2024
A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria
Chahine Z, Abel S, Hollin T, Barnes G, Chung J, Daub M, Renard I, Choi J, Vydyam P, Pal A, Alba-Argomaniz M, Banks C, Kirkwood J, Saraf A, Camino I, Castaneda P, Cuevas M, De Mercado-Arnanz J, Fernandez-Alvaro E, Garcia-Perez A, Ibarz N, Viera-Morilla S, Prudhomme J, Joyner C, Bei A, Florens L, Ben Mamoun C, Vanderwal C, Le Roch K. A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria. Science 2024, 385: eadm7966. PMID: 39325875, DOI: 10.1126/science.adm7966.Peer-Reviewed Original ResearchConceptsP. falciparum malariaHumanized mouse modelPlasmodium falciparum</i> strainsIn vivo studiesParasite apicoplastDrug sensitivityTherapeutic profileVesicular traffickingGenomic analysisLipid biogenesisSecretory machineryAsexual replicationGenetic analysisReduced susceptibilityCellular traffickingApicoplast functionStrong efficacyMED6Sexual differentiationHemolytic activityDrug pipelineApicoplastKalihinolTraffickingMalaria
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
2015
Characterization of Plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening
Choi JY, Kumar V, Pachikara N, Garg A, Lawres L, Toh J, Voelker DR, Ben Mamoun C. Characterization of Plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening. Molecular Microbiology 2015, 99: 999-1014. PMID: 26585333, PMCID: PMC4898484, DOI: 10.1111/mmi.13280.Peer-Reviewed Original ResearchConceptsClass of enzymesDevelopment of antimicrobialsYeast genesMembrane biogenesisEukaryotic pathogensProenzyme processingMammalian cellsPhosphatidylserine decarboxylasePSD activityPhospholipid biosynthesisParasite enzymeEssential functionsGenetic studiesMetabolic analysisAmino acidsDecarboxylase enzymePhosphatidylethanolamine synthesisPosition 40Inhibitor screeningEssential roleYeastEnzymePlasmodium falciparumSuitable targetNovel class
2013
Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission
Bobenchik AM, Witola WH, Augagneur Y, Lochlainn L, Garg A, Pachikara N, Choi JY, Zhao YO, Usmani-Brown S, Lee A, Adjalley SH, Samanta S, Fidock DA, Voelker DR, Fikrig E, Mamoun C. Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 18262-18267. PMID: 24145416, PMCID: PMC3831454, DOI: 10.1073/pnas.1313965110.Peer-Reviewed Original ResearchConceptsAsexual replicationGametocyte developmentFunctional complementation assaysPhosphoethanolamine N-methyltransferaseHost serineComplementation assaysMalaria transmissionGenetic diversityPhosphoethanolamine methyltransferaseGametocyte differentiationFemale gametocytesSpecificity of inhibitionMetabolic analysisSynthesis of phosphatidylcholineGametocytogenesisChemical screeningPlasmodium speciesAnopheles mosquitoesN-methyltransferaseLow micromolar rangePathwayReplicationHuman erythrocytesParasitesGlobal burden
1999
A set of independent selectable markers for transfection of the human malaria parasite Plasmodium falciparum
Mamoun C, Gluzman I, Goyard S, Beverley S, Goldberg D. A set of independent selectable markers for transfection of the human malaria parasite Plasmodium falciparum. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8716-8720. PMID: 10411941, PMCID: PMC17582, DOI: 10.1073/pnas.96.15.8716.Peer-Reviewed Original ResearchConceptsSelectable markerPlasmodium gene functionHuman malaria parasite Plasmodium falciparumMalaria parasite Plasmodium falciparumP. falciparum genomeBlasticidin S deaminaseParasite Plasmodium falciparumOnly selectable markerHuman malaria pathogenPlasmid copy numberEssential genesFalciparum genomeGene functionIndependent selectable markersPlasmodium falciparumGenomic informationGenetic manipulationGene promoterNeo expressionFunctional analysisPlasmid replicationTn 5Copy numberDihydrofolate reductaseMalaria pathogen