2024
A Divergent Synthesis of Numerous Pyrroloiminoquinone Alkaloids Identifies Promising Antiprotozoal Agents
Barnes G, Magann N, Perrotta D, Hörmann F, Fernandez S, Vydyam P, Choi J, Prudhomme J, Neal A, Le Roch K, Mamoun C, Vanderwal C. A Divergent Synthesis of Numerous Pyrroloiminoquinone Alkaloids Identifies Promising Antiprotozoal Agents. Journal Of The American Chemical Society 2024, 146: 29883-29894. PMID: 39412402, PMCID: PMC11528414, DOI: 10.1021/jacs.4c11897.Peer-Reviewed Original ResearchNatural productsLarock indole synthesisAlkaloid natural productsAmine nucleophilesDivergent synthesisIndole synthesisPyrrolic nitrogenMethoxy groupLead compoundsDrug discoveryCompoundsStructural analogsPlasmodium falciparum</i>SynthesisPyrroloiminoquinoneHuman cytotoxicityMalaria parasitesNucleophilesPyrroleAntiprotozoal agentsAminesMammalian cellsIntermediateIn vitro efficacy of next-generation dihydrotriazines and biguanides against babesiosis and malaria parasites
Vydyam P, Chand M, Gihaz S, Renard I, Heffernan G, Jacobus L, Jacobus D, Saionz K, Shah R, Shieh H, Terpinski J, Zhao W, Cornillot E, Mamoun C. In vitro efficacy of next-generation dihydrotriazines and biguanides against babesiosis and malaria parasites. Antimicrobial Agents And Chemotherapy 2024, 68: e00423-24. PMID: 39136469, PMCID: PMC11373198, DOI: 10.1128/aac.00423-24.Peer-Reviewed Original ResearchTherapeutic indexPlasmodium falciparum</i>Effective therapeutic strategyCausative agent of babesiosisIn vitro efficacyAntiparasitic drugsProtozoan parasitesMalaria parasitesIntraerythrocytic protozoan parasiteTherapeutic strategiesFolate pathwayBroad-spectrum antiparasitic drugStrain HB3Babesia divergensMalariaBabesia duncaniAnimal healthAntifolatesDrugWidespread resistanceCausative agentBiguanideBabesiaBabesiosisBiosynthesis of purines
2023
FT-GPI, a highly sensitive and accurate predictor of GPI-anchored proteins, reveals the composition and evolution of the GPI proteome in Plasmodium species
Sauer L, Canovas R, Roche D, Shams-Eldin H, Ravel P, Colinge J, Schwarz R, Ben Mamoun C, Rivals E, Cornillot E. FT-GPI, a highly sensitive and accurate predictor of GPI-anchored proteins, reveals the composition and evolution of the GPI proteome in Plasmodium species. Malaria Journal 2023, 22: 27. PMID: 36698187, PMCID: PMC9876418, DOI: 10.1186/s12936-022-04430-0.Peer-Reviewed Original ResearchConceptsGPI-APsOrder HaemosporidaGPI-APSequence diversityNew protein candidatesHost cell invasionHost-pathogen interactionsPlasmodium speciesGene duplicationHydrophobic helicesGPI anchorPlasma membraneDeletion eventsProtein candidatesProteomeCell invasionHaemosporidaProteinMalaria parasitesKey functionsDiverse groupSal-1ParasitesMalaria vaccine candidateSpecies
2016
Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond
Van Voorhis WC, Adams JH, Adelfio R, Ahyong V, Akabas MH, Alano P, Alday A, Resto Y, Alsibaee A, Alzualde A, Andrews KT, Avery SV, Avery VM, Ayong L, Baker M, Baker S, Mamoun C, Bhatia S, Bickle Q, Bounaadja L, Bowling T, Bosch J, Boucher LE, Boyom FF, Brea J, Brennan M, Burton A, Caffrey CR, Camarda G, Carrasquilla M, Carter D, Cassera M, Cheng K, Chindaudomsate W, Chubb A, Colon BL, Colón-López DD, Corbett Y, Crowther GJ, Cowan N, D’Alessandro S, Le Dang N, Delves M, DeRisi JL, Du AY, Duffy S, El-Sayed S, Ferdig MT, Robledo J, Fidock DA, Florent I, Fokou PV, Galstian A, Gamo FJ, Gokool S, Gold B, Golub T, Goldgof GM, Guha R, Guiguemde WA, Gural N, Guy RK, Hansen MA, Hanson KK, Hemphill A, van Huijsduijnen R, Horii T, Horrocks P, Hughes TB, Huston C, Igarashi I, Ingram-Sieber K, Itoe MA, Jadhav A, Jensen A, Jensen LT, Jiang RH, Kaiser A, Keiser J, Ketas T, Kicka S, Kim S, Kirk K, Kumar VP, Kyle DE, Lafuente MJ, Landfear S, Lee N, Lee S, Lehane AM, Li F, Little D, Liu L, Llinás M, Loza MI, Lubar A, Lucantoni L, Lucet I, Maes L, Mancama D, Mansour NR, March S, McGowan S, Vera I, Meister S, Mercer L, Mestres J, Mfopa AN, Misra RN, Moon S, Moore JP, da Costa F, Müller J, Muriana A, Hewitt S, Nare B, Nathan C, Narraidoo N, Nawaratna S, Ojo KK, Ortiz D, Panic G, Papadatos G, Parapini S, Patra K, Pham N, Prats S, Plouffe DM, Poulsen SA, Pradhan A, Quevedo C, Quinn RJ, Rice CA, Rizk M, Ruecker A, St. Onge R, Ferreira R, Samra J, Robinett NG, Schlecht U, Schmitt M, Villela F, Silvestrini F, Sinden R, Smith DA, Soldati T, Spitzmüller A, Stamm SM, Sullivan DJ, Sullivan W, Suresh S, Suzuki BM, Suzuki Y, Swamidass SJ, Taramelli D, Tchokouaha LR, Theron A, Thomas D, Tonissen KF, Townson S, Tripathi AK, Trofimov V, Udenze KO, Ullah I, Vallieres C, Vigil E, Vinetz JM, Vinh P, Vu H, Watanabe NA, Weatherby K, White PM, Wilks AF, Winzeler EA, Wojcik E, Wree M, Wu W, Yokoyama N, Zollo PH, Abla N, Blasco B, Burrows J, Laleu B, Leroy D, Spangenberg T, Wells T, Willis PA. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond. PLOS Pathogens 2016, 12: e1005763. PMID: 27467575, PMCID: PMC4965013, DOI: 10.1371/journal.ppat.1005763.Peer-Reviewed Original ResearchConceptsOpen Source Drug DiscoveryDrug discoverySubsequent medicinal chemistry effortsMedicinal chemistry programsMedicinal chemistry effortsMalaria BoxHuman cancer cell line panelMedicinal chemistryChemistry programChemistry effortsMalaria Venture (MMV) Malaria BoxCompound collectionsFamily of structuresCancer cell line panelPhysical compoundsHuman tumor cell linesCompoundsBiological assaysCell line panelPromising candidateValuable starting pointMalaria parasitesImmense potentialLine panelMultiple life cycle stages
2011
Phosphoethanolamine methyltransferases in phosphocholine biosynthesis: functions and potential for antiparasite therapy
Bobenchik AM, Augagneur Y, Hao B, Hoch JC, Mamoun C. Phosphoethanolamine methyltransferases in phosphocholine biosynthesis: functions and potential for antiparasite therapy. FEMS Microbiology Reviews 2011, 35: 609-619. PMID: 21303393, PMCID: PMC4107886, DOI: 10.1111/j.1574-6976.2011.00267.x.Peer-Reviewed Original ResearchConceptsStress-resistant plantsImportant biochemical stepHuman malaria parasiteMethyl donor SAMPhosphocholine biosynthesisN-methyltransferasesFlorida lanceletDependent methyltransferasesNuclear divisionBiochemical stepsDependent methylationBiological functionsGene expressionGenetic characterizationDevelopment of therapiesMalaria parasitesMajor phospholipidsDiverse groupEnzymeSmall moleculesPlantsAntiparasite therapyEukaryotesPhosphoethanolamineMethyltransferases
2008
Disruption of the Plasmodium falciparum PfPMT Gene Results in a Complete Loss of Phosphatidylcholine Biosynthesis via the Serine-Decarboxylase-Phosphoethanolamine-Methyltransferase Pathway and Severe Growth and Survival Defects*
Witola WH, El Bissati K, Pessi G, Xie C, Roepe PD, Mamoun CB. Disruption of the Plasmodium falciparum PfPMT Gene Results in a Complete Loss of Phosphatidylcholine Biosynthesis via the Serine-Decarboxylase-Phosphoethanolamine-Methyltransferase Pathway and Severe Growth and Survival Defects*. Journal Of Biological Chemistry 2008, 283: 27636-27643. PMID: 18694927, PMCID: PMC2562060, DOI: 10.1074/jbc.m804360200.Peer-Reviewed Original ResearchConceptsSDPM pathwayBiosynthesis of phosphatidylcholinePhosphatidylcholine biosynthesisParasite growthMajor membrane phospholipidsHuman malaria parasiteHost serineSerine decarboxylaseGenetic evidenceMethyltransferase enzymeSurvival defectGene resultsYeast cellsMethylation of phosphatidylethanolamineBiosynthesisSynthesis of phosphatidylcholineBiochemical studiesMembrane phospholipidsMalaria parasitesPlasmodium parasitesSevere growthPathwaySignificant defectsParasitesComplete lossGenetic evidence for the essential role of PfNT1 in the transport and utilization of xanthine, guanine, guanosine and adenine by Plasmodium falciparum
Bissati K, Downie MJ, Kim SK, Horowitz M, Carter N, Ullman B, Mamoun C. Genetic evidence for the essential role of PfNT1 in the transport and utilization of xanthine, guanine, guanosine and adenine by Plasmodium falciparum. Molecular And Biochemical Parasitology 2008, 161: 130-139. PMID: 18639591, PMCID: PMC2612043, DOI: 10.1016/j.molbiopara.2008.06.012.Peer-Reviewed Original ResearchConceptsPlasmodium falciparumPurine sourcePurine ring de novoP. falciparum parasitesP. falciparum strainsNon-physiological concentrationsFalciparum parasitesFalciparum strainsMalaria parasitesEpisomal complementationKnockout parasitesParasite strainsGenetic evidencePhysiological concentrationsPurine salvagePfNT1Functional rolePurine uptakeFalciparumAdenosineEssential roleParasitesDe novoGuanineXanthine