Reto Brun

University of Münster, Muenster, North Rhine-Westphalia, Germany

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Publications (458)1670.43 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper reports an evaluation of a melamine-nitroheterocycle, a potential lead for further development as an agent against human African trypanosomiasis (HAT). Studies on its efficacy, physicochemical and biopharmaceutical properties and potential for toxicity are described. The compound had previously been shown to possess exceptional activity against Trypanosoma brucei in in vitro assays, comparable to that of melarsoprol. Here, we demonstrate that the compound was also curative in the stringent acute mouse model T. b. rhodesiense STIB 900, when given intraperitoneally at 40 mg/kg. Nevertheless, activity was only moderate when the oral route was used and no cure was obtained when the compound was tested in a stage 2 rodent model of infection. Genotoxic profiling revealed that the compound induces DNA damage, in a mechanism apparently independent from nitro-reduction, and involving introduction of base-pair substitutions (Ames test), possibly caused by oxidative damage of the DNA (Comet test). No significant genotoxicity was observed at the chromosome level (micronucleus assay). The lack of suitable properties for oral and central nervous system uptake and the genotoxic liabilities prevent the progression of this melamine-nitroheterocycle as a drug candidate for HAT. Further modification of the compound is required to improve the pharmacokinetic properties of the molecule and to separate the trypanocidal activity from the toxic potential.
    Antimicrobial Agents and Chemotherapy 07/2014; · 4.57 Impact Factor
  • Angewandte Chemie 07/2014; 126(27).
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    ABSTRACT: Fifteen novel bis-arylimidamide derivatives with various 6-membered (7a-c) and 5-membered (7d-o) heterocyclic rings replacing the terminal pyridyl rings of the lead compound DB766{(2,5-bis[2-i-propoxy-4-(2-pyridylimino)aminophenylfuran]}, were prepared and evaluated versus Trypanosoma cruzi, Leishmania amazonensis, Trypanosoma brucei rhodesiense and Plasmodium falciparum. Compound 7a with pyrimidine replacing the pyridine rings showed good activity versus T. cruzi, T. brucei rhodesiense and P. falciparum (IC50 = 200 nM, 32 nM and 8.5 nM, respectively). Three compounds (7g, 7i, 7j) with thiazole replacing the pyridine rings gave low micromolar (0.17-0.3 μM) IC50 values versus L. amazonensis, however only 7g exhibited an acceptable selectivity index (SI = 27). Compounds 7a, 7j and 7m exhibited potent activity against T. brucei rhodesiense (IC50 = 12-60 nM). Ten of the 15 compounds with pyrimidine, pyrrole, thiazole and imidazole terminal units were highly active against P. falciparum (IC50 = 9-87 nM). Both pyrimidine and pyridine terminal groups are advantageous for anti-T. cruzi activity and several different heterocyclic terminal units are effective versus P. falciparum, both findings merit further investigation.
    European journal of medicinal chemistry. 06/2014; 83C:167-173.
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    ABSTRACT: The discovery of pyrrolopyrazines as potent antimalarial agents is presented, with the most effective compounds exhibiting EC50 values in the low nanomolar range against asexual blood stages of Plasmodium falciparum in human red blood cells, and Plasmodium berghei liver schizonts, with negligible HepG2 cytotoxicity. Their potential mode of action is uncovered by predicting macromolecular targets through avant-garde computer modeling. The consensus prediction method suggested a functional resemblance between ligand binding sites in non-homologous target proteins, linking the observed parasite elimination to IspD, an enzyme from the non-mevalonate pathway of isoprenoid biosynthesis, and multi-kinase inhibition. Further computational analysis suggested essential P. falciparum kinases as likely targets of our lead compound. The results obtained validate our methodology for ligand- and structure-based target prediction, expand the bioinformatics toolbox for proteome mining, and provide unique access to deciphering polypharmacological effects of bioactive chemical agents.
    Angewandte Chemie International Edition in English 06/2014; · 13.45 Impact Factor
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    ABSTRACT: The regioselective insertion of nitrogen in a bicyclic octanone skeleton is reported. The structure was established by a single crystal structure analysis. The antiprotozoal activities of lactames and their reduction products were determined and discussed. Graphical Abstract
    Monatshefte fuer Chemie/Chemical Monthly 06/2014; · 1.63 Impact Factor
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    ABSTRACT: African sleeping sickness is a neglected tropical disease transmitted by tsetse flies. New and better drugs are still needed especially for its second stage, which is fatal if untreated. 28DAP010, a dipyridylbenzene analogue of DB829, is the second simple diamidine found to cure mice with central nervous system infections by a parenteral route of administration. 28DAP010 showed similar efficacy to DB829 in dose response studies in mouse models of first and second stage African sleeping sickness. The in vitro time to kill, determined by microcalorimetry and the parasite clearance time in mice, were shorter for 28DAP010 than for DB829. No cross-resistance was observed between 28DAP010 and pentamidine on the tested T. b. gambiense isolates from melarsoprol-refractory patients. 28DAP010 is the second promising preclinical candidate among the diamidines for the treatment of second stage African sleeping sickness.
    Antimicrobial Agents and Chemotherapy 05/2014; · 4.57 Impact Factor
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    ABSTRACT: Human African trypanosomiasis (HAT), a neglected tropical disease, is fatal without treatment. Pentamidine, a cationic diamidine, has been used to treat first stage (hemolymphatic) HAT since the 1940s, but it is ineffective against second stage (meningoencephalitic or CNS) infection. Novel diamidines (DB75, DB820, and DB829) have shown promising efficacy in both mouse and monkey models of first stage HAT. However, only DB829 cured animals with second stage infection. In this study, we aimed to determine mechanisms underlying the differential efficacy of these diamidines against HAT by conducting a comprehensive pharmacokinetic characterization. This included the determination of metabolic stability in liver microsomes, permeability across MDCK and MDR1-MDCK cell monolayers, interaction with the efflux transporter MDR1 (P-glycoprotein 1 or P-gp), drug binding in plasma and brain, and plasma and brain concentration-time profiles after a single dose in mice. Results showed that DB829, an aza diamidine, had the highest systemic exposure and brain-to-plasma ratio, whereas pentamidine and DB75 were the lowest. None of these diamidines was a P-gp substrate and the binding of each to plasma proteins and brain differed greatly. The brain-to-plasma ratio best predicted the relative efficacy of these diamidines in mice with second stage infection. In conclusion, pharmacokinetics and CNS penetration influenced the in vivo efficacy of cationic diamidines against first and second stage HAT and should be considered when developing CNS-active antitrypanosomal diamidines.
    Antimicrobial Agents and Chemotherapy 05/2014; · 4.57 Impact Factor
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    ABSTRACT: The causative agents of the parasitic disease human African trypanosomiasis belong to the family of trypanosomatids. These parasitic protozoa exhibit a unique thiol redox metabolism that is based on the flavoenzyme trypanothione reductase (TR). TR was identified as a potential drug target and features a large active site that allows a multitude of possible ligand orientations, which renders rational structure-based inhibitor design highly challenging. Herein we describe the synthesis, binding properties, and kinetic analysis of a new series of small-molecule inhibitors of TR. The conjunction of biological activities, mutation studies, and virtual ligand docking simulations led to the prediction of a binding mode that was confirmed by crystal structure analysis. The crystal structures revealed that the ligands bind to the hydrophobic wall of the so-called “mepacrine binding site”. The binding conformation and potency of the inhibitors varied for TR from Trypanosoma brucei and T. cruzi.
    ChemMedChem 04/2014; · 2.84 Impact Factor
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    ABSTRACT: In the present study, twenty one 1-aryl-6-hydroxy-1,2,3,4-tetrahydroisoquinoline (THIQ) analogues were synthesized by based-catalyzed Pictet-Spengler reaction, and tested in vitro against P. falciparum using the [3H]hypoxanthine incorporation assay. Two compounds were found to be inactive while seventeen compounds displayed moderate antiplasmodial activity and two compounds were found to be highly active (IC50 < 0.2 μg/ml). The two highly active compounds, 1-(4-chlorophenyl)-6-hydroxyl-1,2,3,4-tetrahydroisoquinoline and 6-hydroxyspiro[1,2,3,4-tetrahydroisoquinoline-1:1’-cyclohexane], also displayed low cytotoxicity, against rat skeletal myoblast cells, with CC50 values of 257.6 and 174.2 μM respectively. These results justify further investigation of simple 1-aryl-1,2,3,4-tetrahydroisoquinolines as potential anti-malarial agents.
    RSC Advances 04/2014; 4:22856-22865. · 3.71 Impact Factor
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    ABSTRACT: SUMMARY Chagas disease (CD) is caused by the intracellular protozoan parasite Trypanosoma cruzi and affects more than 10 million people in poor areas of Latin America. There is an urgent need for alternative drugs with better safety, broader efficacy, lower costs and shorter time of administration. Thus the biological activity of viniconazole, a chloroaryl-substituted imidazole was investigated using in vitro and in vivo screening models of T. cruzi infection. Ultrastructural findings demonstrated that the most frequent cellular damage was associated with plasma membrane (blebs and shedding events), Golgi (swelling aspects) and the appearance of large numbers of vacuoles suggesting an autophagic process. Our data demonstrated that although this compound is effective against bloodstream and intracellular forms (16 and 24 μ m, respectively) in vitro, it does not present in vivo efficacy. Due to the urgent need for novel agents against T. cruzi, the screening of natural and synthetic products must be further supported with the aim of finding more selective and affordable drugs for CD.
    Parasitology 03/2014; 141(3):367-373. · 2.36 Impact Factor
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    ABSTRACT: A new series of 4-aminobicyclo[2.2.2]octan-2-yl 4-aminobutanoates have been prepared. Their activities against the multiresistant K1 strain of Plasmodium falciparum and Trypanosoma brucei rhodesiense were determined and compared with the results for ethanoate and propanoate analogs. Several structure–activity relationships were detected. The antiprotozoal activities were influenced by the kind of both amino substituents and by the chain length of the acid moiety. The butanoates exhibited higher antiplasmodial potency than their analogs with shorter chain length. Representative compounds of the propanoate and butanoate series were the most active antitrypanosomal compounds. Graphical abstract
    Monatshefte fuer Chemie/Chemical Monthly 02/2014; 145(2). · 1.63 Impact Factor
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    ABSTRACT: A significant improvement in the treatment of trypanosomiases has been achieved with the recent development of nifurtimox-eflornithine combination therapy (NECT). As an alternative to drug combinations and as a means to overcome most of the antitrypanosomatid drug discovery challenges, a multitarget drug design strategy has been envisaged. To begin testing this hypothesis, we designed and developed a series of quinone-coumarin hybrids against glyceraldehyde-3-phosphate dehydrogenase/trypanothione reductase (GAPDH/TR). These enzymes belong to metabolic pathways that are vital to Trypanosoma brucei and Trypanosoma cruzi, and have thus been considered promising drug targets. The synthesized molecules were characterized for their dual-target antitrypanosomal profile, both in enzyme assays and in in vitro parasite cultures. The merged derivative 2-{[3-(3-dimethylaminopropoxy)-2-oxo-2H-chromen-7-yl]oxy}anthracene-1,4-dione (10) showed an IC50 value of 5.4 μM against TbGAPDH and a concomitant Ki value of 2.32 μM against TcTR. Notably, 2-{4-[6-(2-dimethylaminoethoxy)-2-oxo-2H-chromen-3-yl]phenoxy}anthracene-1,4-dione (compound 6) displayed a remarkable EC50 value for T. brucei parasites (0.026 μM) combined with a very low cytotoxicity toward mammalian L6 cells (7.95 μM). This promising low toxicity of compound 6 might be at least partially due to the fact that it does not interfere with human glutathione reductase.
    ChemMedChem 01/2014; · 2.84 Impact Factor
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    ABSTRACT: The isolation and structural characterization of three new heterocyclic and macrocyclic peptides, balgacyclamides A-C, from Microcystis aeruginosa EAWAG 251 are reported. The constitutions were determined by 2D-NMR methods and mass spectrometry, and the configurations were assigned after ozonolysis and hydrolysis by HPLC-MS methods using Marfey's method as well as GC-MS using authentic standards. Balgacyclamides A and B were active against Plasmodium falciparum K1 in the low micromolar range, while displaying low toxicity to rat myoblasts.
    Journal of Natural Products 01/2014; · 3.29 Impact Factor
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    ABSTRACT: Cynaropicrin is a guaianolide sesquiterpene lactone with a 5-7-5 tricyclic skeleton, four exo-olefins, and two hydroxyl groups. Recently, it was found that the compound is a potent in vitro and in vivo inhibitor of the protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis (HAT; sleeping sickness). In this Letter, chemical derivatization of cynaropicrin and the structure-activity-relationship (SAR) study against T. brucei is described.
    Bioorganic & medicinal chemistry letters 01/2014; · 2.65 Impact Factor
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    ABSTRACT: In the course of our ongoing screening of plants of the family Asteraceae for antiprotozoal activity, a CH2Cl2-extract from the flowering aerial parts of Achillea ptarmica L. (sneezewort yarrow) was found to be active in vitro against Trypanosoma brucei rhodesiense (IC50 = 0.67 µg/mL) and Plasmodium falciparum (IC50 = 6.6 μg/mL). Bioassay guided fractionation led to the isolation and identification of five alkamides from the most active fractions. Pellitorine and 8,9-Z-dehyropellitorine are the main components of the extract. Beside these olefinic acid amides, four alkamides with diene-diyne structures were isolated. All alkamides were tested for antiprotozoal activity in vitro. Pellitorine was the most active compound so far within this study against P. falciparum (IC50 = 3.3 µg/mL), while 8,9-Z-dehydropellitorine was most active against T. b. rhodesiense (IC50 = 2.0 µg/mL). The activity of pure pellitorine against Plasmodium is higher than that of the crude extract and thus explains the activity of the latter. None of the isolated alkamides, however, was as active against T. b. rhodesiense as the crude extract whose antitrypanosomal activity must therfore be due to a synergistic effect of the isolated compounds or to more active yet to be identified constituents.
    Molecules (Basel, Switzerland). 01/2014; 19(5):6428-38.
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    ABSTRACT: Buxus sempervirens L. (European Box, Buxaceae) has been used in ethnomedicine to treat malaria. In the course of our screening of plant extracts for antiprotozoal activity, a CH2Cl2 extract from leaves of B. sempervirens showed selective in vitro activity against Plasmodium falciparum (IC50 = 2.79 vs. 20.2 µg/mL for cytotoxicity against L6 rat cells). Separation of the extract by acid/base extraction into a basic and a neutral non-polar fraction led to a much more active and even more selective fraction with alkaloids while the fraction of non-polar neutral constituents was markedly less active than the crude extract. Thus, the activity of the crude extract could clearly be attributed to alkaloid constituents. Identification of the main triterpene-alkaloids and characterization of the complex pattern of this alkaloid fraction was performed by UHPLC/+ESI-QTOF-MS analyses. ESI-MS/MS target-guided larger scale preparative separation of the alkaloid fraction was performed by 'spiral coil-countercurrent chromatography'. From the most active subfraction, the cycloartane alkaloid O-tigloylcyclovirobuxeine-B was isolated and evaluated for antiplasmodial activity which yielded an IC50 of 0.455 µg/mL (cytotoxicity against L6 rat cells: IC50 = 9.38 µg/mL). O-tigloylcyclovirobuxeine-B is thus most significantly responsible for the high potency of the crude extract.
    Molecules (Basel, Switzerland). 01/2014; 19(5):6184-6201.
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    ABSTRACT: In continuation of our earlier study on the in vitro antiprotozoal activity of 40 natural sesquiterpene lactones (STLs), we extended the set of tested compounds from our laboratories to 59. On the basis of this extended data set, further enriched by literature data for 10 compounds tested under the same conditions, our QSAR analyses for activity against T. brucei rhodesiense (etiologic agent of Human African Trypanosomiasis or Sleeping Sickness) were continued and the QSAR model thus obtained with 69 structures was used to predict the activity of a virtual library of 1750 STL structures. As a major result from these calculations furanoheliangolide-type compounds, a subclass of STLs hitherto untested against T. brucei rhodesiense, were predicted to have an exceptionally high level of in vitro activity. Four representative compounds of this type, goyazensolide, 4,5-dihydro-2' ,3' -epoxy-15-deoxygoyazensolide, budlein A and 4,15-isoatriplicolide tiglate, were therefore tested. They displayed IC50 values of 0.07, 0.20 and 0.07 and 0.015 μM, respectively, so that the in silico-prediction was experimentally confirmed. 4,15-isoatriplicolide tiglate is the most potent STL against T. b. rhodesiense found up to present. Furanoheliangolide STLs were thus indentified as interesting leads against this parasite which deserve more detailed investigations.
    Antimicrobial Agents and Chemotherapy 01/2014; 58(1):325-332. · 4.57 Impact Factor
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    ABSTRACT: A productive synthesis of benzo[a]phenoxazine derivative SSJ-183 (1), a promising lead for antimalarial agents, was developed using a one pot procedure. Furthermore, N-deethylated metabolite 3 and bis-N,N-deethylated metabolite 4 were synthesized by the application of the method. The metabolites 3 and 4 showed comparable and ∼2-fold increased activities against drug-sensitive and drug-resistant Plasmodium falciparum parasites.
    Bioorganic & Medicinal Chemistry. 01/2014;
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    ABSTRACT: In an in vitro screen of 206 extracts from South African plants, the CH2Cl2/MeOH (1:1) stem extract of Drypetes gerrardii Hutch. var gerrardii (Putranjivaceae) inhibited Plasmodium falciparum and Leishmania donovani (IC50s of 0.50 and 7.31 μg/ml, respectively). In addition, the CH2Cl2/MeOH (1:1) extract of the leaves showed activity against Trypanosoma brucei rhodesiense (IC50 of 12.1 μg/ml). The active constituents were tracked by HPLC-based activity profiling, and isolated by preparative and semi-preparative RP-HPLC chromatography. Their structures were established by HRESIMS, and 1D and 2D NMR (1H, 13C, COSY, HMBC, HSQC, and NOESY). From the stem extract, a new phenanthrenone derivative, drypetenone D (1), and a phenanthrenone heterodimer, drypetenone E (2), were isolated. Compound 1 showed potent in vitro activity against P. falciparum (IC50 of 0.9 μM) with a selectivity index (SI) of 71, as calculated from cytotoxicity data for L-6 cells. These data qualified 1 for in vivo assessment in the Plasmodium berghei mouse model, but the compound turned out to be inactive. Compound 2 also exhibited good in vitro antiplasmodial activity (IC50 of 2.0 μM) and selectivity (SI 31). From the leaf extract, the saponin putranoside A (3) was isolated and identified. Compound 3 showed weak in vitro trypanocidal activity, with an IC50 of 18.0 μM, and a SI of 4.
    Phytochemistry Letters 01/2014; · 1.18 Impact Factor
  • European Journal of Medicinal Chemistry. 01/2014; 83:167–173.

Publication Stats

6k Citations
1,670.43 Total Impact Points

Institutions

  • 2009–2014
    • University of Münster
      • Institute of Pharmaceutical Biology and Phytochemistry
      Muenster, North Rhine-Westphalia, Germany
    • Kenya Agricultural Research Institute
      Nairoba, Nairobi Area, Kenya
    • Institute of Primate Research
      Nairoba, Nairobi Area, Kenya
    • University of Greifswald
      • Institute of Pharmacy
      Greifswald, Mecklenburg-Vorpommern, Germany
    • Yale University
      • Department of Ecology and Evolutionary Biology
      New Haven, CT, United States
  • 1999–2014
    • Universität Basel
      • • Group of Pharmaceutical Biology
      • • Department of Pharmaceutical Sciences
      • • Swiss Tropical and Public Health Institute (Swiss TPH)
      Bâle, Basel-City, Switzerland
  • 1996–2014
    • Swiss Tropical and Public Health Institute
      • Department of Epidemiology and Public Health
      Bâle, Basel-City, Switzerland
  • 2013
    • St. Jude Children's Research Hospital
      • Department of Chemical Biology and Therapeutics
      Memphis, TN, United States
  • 2011–2013
    • Shahid Beheshti University
      • Department of Phytochemistry
      Teheran, Tehrān, Iran
    • Ankara University
      • Faculty of Pharmacy
      Ankara, Ankara, Turkey
    • Northeast Institute of Geography and Agroecology
      • Institute of Microbiology
      Beijing, Beijing Shi, China
    • National Institute of Malaria Research
      Old Delhi, NCT, India
    • Yeditepe University
      • Faculty of Pharmacy
      İstanbul, Istanbul, Turkey
    • Soochow University (PRC)
      • Key Laboratory of Organic Synthesis of Jiangsu Province
      Suzhou, Jiangsu Sheng, China
    • Monash University (Australia)
      • Centre for Drug Candidate Optimisation
      Melbourne, Victoria, Australia
    • Mansoura University
      • Department of Chemistry
      Ṭalkha, Muhafazat ad Daqahliyah, Egypt
    • Cairo University
      • Faculty of Pharmacy
      Cairo, Muhafazat al Qahirah, Egypt
  • 2008–2013
    • University of Bologna
      • Department of Pharmacy and Biotechnology FaBiT
      Bologna, Emilia-Romagna, Italy
    • ETH Zurich
      • Laboratory of Organic Chemistry
      Zürich, ZH, Switzerland
    • Universidad de Panamá
      • Facultad de Farmacia
      Chitré, Provincia de Herrera, Panama
  • 2004–2013
    • University of North Carolina at Chapel Hill
      • Department of Pathology and Laboratory Medicine
      Chapel Hill, NC, United States
    • Karl-Franzens-Universität Graz
      • • Institute of Pharmaceutical Sciences
      • • Department of Pharmaceutical Chemistry
      Graz, Styria, Austria
  • 2002–2013
    • Georgia State University
      • • Department of Chemistry
      • • Center for Biotechnology and Drug Design
      Atlanta, GA, United States
    • University of Botswana
      • Department of Chemistry
      Gaborone, South East District, Botswana
  • 2012
    • BASF SE
      Ludwigshafen, Rheinland-Pfalz, Germany
    • Mazandaran University of Medical Sciences
      • Faculty of Pharmacy
      Āmol, Mazandaran, Iran
  • 2008–2012
    • University of Illinois at Chicago
      • Department of Medicinal Chemistry and Pharmacognosy
      Chicago, IL, United States
  • 2004–2012
    • The Ohio State University
      • Division of Medicinal Chemistry and Pharmacognosy
      Columbus, OH, United States
  • 2002–2012
    • University of Wuerzburg
      • Institute of Organic Chemistry
      Würzburg, Bavaria, Germany
  • 2008–2011
    • Hoshi University
      • Institute of Medicinal Chemistry
      Shinagawa, Tōkyō, Japan
  • 2007–2011
    • University of Dundee
      • College of Life Sciences
      Dundee, SCT, United Kingdom
    • Centro Internacional de Entrenamiento e Investigaciones Médicas
      Santiago de Cali, Valle del Cauca, Colombia
    • University of Nebraska Medical Center
      • College of Pharmacy
      Omaha, Nebraska, United States
    • Venezuelan Institute for Scientific Research
      • Laboratorio de Química Biológica
      Caracas, Distrito Federal, Venezuela
  • 1999–2011
    • Cardiff University
      Cardiff, Wales, United Kingdom
  • 2010
    • University of California, San Francisco
      San Francisco, California, United States
    • University of Wales
      Cardiff, Wales, United Kingdom
    • National Center for Genetic Engineering and Biotechnology (BIOTEC)
      Bang Kadi, Pathum Thani, Thailand
    • Gazi University
      • Faculty of Pharmacy
      Ankara, Ankara, Turkey
  • 2008–2010
    • École Polytechnique Fédérale de Lausanne
      • Laboratoire de synthèse et de catalyse inorganique
      Lausanne, VD, Switzerland
  • 2007–2009
    • University of Geneva
      • Department of Pharmaceutical Biochemistry
      Genève, GE, Switzerland
  • 2006–2009
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
    • University of Zurich
      • Institut für Organische Chemie
      Zürich, ZH, Switzerland
  • 2005–2009
    • University of Antwerp
      • • Departement Chemie
      • • Departement Farmaceutische Wetenschappen
      Antwerpen, VLG, Belgium
    • University of Nebraska at Omaha
      • College of Pharmacy
      Omaha, NE, United States
    • Julphar School of Pharmacy
      Louisiana, United States
  • 2004–2009
    • Spanish National Research Council
      • Instituto de Química Médica
      Madrid, Madrid, Spain
  • 1997–2009
    • Universität Bern
      • • Institut für Zellbiologie
      • • Institut für Biochemie und Molekulare Medizin
      Bern, BE, Switzerland
  • 2007–2008
    • Athens State University
      Athens, Alabama, United States
  • 2006–2007
    • University of London
      • The School of Pharmacy
      London, ENG, United Kingdom
  • 2003–2007
    • University of Glasgow
      • Institute of Infection, Immunity and Inflammation
      Glasgow, Scotland, United Kingdom
    • University of Tuebingen
      Tübingen, Baden-Württemberg, Germany
  • 2005–2006
    • Tohoku University
      • Graduate School of Pharmaceutical Sciences
      Sendai-shi, Miyagi-ken, Japan
  • 2004–2005
    • Hacettepe University
      • Department of Pharmacognosy
      Ankara, Ankara, Turkey
  • 2000
    • University of Peradeniya
      • Department of Chemistry
      Kandy, Central Province, Sri Lanka
    • University Hospital of Lausanne
      Lausanne, Vaud, Switzerland