Publications

Diamanti E, Steinbach A.M, de Carvalho L.P, Ropponen H.K, Lacour A, Hamid R, Eisa S, Bravo P, Bousis S, Illarionov B, Fischer M, Hamed M.M, Bach N.C, Rottmann M, Held J, Witschel M, Sieber S.A, Hirsch A.K.H. Targeting the Plasmodium falciparum IspE enzyme. ACS Omega. 2024;9:44465-44473. DOI: 10.1021/acsomega.4c06038

Dupouy B, Donzel M, Roignant M, Charital S, Keumoe R, Yamaryo-Botté Y, Feckler A, Bundschuh M, Bordat Y, Rottmann M, Mäser P, Botté C.Y, Blandin S.A, Besteiro S, Davioud-Charvet E. 3-benzylmenadiones and their heteroaromatic analogues target the apicoplast of apicomplexa parasites: synthesis and bioimaging studies. ACS Infect Dis. 2024;10(10):3553-3576. DOI: 10.1021/acsinfecdis.4c00304

Willocx D, Bizzarri L, Alhayek A, Kannan D, Bravo P, Illarionov B, Rox K, Lohse J, Fischer M, Kany A.M, Hahne H, Rottmann M, Witschel M, Odom John A, Hamed M.M, Diamanti E, Hirsch A.K.H. Targeting Plasmodium falciparum IspD in the methyl-d-erythritol phosphate pathway: urea-based compounds with nanomolar potency on target and low-micromolar whole-cell activity. J Med Chem. 2024;67(19):17070-17086. DOI: 10.1021/acs.jmedchem.4c00212

Colina-Vegas L, da Cruz Borges Silva M, de Souza Pereira C, Isis Barros A, Araújo Nobrega J, Navarro M, Rottmann M, D'Alessandro S, Basilico N, Azevedo Batista A, Moreira D.R.M. Antimalarial agents derived from metal-amodiaquine complexes with activity in multiple stages of the Plasmodium life cycle. Chemistry. 2023;29(55):e202301642. DOI: 10.1002/chem.202301642

Mäser P, Bernhard S, Brun R, Burri C, Gagneux S, Hetzel M.W, Kaiser M, Lengeler C, Pluschke G, Reus E, Rottmann M, Utzinger J, Warryn L, Wittlin S, Keiser J. Key contributions by the Swiss Tropical and Public Health Institute towards new and better drugs for tropical diseases. Chimia (Aarau). 2023;77(9):593-606. DOI: 10.2533/chimia.2023.593

Thommen B.T, Dziekan J.M, Achcar F, Tjia S, Passecker A, Buczak K, Gumpp C, Schmidt A, Rottmann M, Grüring C, Marti M, Bozdech Z, Brancucci N.M.B. Genetic validation of PfFKBP35 as an antimalarial drug target. eLife. 2023;12(RP86975). DOI: 10.7554/eLife.86975

Diamanti E, Hamed M.M, Lacour A, Bravo P, Illarionov B, Fischer M, Rottmann M, Witschel M, Hirsch A.K.H. Targeting the IspD enzyme in the MEP pathway: identification of a novel fragment class. ChemMedChem. 2022;17(5):e202100679. DOI: 10.1002/cmdc.202100679

Khandelwal A, Arez F, Alves P.M, Badolo L, Brito C, Fischli C, Fontinha D, Oeuvray C, Prudêncio M, Rottmann M, Wilkins J, Yalkinoglu Ö, Bagchus W.M, Spangenberg T. Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside. Malar J. 2022;21:151. DOI: 10.1186/s12936-022-04171-0

Lowe M.A, Cardenas A, Valentin J.P, Zhu Z, Abendroth J, Castro J.L, Class R, Delaunois A, Fleurance R, Gerets H, Gryshkova V, King L, Lorimer D.D, MacCoss M, Rowley J.H, Rosseels M.L, Royer L, Taylor R.D, Wong M, Zaccheo O, Chavan V.P, Ghule G.A, Tapkir B.K, Burrows J.N, Duffey M, Rottmann M, Wittlin S, Angulo-Barturen I, Jiménez-Díaz M.B, Striepen J, Fairhurst K.J, Yeo T, Fidock D.A, Cowman A.F, Favuzza P, Crespo-Fernandez B, Gamo F.J, Goldberg D.E, Soldati-Favre D, Laleu B, de Haro T. Discovery and characterization of potent, efficacious, orally available antimalarial plasmepsin X inhibitors and preclinical safety assessment of UCB7362. J Med Chem. 2022;65(20):14121-14143. DOI: 10.1021/acs.jmedchem.2c01336

Radohery G.F.R, Walz A, Gumpp C, Cherkaoui-Rbati M.H, Gobeau N, Gower J, Davenport M.P, Rottmann M, McCarthy J.S, Möhrle J.J, Rebelo M, Demarta-Gatsi C, Khoury D.S. Parasite viability as a measure of in vivo drug activity in preclinical and early clinical antimalarial drug assessment. Antimicrob Agents Chemother. 2022;66(7):e0011422. DOI: 10.1128/aac.00114-22

Wicha S.G, Walz A, Cherkaoui-Rbati M.H, Bundgaard N, Kuritz K, Gumpp C, Gobeau N, Möhrle J, Rottmann M, Demarta-Gatsi C. New in vitro interaction-parasite reduction ratio assay for early derisk in clinical development of antimalarial combinations. Antimicrob Agents Chemother. 2022;66(11):e0055622. DOI: 10.1128/aac.00556-22

Ropponen H.K, Bader C.D, Diamanti E, Illarionov B, Rottmann M, Fischer M, Witschel M, Müller R, Hirsch A.K.H. Search for the active ingredients from a 2-aminothiazole DMSO stock solution with antimalarial activity. ChemMedChem. 2021;16:2089–2093. DOI: 10.1002/cmdc.202100067

Ropponen H.K, Diamanti E, Siemens A, Illarionov B, Haupenthal J, Fischer M, Rottmann M, Witschel M, Hirsch A.K.H. Assessment of the rules related to gaining activity against gram-negative bacteria. RSC Med Chem. 2021;12(4):593-601. DOI: 10.1039/d0md00409j

Burgert L, Rottmann M, Wittlin S, Gobeau N, Krause A, Dingemanse J, Möhrle J.J, Penny M.A. Ensemble modeling highlights importance of understanding parasite-host behavior in preclinical antimalarial drug development. Sci Rep. 2020;10:4410. DOI: 10.1038/s41598-020-61304-8

Favuzza P, de Lera Ruiz M, Thompson J.K, Triglia T, Ngo A, Steel R.W.J, Vavrek M, Christensen J, Healer J, Boyce C, Guo Z, Hu M, Khan T, Murgolo N, Zhao L, Penington J.S, Reaksudsan K, Jarman K, Dietrich M.H, Richardson L, Guo K.Y, Lopaticki S, Tham W.H, Rottmann M, Papenfuss T, Robbins J.A, Boddey J.A, Sleebs B.E, Sabroux H.J, McCauley J.A, Olsen D.B, Cowman A.F. Dual plasmepsin-targeting antimalarial agents disrupt multiple stages of the malaria parasite life cycle. Cell Host Microbe. 2020;27(4):642-658 e12. DOI: 10.1016/j.chom.2020.02.005

Müller R, Reddy V.P, Nchinda A.T, Mebrahtu F, Taylor D, Lawrence N, Tanner L, Barnabe M, Eyermann C.J, Zou B, Kondreddi R.R, Lakshminarayana S.B, Rottmann M, Street L.J, Chibale K. Lerisetron analogues with antimalarial properties: synthesis, structure-activity relationship studies, and biological assessment. ACS Omega. 2020;5(12):6967-6982. DOI: 10.1021/acsomega.0c00327

Rottmann M, Jonat B, Gumpp C, Dhingra S.K, Giddins M.J, Yin X, Badolo L, Greco B, Fidock D.A, Oeuvray C, Spangenberg T. Preclinical antimalarial combination study of M5717, a Plasmodium falciparum elongation factor 2 inhibitor, and pyronaridine, a hemozoin formation inhibitor. Antimicrob Agents Chemother. 2020;64(4):e02181-19. DOI: 10.1128/AAC.02181-19

Arez F, Rebelo S.P, Fontinha D, Simao D, Martins T.R, Machado M, Fischli C, Oeuvray C, Badolo L, Carrondo M.J.T, Rottmann M, Spangenberg T, Brito C, Greco B, Prudencio M, Alves P.M. Flexible 3D cell-based platforms for the discovery and profiling of novel drugs targeting Plasmodium hepatic infection. ACS Infect Dis. 2019;5(11):1831-1842. DOI: 10.1021/acsinfecdis.9b00144

Baragaña B, Forte B, Choi R, Nakazawa Hewitt S, Bueren-Calabuig J.A, Pisco J.P, Peet C, Dranow D.M, Robinson D.A, Jansen C, Norcross N.R, Vinayak S, Anderson M, Brooks C.F, Cooper C.A, Damerow S, Delves M, Dowers K, Duffy J, Edwards T.E, Hallyburton I, Horst B.G, Hulverson M.A, Ferguson L, Jiménez-Díaz M.B, Jumani R.S, Lorimer D.D, Love M.S, Maher S, Matthews H, McNamara C.W, Miller P, O'Neill S, Ojo K.K, Osuna-Cabello M, Pinto E, Post J, Riley J, Rottmann M, Sanz L.M, Scullion P, Sharma A, Shepherd S.M, Shishikura Y, Simeons F.R.C, Stebbins E.E, Stojanovski L, Straschil U, Tamaki F.K, Tamjar J, Torrie L.S, Vantaux A, Witkowski B, Wittlin S, Yogavel M, Zuccotto F, Angulo-Barturen I, Sinden R, Baum J, Gamo F.J, Mäser P, Kyle D.E, Winzeler E.A, Myler P.J, Wyatt P.G, Floyd D, Matthews D, Sharma A, Striepen B, Huston C.D, Gray D.W, Fairlamb A.H, Pisliakov A.V, Walpole C, Read K.D, Van Voorhis W.C, Gilbert I.H. Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis. Proc Natl Acad Sci USA. 2019;116(14):7015-7020. DOI: 10.1073/pnas.1814685116

Grogg M, Hilvert D, Ebert M.O, Beck A.K, Seebach D, Kurth F, Dittrich P.S, Sparr C, Wittlin S, Rottmann M, Mäser P. Cell penetration, herbicidal activity, and in-vivo-toxicity of oligo-arginine derivatives and of novel guanidinium-rich compounds derived from the biopolymer cyanophycin. Helvetica Chimica Acta. 2018;101(10):e1800112. DOI: 10.1002/hlca.201800112

Levatić J, Pamić K, Perković I, Uzelac L, Ester K, Kralj M, Kaiser M, Rottmann M, Supek F, Zorc B. Machine learning prioritizes synthesis of primaquine ureidoamides with high antimalarial activity and attenuated cytotoxicity. Eur J Med Chem. 2018;146:651-667. DOI: 10.1016/j.ejmech.2018.01.062

Marti Coma-Cros E, Biosca A, Marques J, Carol L, Urban P, Berenguer D, Riera M.C, Delves M, Sinden R.E, Valle-Delgado J.J, Spanos L, Siden-Kiamos I, Perez P, Paaijmans K, Rottmann M, Manfredi A, Ferruti P, Ranucci E, Fernandez-Busquets X. Polyamidoamine nanoparticles for the oral administration of antimalarial drugs. Pharmaceutics. 2018;10(4):225. DOI: 10.3390/pharmaceutics10040225

Schwertz G, Witschel M.C, Rottmann M, Leartsakulpanich U, Chitnumsub P, Jaruwat A, Amornwatcharapong W, Ittarat W, Schäfer A, Aponte R.A, Trapp N, Chaiyen P, Diederich F. Potent inhibitors of plasmodial serine hydroxymethyltransferase (SHMT) featuring a spirocyclic scaffold. ChemMedChem. 2018;13(9):931-943. DOI: 10.1002/cmdc.201800053

Schwertz G, Frei M.S, Witschel M.C, Rottmann M, Leartsakulpanich U, Chitnumsub P, Jaruwat A, Ittarat W, Schäfer A, Aponte R.A, Trapp N, Mark K, Chaiyen P, Diederich F. Conformational aspects in the design of inhibitors for serine hydroxymethyltransferase (SHMT): biphenyl, aryl sulfonamide, and aryl sulfone motifs. Chemistry. 2017;23(57):14345-14357. DOI: 10.1002/chem.201703244

Schwertz G, Witschel M.C, Rottmann M, Bonnert R, Leartsakulpanich U, Chitnumsub P, Jaruwat A, Ittarat W, Schafer A, Aponte R.A, Charman S.A, White K.L, Kundu A, Sadhukhan S, Lloyd M, Freiberg G.M, Srikumaran M, Siggel M, Zwyssig A, Chaiyen P, Diederich F. Antimalarial inhibitors targeting serine hydroxymethyltransferase (SHMT) with in vivo efficacy and analysis of their binding mode based on X-ray cocrystal structures. J Med Chem. 2017;60(12):4840-4860. DOI: 10.1021/acs.jmedchem.7b00008

Najer A, Wu D, Nussbaumer M.G, Schwertz G, Schwab A, Witschel M.C, Schafer A, Diederich F, Rottmann M, Palivan C.G, Beck H.P, Meier W. An amphiphilic graft copolymer-based nanoparticle platform for reduction-responsive anticancer and antimalarial drug delivery. Nanoscale. 2016;8(31):14858-14869. DOI: 10.1039/c6nr04290b

Bürstner N, Roggo S, Ostermann N, Blank J, Delmas C, Freuler F, Gerhartz B, Hinniger A, Hoepfner D, Liechty B, Mihalic M, Murphy J, Pistorius D, Rottmann M, Thomas J.R, Schirle M, Schmitt E.K. Gift from nature: cyclomarin a kills mycobacteria and malaria parasites by distinct modes of action. ChemBioChem. 2015;16(17):2433-2436. DOI: 10.1002/cbic.201500472

Lakshminarayana S.B, Freymond C, Fischli C, Yu J, Weber S, Goh A, Yeung B.K, Ho P.C, Dartois V, Diagana T.T, Rottmann M, Blasco F. Pharmacokinetics-pharmacodynamics analysis of spiroindolone analogs and KAE609 in a murine malaria model. Antimicrob Agents Chemother. 2015;59(2):1200-1210. DOI: 10.1128/AAC.03274-14

Witschel M.C, Rottmann M, Schwab A, Leartsakulpanich U, Chitnumsub P, Seet M, Tonazzi S, Schwertz G, Stelzer F, Mietzner T, McNamara C, Thater F, Freymond C, Jaruwat A, Pinthong C, Riangrungroj P, Oufir M, Hamburger M, Mäser P, Sanz-Alonso L.M, Charman S, Wittlin S, Yuthavong Y, Chaiyen P, Diederich F. Inhibitors of plasmodial serine hydroxymethyltransferase (SHMT): cocrystal structures of pyrazolopyrans with potent blood- and liver-stage activities. J Med Chem. 2015;58(7):3117-3130. DOI: 10.1021/jm501987h

Brancucci N.M, Bertschi N.L, Zhu L, Niederwieser I, Chin W.H, Wampfler R, Freymond C, Rottmann M, Felger I, Bozdech Z, Voss T.S. Heterochromatin protein 1 secures survival and transmission of malaria parasites. Cell Host Microbe. 2014;16(2):165-176. DOI: 10.1016/j.chom.2014.07.004

Kuhen K.L, Chatterjee A.K, Rottmann M, Gagaring K, Borboa R, Buenviaje J, Chen Z, Francek C, Wu T, Nagle A, Barnes S.W, Plouffe D, Lee M.C, Fidock D.A, Graumans W, Vegte-Bolmer M, Gemert J.V, Wirjanata G, Sebayang B, Marfurt J, Russell B, Suwanarusk R, Price R.N, Nosten F, Tungtaeng A, Gettayacamin M, Sattabongkot J, Taylor J, Walker J.R, Tully D, Patra K.P, Flannery E.L, Vinetz J.M, Renia L, Sauerwein R.W, Winzeler E.A, Glynne R.J, Diagana T.T. KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment and prevention of disease transmission. Antimicrob Agents Chemother. 2014;58(9):5060-5067. DOI: 10.1128/AAC.02727-13

Kunfermann A, Witschel M, Illarionov B, Martin R, Rottmann M, Hoffken H.W, Seet M, Eisenreich W, Knolker H.J, Fischer M, Bacher A, Groll M, Diederich F. Pseudilins: halogenated, allosteric inhibitors of the non-mevalonate pathway enzyme IspD. Angew Chem Int Ed. 2014;53(8):2235-2239. DOI: 10.1002/anie.201309557

Reker D, Seet M, Pillong M, Koch C.P, Schneider P, Witschel M.C, Rottmann M, Freymond C, Brun R, Schweizer B, Illarionov B, Bacher A, Fischer M, Diederich F, Schneider G. Deorphaning pyrrolopyrazines as potent multi-target antimalarial agents. Angew Chem Int Ed Engl. 2014;53(27):7079-7084. DOI: 10.1002/anie.201311162

Urbàn P, Valle-Delgado J.J, Mauro N, Marques J, Manfredi A, Rottmann M, Ranucci E, Ferruti P, Fernàndez-Busquets X. Use of poly(amidoamine) drug conjugates for the delivery of antimalarials to Plasmodium. J Control Release. 2014;177:84-95. DOI: 10.1016/j.jconrel.2013.12.032

Aureggi V, Ehmke V, Wieland J, Schweizer W.B, Bernet B, Bur D, Meyer S, Rottmann M, Freymond C, Brun R, Breit B, Diederich F. Potent inhibitors of malarial aspartic proteases, the plasmepsins, by hydroformylation of substituted 7-azanorbornenes. Chem Eur J. 2013;19(1):155-164. DOI: 10.1002/chem.201202941

Ehmke V, Winkler E, Banner D.W, Haap W, Schweizer W.B, Rottmann M, Kaiser M, Freymond C, Schirmeister T, Diederich F. Optimization of triazine nitriles as rhodesain inhibitors: structure-activity relationships, bioisosteric imidazopyridine nitriles, and X-ray crystal structure analysis with human cathepsin L. ChemMedChem. 2013;8(6):967-975. DOI: 10.1002/cmdc.201300112

Kemp L.E, Rusch M, Adibekian A, Bullen H.E, Graindorge A, Freymond C, Rottmann M, Braun-Breton C, Baumeister S, Porfetye A.T, Vetter I.R, Hedberg C, Soldati-Favre D. Characterization of a serine hydrolase targeted by acyl-protein thioesterase inhibitors in Toxoplasma gondii. J Biol Chem. 2013;288(38):27002-27018. DOI: 10.1074/jbc.M113.460709

McNamara C.W, Lee M.C, Lim C.S, Lim S.H, Roland J, Nagle A, Simon O, Yeung B.K, Chatterjee A.K, McCormack S.L, Manary M.J, Zeeman A.M, Dechering K.J, Kumar T.R, Henrich P.P, Gagaring K, Ibanez M, Kato N, Kuhen K.L, Fischli C, Rottmann M, Plouffe D.M, Bursulaya B, Meister S, Rameh L, Trappe J, Haasen D, Timmerman M, Sauerwein R.W, Suwanarusk R, Russell B, Renia L, Nosten F, Tully D.C, Kocken C.H, Glynne R.J, Bodenreider C, Fidock D.A, Diagana T.T, Winzeler E.A. Targeting Plasmodium PI(4)K to eliminate malaria. Nature. 2013;504(7479):248-253. DOI: 10.1038/nature12782

Ehmke V, Quinsaat J.E, Rivera-Fuentes P, Heindl C, Freymond C, Rottmann M, Brun R, Schirmeister T, Diederich F. Tuning and predicting biological affinity: aryl nitriles as cysteine protease inhibitors. Org Biomol Chem. 2012;10(30):5764-5768. DOI: 10.1039/c2ob00034b

Gemma S, Camodeca C, Sanna Coccone S, Joshi B.P, Bernetti M, Moretti V, Brogi S, Bonache M.C, Savini L, Taramelli D, Basilico N, Parapini S, Rottmann M, Brun R, Lamponi S, Caccia S, Guiso G, Summer R, Martin R, Saponara S, Gorelli B, Novellino E, Campiani G, Butini S. Optimization of 4-aminoquinoline/clotrimazole-based hybrid antimalarials: further structure-activity relationships, in vivo studies, and preliminary toxicity profiling. J Med Chem. 2012;55(15):6948-6967. DOI: 10.1021/jm300802s