okombo J, Masseno V, et al. In vitro activity of antifolate and polymorphism in dihydrofolate reductase of Plasmodium falciparum isolates from the Kenyan coast: emergence of parasites with Ile-164-Leu mutation. Antimicrob Agents Chemother. 2009;53:3793–3798.
  • Nduati E, Diriye A, Ommeh S, et al. Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer. Parasitol Res. 2008;102:1227–1234.
  • Moll GN, van den Eertwegh V, Tournois H, et al. Growth inhibition of Plasmodium falciparum in in vitro cultures by selective action of tryptophan-N-formylated gramicidin incorporated in lipid vesicles. Biochim Biophys Acta. 1991;1062:206–210.
  • Nagaraj G, Uma MV, Shivayogi MS, et al. Antimalarial activities of peptide antibiotics isolated from fungi. Antimicrob Agents Chemother. 2001;45:145–149.
  • Rautenbach M, Vlok NM, Stander M, et al. Inhibition of malaria parasite blood stages by tyrocidines, membrane-active cyclic peptide antibiotics from Bacillus brevis. Biochim Biophys Acta. 2007;1768:1488–1497.
  • Vale N, Aguiar L, Gomes P. Antimicrobial peptides: a new class of antimalarial drugs? Front Pharmacol. 2014;5:275.
  • Joshi M, Shankar VK, Poovaiah T, et al. Discovering novel anti-malarial peptides from the not-coding genome - a working hypothesis. Curr Synthetic Syst Biol. 2013;1. doi:10.4172/2332-0737.1000103
  • Craik DJ, Fairlie DP, Liras S, et al. The future of peptide-based drugs. Chem Biol Drug Des. 2013;81:136–147.
  • Guiguemde WA, Shelat AA, Garcia-Bustos JF, et al. Global phenotypic screening for antimalarials. Chem Biol. 2012;19:116–129.

••A good review article describing the characterization of blood-stage inhibitors of Plasmodium falciparum as well as ongoing research to develop lead molecules and identify their targets.

  • Flannery EL, Fidock DA, Winzeler EA. Using genetic methods to define the targets of compounds with antimalarial activity. J Med Chem. 2013;56:7761–7771.
  • •This article discusses how in vitro evolution of drug-resistant Plasmodium falciparum strains can complement whole-genome analysis for target identification of compounds discovered in whole-cell phenotypic screening.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.