Research Topics
| Timothy J EganSummaryAffiliation: University of Cape Town Country: South Africa Publications
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Detail Information
Publications
Haemozoin formationTimothy J Egan
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch, South Africa
Mol Biochem Parasitol 157:127-36. 2008..mansoni and biomimetic studies on the formation of its synthetic counterpart beta-haematin are reviewed. The review also covers methods available for screening compounds for their ability to inhibit beta-haematin formation...- Strategies to reverse drug resistance in malariaTimothy J Egan
Department of Chemistry, University of Cape Town, South Africa
Curr Opin Infect Dis 20:598-604. 2007..Reversal of resistance to old drugs remains one strategy to deal with this problem. This review highlights recent significant findings... 
Recent advances in understanding the mechanism of hemozoin (malaria pigment) formationTimothy J Egan
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
J Inorg Biochem 102:1288-99. 2008..These findings are explored and discussed in the context of earlier studies on beta-hematin formation...- Quinoline antimalarials containing a dibemethin group are active against chloroquinone-resistant Plasmodium falciparum and inhibit chloroquine transport via the P. falciparum chloroquine-resistance transporter (PfCRT)Vincent K Zishiri
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
J Med Chem 54:6956-68. 2011..This constitutes the first example of a dual-function antimalarial for which the ability to inhibit both hemozoin formation and PfCRT has been demonstrated directly... 
Enone- and chalcone-chloroquinoline hybrid analogues: in silico guided design, synthesis, antiplasmodial activity, in vitro metabolism, and mechanistic studiesEric M Guantai
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
J Med Chem 54:3637-49. 2011..Biochemical studies strongly suggested that inhibition of hemozoin formation is the primary mechanism of action of these analogues...- Speciation of ferriprotoporphyrin IX in aqueous and mixed aqueous solution is controlled by solvent identity, pH, and salt concentrationConstance Asher
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
Inorg Chem 48:7994-8003. 2009..The findings permit prediction of the Fe(III)PPIX species present in different mixed solvent systems and in the case of aqueous DMSO at any given pH, concentration, and temperature... - Effects of highly active novel artemisinin-chloroquinoline hybrid compounds on β-hematin formation, parasite morphology and endocytosis in Plasmodium falciparumTzu Shean Feng
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
Biochem Pharmacol 82:236-47. 2011..The hybridization strategy therefore appeared to be borrowing the best from both classes of antimalarials... - Design, synthesis and in vitro antimalarial evaluation of triazole-linked chalcone and dienone hybrid compoundsEric M Guantai
Department of Chemistry, University of Cape Town, South Africa
Bioorg Med Chem 18:8243-56. 2010..Several chalcone-chloroquinoline hybrid compounds were found to be notably active, with compound 8b the most active, exhibiting submicromolar IC(50) values against the D10, Dd2 and W2 strains of Plasmodium falciparum... - Speciation and structure of ferriprotoporphyrin IX in aqueous solution: spectroscopic and diffusion measurements demonstrate dimerization, but not mu-oxo dimer formationKatherine A de Villiers
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch, 7701, South Africa
J Biol Inorg Chem 12:101-17. 2007..Structures for the aqueous dimer are proposed on the basis of molecular dynamics/simulated annealing calculations using a force field previously developed for modeling metalloporphyrins... - A series of structurally simple chloroquine chemosensitizing dibemethin derivatives that inhibit chloroquine transport by PfCRTVincent K Zishiri
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
Eur J Med Chem 46:1729-42. 2011..These compounds may be useful as potential side chains for attaching to a 4,7-dichloroquinoline group in order to generate new resistance-reversing chloroquine analogues with inherent antimalarial activity... - Insights into the role of heme in the mechanism of action of antimalarialsJill M Combrinck
Department of Chemistry and Division of Pharmacology, Department of Medicine, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
ACS Chem Biol 8:133-7. 2013..This study finally provides direct evidence in support of the hemozoin inhibition hypothesis for the mechanism of action of CQ and shows that other quinoline and related antimalarials inhibit cellular hemozoin formation... - Linear free energy relationships predict coordination and π-stacking interactions of small molecules with ferriprotoporphyrin IXDavid Kuter
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
J Inorg Biochem 105:684-92. 2011.... - Haemozoin (beta-haematin) biomineralization occurs by self-assembly near the lipid/water interfaceTimothy J Egan
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
FEBS Lett 580:5105-10. 2006.... - In vitro antimalarial activity of a series of cationic 2,2'-bipyridyl- and 1,10-phenanthrolineplatinum(II) benzoylthiourea complexesTimothy J Egan
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
J Med Chem 47:2926-34. 2004..Cytotoxicity testing of the four most active compounds shows that they exhibit selective activity against malaria parasites with selectivity indices greater than 85. These compounds represent a new family of potential antimalarials... - The crystal structure of halofantrine-ferriprotoporphyrin IX and the mechanism of action of arylmethanol antimalarialsKatherine A de Villiers
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
J Inorg Biochem 102:1660-7. 2008..We propose that salt bridge formation may interrupt formation of the hemozoin precursor dimer formed during the heme detoxification pathway and so account for the strong activity of the two active isomers... - Experimental and time-dependent density functional theory characterization of the UV-visible spectra of monomeric and μ-oxo dimeric ferriprotoporphyrin IXDavid Kuter
Department of Chemistry, Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701 South Africa
Inorg Chem 51:10233-50. 2012..The Q-band and charge transfer bands appear to amalgamate into a mixed low energy envelope consisting of excitations with heavily admixed π→π* and charge transfer transitions... - Neutral lipids associated with haemozoin mediate efficient and rapid β-haematin formation at physiological pH, temperature and ionic compositionMelvin A Ambele
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
Malar J 11:337. 2012..Lipids mediate synthetic haemozoin (β-haematin) formation very efficiently. However, the effect on reaction rates of concentrations of lipid, Fe(III)PPIX and physiologically relevant ions and biomolecules are unknown... - Interactions of quinoline antimalarials with hematin in solutionTimothy J Egan
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
J Inorg Biochem 100:916-26. 2006..This article reviews the spectroscopy, thermodynamics and structures of Fe(III)PPIX-quinoline complexes in solution... - Chloroquine and primaquine: combining old drugs as a new weapon against falciparum malaria?Timothy J Egan
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
Trends Parasitol 22:235-7. 2006..As primaquine and chloroquine are already used together in the treatment of P. vivax, this is potentially a cheap way of reviving and extending the life of chloroquine... - Antiplasmodial, beta-haematin inhibition, antitrypanosomal and cytotoxic activity in vitro of novel 4-aminoquinoline 2-imidazolinesChitalu C Musonda
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
Org Biomol Chem 6:4446-51. 2008..On the other hand, evaluation against a human KB cell line revealed that the compounds were generally non-cytotoxic to the host cells... - A colorimetric high-throughput beta-hematin inhibition screening assay for use in the search for antimalarial compoundsKanyile K Ncokazi
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
Anal Biochem 338:306-19. 2005..The quantitative in vitro antimalarial activities of a set of 13 aminoquinolines and quinoline methanols were found to correlate significantly with beta-hematin inhibition values determined using the assay... - Quinoline antimalarials decrease the rate of beta-hematin formationTimothy J Egan
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
J Inorg Biochem 99:1532-9. 2005..This model can also explain the observation of a sigmoidal dependence of beta-hematin inhibition on drug concentration... - Nucleation of calcium oxalate crystals on an imprinted polymer surface from pure aqueous solution and urineTimothy J Egan
Department of Chemistry, University of Cape Town, Private Bag, 7701 Rondebosch, South Africa
J Biol Inorg Chem 9:195-202. 2004.... - Three 4-aminoquinolines of antimalarial interestSusan A Bourne
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
Acta Crystallogr C 62:o53-7. 2006..Aromatic pi-pi stacking interactions are the only supramolecular interactions seen in all three structures... - Effects of solvent composition and ionic strength on the interaction of quinoline antimalarials with ferriprotoporphyrin IXTimothy J Egan
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
J Inorg Biochem 98:144-52. 2004..The results demonstrate that any successful model of antimalarial drug-Fe(III)PPIX interactions will need to take both solvation and electrostatic factors into account... - Structure-activity relationships in 4-aminoquinoline antiplasmodials. The role of the group at the 7-positionCatherine H Kaschula
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
J Med Chem 45:3531-9. 2002..For the compounds under investigation, the hematin association constant is in turn influenced by the lipophilicity of the group at the 7-position... - Discovering antimalarials: a new strategyTimothy J Egan
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
Chem Biol 9:852-3. 2002..Consequently, new families of potential antimalarials that inhibit HRP-2, a hitherto unexplored drug target, were identified using a novel screening method... - Fate of haem iron in the malaria parasite Plasmodium falciparumTimothy J Egan
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
Biochem J 365:343-7. 2002..Of this, 88+/-9% is in the form of haemozoin. (57)Fe-Mössbauer spectroscopy shows that haemozoin is the only detectable iron species in trophozoites. Electron spectroscopic imaging confirms this conclusion... - Dual-functioning antimalarials that inhibit the chloroquine-resistance transporterTimothy J Egan
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
Future Microbiol 8:475-89. 2013..These are discussed in relation to the mechanism of action of 4-aminoquinolines, chloroquine resistance and resistance reversal... - Physico-chemical aspects of hemozoin (malaria pigment) structure and formationTimothy J Egan
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch, 7701, South Africa
J Inorg Biochem 91:19-26. 2002..Recent literature dealing with the chemical composition, structure and mechanism of formation of hemozoin and its synthetic counterpart, beta-hematin, is reviewed... - Differential effects of quinoline antimalarials on endocytosis in Plasmodium falciparumLindi Roberts
Division of Pharmacology, University of Cape Town Medical School, Observatory 7925, Cape Town, South Africa
Antimicrob Agents Chemother 52:1840-2. 2008..Protease inhibitors moderated hemoglobin perturbations, suggesting a common role for heme binding... - Haemozoin: from melatonin pigment to drug target, diagnostic tool, and immune modulatorThomas Hanscheid
Institute of Molecular Medicine, Lisbon Medical College, Lisbon, Portugal
Lancet Infect Dis 7:675-85. 2007..Finally, haemozoin has a substantial effect on the immune system. Further research is needed to clarify these aspects, many of which are important in clinical practice... - Extracellular lipid droplets promote hemozoin crystallization in the gut of the blood fluke Schistosoma mansoniJuliana B R Corrêa Soares
Instituto de Bioquimica Medica, Programa de Biologia Molecular e Biotecnologia, Universidade Federal do Rio de Janeiro, Cidade Universitaria, Rio de Janeiro, RJ, Brazil
FEBS Lett 581:1742-50. 2007..mansoni. Thus, these data demonstrate that LDs present in the gut lumen of S. mansoni support Hz formation possibly by allowing association of heme to the lipid-water interface of these structures... - Quinoline-resistance reversing agents for the malaria parasite Plasmodium falciparumDonelly A van Schalkwyk
School of Biochemistry and Molecular Biology, Faculty of Science, The Australian National University, Canberra, ACT 0200, Australia
Drug Resist Updat 9:211-26. 2006..This includes a discussion of structure-activity relationships in these compounds and hypotheses on their possible mechanisms of action. The status of current clinical applications is also briefly discussed... - Insights into the mechanism of action of ferroquine. Relationship between physicochemical properties and antiplasmodial activityChristophe Biot
Laboratoire de Catalyse de Lille-UMR CNRS 8010, ENSCL, , , B.P. 90108, 59652, Villeneuve d'Ascq Cedex, France
Mol Pharm 2:185-93. 2005..Increased lipophilicity, differences in geometric and electronic structure, and changes in the N-N distances in FQ compared to CQ probably explain its activity against CQ-resistant parasites... - Turning a chloroquine-resistance reverser into an antimalarialTimothy J Egan
Trends Parasitol 18:344. 2002 - Pigment biocrystallization in Plasmodium falciparumErnst Hempelmann
Trends Parasitol 18:11. 2002 - Porcine small intestine submucosa for soft tissue augmentationJeffrey H Spiegel
Department of Otolaryngology Head and Neck Surgery, Boston University School of Medicine, Boston, Massachusetts 02118, USA
Dermatol Surg 30:1486-90. 2004..Porcine small intestine submucosa was evaluated as a material for soft tissue augmentation in the hairless guinea pig model... - Four aspartic proteases occur in the Plasmodium falciparum food vacuoleTimothy J Egan
Trends Parasitol 18:150. 2002