Timothy J Egan

Summary

Affiliation: University of Cape Town
Country: South Africa

Publications

  1. ncbi Haemozoin formation
    Timothy J Egan
    Department of Chemistry, University of Cape Town, Private Bag, Rondebosch, South Africa
    Mol Biochem Parasitol 157:127-36. 2008
  2. doi Dual-functioning antimalarials that inhibit the chloroquine-resistance transporter
    Timothy J Egan
    Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
    Future Microbiol 8:475-89. 2013
  3. ncbi Strategies to reverse drug resistance in malaria
    Timothy J Egan
    Department of Chemistry, University of Cape Town, South Africa
    Curr Opin Infect Dis 20:598-604. 2007
  4. doi Recent advances in understanding the mechanism of hemozoin (malaria pigment) formation
    Timothy J Egan
    Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
    J Inorg Biochem 102:1288-99. 2008
  5. doi 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
  6. pmc Enone- and chalcone-chloroquinoline hybrid analogues: in silico guided design, synthesis, antiplasmodial activity, in vitro metabolism, and mechanistic studies
    Eric M Guantai
    Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
    J Med Chem 54:3637-49. 2011
  7. ncbi In vitro antimalarial activity, β-haematin inhibition and structure-activity relationships in a series of quinoline triazoles
    Mukesh C Joshi
    Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
    Eur J Med Chem 69:338-47. 2013
  8. doi Speciation of ferriprotoporphyrin IX in aqueous and mixed aqueous solution is controlled by solvent identity, pH, and salt concentration
    Constance Asher
    Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
    Inorg Chem 48:7994-8003. 2009
  9. doi A series of structurally simple chloroquine chemosensitizing dibemethin derivatives that inhibit chloroquine transport by PfCRT
    Vincent K Zishiri
    Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
    Eur J Med Chem 46:1729-42. 2011
  10. doi Design, synthesis and in vitro antimalarial evaluation of triazole-linked chalcone and dienone hybrid compounds
    Eric M Guantai
    Department of Chemistry, University of Cape Town, South Africa
    Bioorg Med Chem 18:8243-56. 2010

Collaborators

Detail Information

Publications44

  1. ncbi Haemozoin formation
    Timothy 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...
  2. doi Dual-functioning antimalarials that inhibit the chloroquine-resistance transporter
    Timothy 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...
  3. ncbi Strategies to reverse drug resistance in malaria
    Timothy 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...
  4. doi Recent advances in understanding the mechanism of hemozoin (malaria pigment) formation
    Timothy 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...
  5. doi 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...
  6. pmc Enone- and chalcone-chloroquinoline hybrid analogues: in silico guided design, synthesis, antiplasmodial activity, in vitro metabolism, and mechanistic studies
    Eric 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...
  7. ncbi In vitro antimalarial activity, β-haematin inhibition and structure-activity relationships in a series of quinoline triazoles
    Mukesh C Joshi
    Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
    Eur J Med Chem 69:338-47. 2013
    ..The findings demonstrate the feasibility of producing hydrophilic analogues with strong activity and low cross-resistance with chloroquine...
  8. doi Speciation of ferriprotoporphyrin IX in aqueous and mixed aqueous solution is controlled by solvent identity, pH, and salt concentration
    Constance 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...
  9. doi A series of structurally simple chloroquine chemosensitizing dibemethin derivatives that inhibit chloroquine transport by PfCRT
    Vincent 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...
  10. doi Design, synthesis and in vitro antimalarial evaluation of triazole-linked chalcone and dienone hybrid compounds
    Eric 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...
  11. doi Effects of highly active novel artemisinin-chloroquinoline hybrid compounds on β-hematin formation, parasite morphology and endocytosis in Plasmodium falciparum
    Tzu 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...
  12. doi Linear free energy relationships predict coordination and π-stacking interactions of small molecules with ferriprotoporphyrin IX
    David Kuter
    Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
    J Inorg Biochem 105:684-92. 2011
    ....
  13. ncbi Speciation and structure of ferriprotoporphyrin IX in aqueous solution: spectroscopic and diffusion measurements demonstrate dimerization, but not mu-oxo dimer formation
    Katherine 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...
  14. doi Structure-activity relationships for ferriprotoporphyrin IX association and β-hematin inhibition by 4-aminoquinolines using experimental and ab initio methods
    Samkele Nsumiwa
    Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
    Bioorg Med Chem 21:3738-48. 2013
    ..The upshot is that the correlations imply that considerably more hydrophilic hemozoin inhibitors are feasible...
  15. ncbi Haemozoin (beta-haematin) biomineralization occurs by self-assembly near the lipid/water interface
    Timothy J Egan
    Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
    FEBS Lett 580:5105-10. 2006
    ....
  16. pmc Insights into the role of heme in the mechanism of action of antimalarials
    Jill 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...
  17. ncbi Synthesis, characterization, antiparasitic and cytotoxic evaluation of thioureas conjugated to polyamine scaffolds
    Tameryn Stringer
    Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
    Eur J Med Chem 69:90-8. 2013
    ..The quinoline compounds were also found to be more cytotoxic compared to the ferrocenyl compounds. Compound 6 displays good cytotoxicity against WHCO1 oesophageal cancer cells...
  18. doi The crystal structure of halofantrine-ferriprotoporphyrin IX and the mechanism of action of arylmethanol antimalarials
    Katherine 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...
  19. ncbi In vitro antimalarial activity of a series of cationic 2,2'-bipyridyl- and 1,10-phenanthrolineplatinum(II) benzoylthiourea complexes
    Timothy 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...
  20. pmc Neutral lipids associated with haemozoin mediate efficient and rapid β-haematin formation at physiological pH, temperature and ionic composition
    Melvin 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...
  21. ncbi Experimental and time-dependent density functional theory characterization of the UV-visible spectra of monomeric and μ-oxo dimeric ferriprotoporphyrin IX
    David 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...
  22. ncbi Interactions of quinoline antimalarials with hematin in solution
    Timothy 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...
  23. ncbi 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...
  24. ncbi A colorimetric high-throughput beta-hematin inhibition screening assay for use in the search for antimalarial compounds
    Kanyile 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...
  25. ncbi Effects of solvent composition and ionic strength on the interaction of quinoline antimalarials with ferriprotoporphyrin IX
    Timothy 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...
  26. doi Antiplasmodial, beta-haematin inhibition, antitrypanosomal and cytotoxic activity in vitro of novel 4-aminoquinoline 2-imidazolines
    Chitalu 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...
  27. ncbi Quinoline antimalarials decrease the rate of beta-hematin formation
    Timothy 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...
  28. ncbi Nucleation of calcium oxalate crystals on an imprinted polymer surface from pure aqueous solution and urine
    Timothy J Egan
    Department of Chemistry, University of Cape Town, Private Bag, 7701 Rondebosch, South Africa
    J Biol Inorg Chem 9:195-202. 2004
    ....
  29. ncbi Structure-activity relationships in 4-aminoquinoline antiplasmodials. The role of the group at the 7-position
    Catherine 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...
  30. ncbi Discovering antimalarials: a new strategy
    Timothy 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...
  31. ncbi Three 4-aminoquinolines of antimalarial interest
    Susan 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...
  32. pmc Fate of haem iron in the malaria parasite Plasmodium falciparum
    Timothy 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...
  33. doi Multiple spectroscopic and magnetic techniques show that chloroquine induces formation of the μ-oxo dimer of ferriprotoporphyrin IX
    David Kuter
    Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa
    J Inorg Biochem 133:40-9. 2014
    ..The findings suggest the formation of a 2:4 CQ:Fe(III)PPIX complex in aqueous solution at pH7.4...
  34. ncbi Kojic acid derived hydroxypyridinone-chloroquine hybrids: Synthesis, crystal structure, antiplasmodial activity and β-haematin inhibition
    Warren Andrew Andayi
    Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
    Bioorg Med Chem Lett 24:3263-7. 2014
    ..004μM; IC50(K1)=0.03μM) and had the best β-haematin inhibition activity (0.07 IC50 equiv vs 1.91 IC50 equiv for chloroquine). One compound 8c was found to be equipotent in both strains (IC50=0.04μM). ..
  35. ncbi Physico-chemical aspects of hemozoin (malaria pigment) structure and formation
    Timothy 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...
  36. ncbi Turning a chloroquine-resistance reverser into an antimalarial
    Timothy J Egan
    Trends Parasitol 18:344. 2002
  37. ncbi Insights into the mechanism of action of ferroquine. Relationship between physicochemical properties and antiplasmodial activity
    Christophe Biot
    Laboratoire de Catalyse de Lille UMR CNRS 8010, ENSCL, Batiment C7, Université des Sciences et Technologies, 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...
  38. ncbi Quinoline-resistance reversing agents for the malaria parasite Plasmodium falciparum
    Donelly 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...
  39. ncbi Extracellular lipid droplets promote hemozoin crystallization in the gut of the blood fluke Schistosoma mansoni
    Juliana 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...
  40. ncbi Pigment biocrystallization in Plasmodium falciparum
    Ernst Hempelmann
    Trends Parasitol 18:11. 2002
  41. pmc Differential effects of quinoline antimalarials on endocytosis in Plasmodium falciparum
    Lindi 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...
  42. ncbi Haemozoin: from melatonin pigment to drug target, diagnostic tool, and immune modulator
    Thomas 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...
  43. ncbi Porcine small intestine submucosa for soft tissue augmentation
    Jeffrey 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...
  44. ncbi Four aspartic proteases occur in the Plasmodium falciparum food vacuole
    Timothy J Egan
    Trends Parasitol 18:150. 2002