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Selected Publications 2014-2018

  1. Woodland, J.; Hunter, R.; Smith, P. J.; Egan, T. J.
    Chemical proteomics and super-resolution imaging reveal that chloroquine interacts with Plasmodium falciparum multidrug resistance-associated protein and lipids.
    ACS Chem. Biol. 2018, DOI: 10.1021/acschembio.8b00583.
  2. Joshi, M. C.; Okombo, J.; Nsumiwa, S.; Ndove, J.; Taylor, D.; Wiesner, L.; Hunter, R.; Chibale, K.; Egan, T. J.
    4 Aminoquinoline antimalarials containing a benzylmethylpyridylmethylamine group are active against drug resistant Plasmodium falciparum and exhibit oral activity in mice.
    J. Med. Chem. 2017, 60, 10245-10256.
  3. Vanaerschot, M.; Lucatoni, L.; Li, T.; Combrinck, J. M.; Ruecker, A.; Tiruppadiripuliyur, S. K.; Rubiano, K.; Ferreira, P. E.; Siciliano, G.; Gulati, S.; Henrich, P. P.; Ng, C. L.; Murithi, J. M.; Corey, V. C.; Duffy, S.; Lieberman, O. J.; Sinden, R. E.; Alano, P.; Delves, M. J.; Sim, K. L.; Winzeler, E. A.; Egan, T. J.; Hoffman, S. L.; Avery, V. M.; Fidock, D. A.
    Identifying hexahydroquinolines as new antimalarial candidates with potent blood stage and transmission-blocking activity.
    Nature Microbiol. 2017, 2, 1403-1414.
  4. Woodland, J.; Hunter, R.; Smith, P. J.; Egan, T. J.
    Shining new light on ancient drugs: preparation and subcellular localisation of novel fluorescent analogues of Cinchona alkaloids in intraerythrocytic Plasmodium falciparum.
    Org. Biomol. Chem. 2017, 15, 589-597.
  5. Wicht, K. J.; Combrinck, J. M.; Smith, P. J.; Hunter, R.; Egan, T. J.
    Identification and SAR Evaluation of Hemozoin-Inhibiting Benzamides Active against Plasmodium falciparum.
    J. Med. Chem. 2016, 59, 6512-6530.
  6. Kuter, D.; Streltsov, V.; Davydova, N.; Venter, G.A.; Naidoo, K.J.; Egan,T.J.
    Solution structures of chloroquine–ferriheme complexes modeled using MD simulation and investigated by EXAFS spectroscopy.
    J. Inorg. Biochem. 2016, 154, 114-125.
  7. Kuter, D.; Streltsov, V.; Davydova, N.; Venter, G. A.; Naidoo, K. J.; Egan, T. J.
    Molecular structures and solvation of free monomeric and dimeric ferriheme in aqueous solution: insights from molecular dynamics simulations and extended X-ray absorption fine structure spectroscopy.
    Inorg. Chem. 2014, 53, 10811-10824.
  8. Sandlin, R. D.; Fong, K. Y.; Wicht, K. J.; Carrell, H. M.; Egan, T. J.; Wright, D. W.
    Identification of β-hematin inhibitors in a high-throughput screening effort reveals scaffolds with in vitro antimalarial activity.
    Int. J. Parasitol. Drugs Drug Resist. 2014, 4, 316-325.
  9. Wicht, K. J.; Combrinck, J. M.; Smith, P. J.; Egan, T. J.
    Bayesian models trained with HTS data for predicting β-haematin inhibition and in vitro antimalarial activity.
    Bioorg Med Chem 2015, 23, 5210-5217.
  10. Combrinck, J.M.; Fong, K.Y.; Gibhard, L.; Smith, P.J.; Wright, D.W.; Egan, T.J.
    Optimization of a multi-well colorimetric assay to determine haem species in Plasmodium falciparum in the presence of anti-malarials.
    Malaria J. 2015, 14, e253.

Selected Prior Publications

  1. Egan, T. J.; Ross, D. C.; Adams, P. A. Quinoline anti-malarial drugs inhibit spontaneous formation of β-haematin (malaria pigment). FEBS Lett. 1994, 352, 54-57.
  2. Egan, T. J.; Mavuso, W. W.; Ross, D. C.; Marques, H. M. Thermodynamic factors controlling the interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX. J. Inorg. Biochem. 1997, 68, 137-145.
  3. Egan, T. J.; Hunter, R.; Kaschula, C. H.; Marques, H. M.; Misplon, A.; Walden, J. Structure-function relationships in aminoquinolines: effect of amino and chloro groups on quinoline-hematin complex formation, inhibition of β-hematin formation, and antiplasmodial activity. J. Med. Chem. 2000, 43, 283-291.
  4. Egan, T. J.; Mavuso, W. W.; Ncokazi, K. K. The mechanism of β-hematin formation in acetate solution. Parallels between hemozoin formation and biomineralization processes. Biochemistry 2001, 40, 204-213.
  5. Egan, T. J.; Combrinck, J. M.; Egan, J.; Hearne, G. R.; Marques, H. M.; Ntenteni, S.; Sewell, B.T.; Smith, P. J.; Taylor, D.; Van Schalkwyk, D. A.; Walden, J. C. Fate of haem iron in the malaria parasite Plasmodium falciparum. Biochem. J. 2002, 365, 343-347.
  6. Kaschula, C. H.; Egan, T. J.; Hunter, R.; Basilico, N.; Parapini, S.; Taramelli, D.; Pasini, E.; Monti, D. Structure-activity relationships in 4-aminoquinoline antiplasmodials. The role of the group at the 7-position. J. Med. Chem. 2002, 45, 3531-3539.
  7. Ncokazi, K. K.; Egan, T. J. A colorimetric high-throughput β-hematin inhibition screening assay for use in the search for antimalarial compounds. Anal. Biochem. 2005, 338, 306-319.
  8. Egan, T. J.; Chen, J. Y.-J.; de Villiers, K. A.; Mabotha, T. E.; Naidoo, K. J.; Ncokazi, K. K.; Langford, S. J.; McNaughton, D.; Pandiancherri, S.; Wood, B. R. Haemozoin (β-haematin) biomineralization occurs by self-assembly near the lipid/water interface. FEBS Lett. 2006, 580, 5105-5110.
  9. de Villiers, K. A.; Kaschula, C. H.; Egan, T. J.; Marques, H. M. Speciation and structure of ferriprotoporphyrin IX in aqueous solution: spectroscopic and diffusion measurements demonstrate dimerization, but not u-oxo dimer formation. J. Biol. Inorg. Chem. 2007, 12, 101-117.
  10. de Villiers, K. A.; Marques, H. M.; Egan, T. J. The crystal structure of halofantrine-ferriprotoporphyrin IX and the mechanism of action of arylmethanol antimalarials. J. Inorg. Biochem. 2008, 102, 1660-1667.
  11. Hoang, A.N.; Ncokazi, K.K; de Villiers, K.A.; Wright, D.W. and Egan, T.J. Crystallization of synthetic haemozoin (β-haematin) nucleated at the surface of lipid particles. Dalton Trans. 2010, 39, 1235-1244.
  12. Zishiri, V. K.; Joshi, M. C.; Hunter, R.; Chibale, K.; Smith, P. J.; Summers, R. L.; Martin, R. E.; Egan, T. J. 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). J. Med. Chem. 2011, 54, 6956-6968.
  13. Kuter, D.; Venter, G. A.; Naidoo, K. J.; Egan, T. J. Experimental and time-dependent density functional theory characterization of the UV-visible spectra of monomeric and μ-oxo dimeric ferriprotoporphyrin IX. Inorg. Chem. 2012, 51, 10233-10250.
  14. Gildenhuys, J.; le Roex, T.; Egan, T. J.; de Villiers, K. A. The single crystal X-ray structure of β-hematin DMSO solvate grown in the presence of chloroquine, a β-hematin growth-rate inhibitor. J. Am. Chem. Soc. 2013, 135, 1037-1047.
  15. Combrinck, J. M.; Mabotha, T. E.; Ncokazi, K. K.; Ambele, M. A.; Taylor, D.; Smith, P. J.; Hoppe, H. C.; Egan, T. J. Insights into the role of heme in the mechanism of action of antimalarials. ACS Chem. Biol. 2013, 8, 133-137.

Full List of Journal Articles

128. Woodland, J.; Hunter, R.; Smith, P. J.; Egan, T. J. Chemical proteomics and super-resolution imaging reveal that chloroquine interacts with Plasmodium falciparum multidrug resistance-associated protein and lipids. ACS Chem. Biol. 2018, DOI: 10.1021/acschembio.8b00583.

127. L'abbate, F. P.; Müller, R.; Openshaw, R.; Combrinck, J. M.; de Villiers, K. A.; Hunter, R.; Egan, T. J. Hemozoin inhibiting 2-phenylbenzimidazoles active against malaria parasites. Eur. J. Med. Chem. 2018, 159, 243-254.

126. Dare, N. A.; Egan, T. J. Heterogeneous catalysis with encapsulated haem and other synthetic porphyrins: Harnessing the power of porphyrins for oxidation reactions. Open Chem. 2018, 16, 763-789.

125. Dare, N. A.; Brammer, L.; Bourne, S. A.; Egan, T. J. Fe(III) protoporphyrin IX encapsulated in a zinc metal–organic framework shows dramatically enhanced peroxidatic activity. Inorg. Chem. 2018, 57, 1171-1183.

124. Mosaddeque, F.; Mizukami, S.; Kamel, M. G.; Teklemichael, A. A.; Dat, T. V.; Mizuta, S.; Toan, D. V.; Ahmed, A. M.; Vuong, N. L.; Elhady, M. T.; Giang, H. T. N.; Dang, T. N.; Fukuda, M.; Huyn, L. K.; Tanaka, Y.; Egan, T. J.; Kaneko, O.; Huy, N. T.; Hirayama, K. Prediction model for anti-malarial activities of hemozoin inhibitors using physicochemical properties. Antimicr. Agents Chemother. 2018, 62, e02424-17.

123. Joshi, M. C.; Okombo, J.; Nsumiwa, S.; Ndove, J.; Taylor, D.; Wiesner, L.; Hunter, R.; Chibale, K.; Egan, T. J. 4 Aminoquinoline antimalarials containing a benzylmethylpyridylmethylamine group are active against drug resistant Plasmodium falciparum and exhibit oral activity in mice J. Med. Chem. 2017, 60, 10245-10256.

122. Dinghra, S. K.; Redhi, D.; Combrinck, J. M.; Yeo, T.; Okombo, J.; Henrich, P. P.; Cowell, A. N.; Gupta, P.; Stegman, M. L.; Hoke, J. M.; Cooper, R. A.; Winzeler, E.; Mok, S.; Egan, T. J.; Fidock, D. A. A variant PfCRT isoform can contribute to Plasmodium falciparum resistance to the first-line partner drug piperaquine. mBio 2017, 8, e00303-17.

121. Vanaerschot, M.; Lucatoni, L.; Li, T.; Combrinck, J. M.; Ruecker, A.; Tiruppadiripuliyur, S. K.; Rubiano, K.; Ferreira, P. E.; Siciliano, G.; Gulati, S.; Henrich, P. P.; Ng, C. L.; Murithi, J. M.; Corey, V. C.; Duffy, S.; Lieberman, O. J.; Sinden, R. E.; Alano, P.; Delves, M. J.; Sim, K. L.; Winzeler, E. A.; Egan, T. J.; Hoffman, S. L.; Avery, V. M.; Fidock, D. A. Identifying hexahydroquinolines as new antimalarial candidates with potent blood stage and transmission-blocking activity. Nature Microbiol. 2017, 2, 1403-1414.

120. Okombo, J.; Singh, K.; Mayoka, G.; Ndubi, F.; Barnard, L.; Njogu, P. M.; Njoroge, M.; Gibhard, L.; Brunschwig, C.; Vargas, M.; Keiser, J.; Egan, T. J.; Chibale, K. Antischistosomal activity of pyrido [1, 2-a] benzimidazole derivatives and correlation with inhibition of β-hematin formation. ACS Infect. Dis. 2017, 3, 411-420.

119. Singh, K.; Okombo, J.; Brunschwig, C.; Ndubi, F.; Barnard, L.; Wilkinson, C.; Njogu, P. M.; Njoroge, M.; Laing, L.; Machado, M.; Prudêncio, M.; Reader, J.; Botha, M.; Nondaba, S.; Birkholtz, L.-M.; Lauterbach, S.; Churchyard, A.; Coetzer, T. L.; Burrows, J. N.; Yeates, C.; Denti, P.; Wiesner, L.; Egan, T. J.; Wittlin, S.; Chibale, K. Antimalarial pyrido[1,2-a]benzimidazoles: Lead optimization, parasite life cycle stage profile, mechanistic evaluation, killing kinetics, and in vivo oral efficacy in a mouse model. J. Med. Chem. 2017, 60, 1432-1448.

118. Wicht, K. J.; Combrinck, J. M.; Smith, P. J.; Hunter, R.; Egan, T. J. Identification and mechanistic evaluation of hemozoin-inhibiting triarylimidazoles active against Plasmodium falciparum. ACS Med. Chem. Lett. 2017, 8, 201-205.

117. Woodland, J. G.; Hunter, R.; Smith, P. J.; Egan, T. J. Shining new light on ancient drugs: Preparation and subcellular localisation of novel fluorescent analogues of Cinchona alkaloids in intraerythrocytic Plasmodium falciparu. Org. Biomol. Chem. 2017, 15, 589-597.

116. Stringer, T.; de Kock, C.; Guzgay, H.; Okombo, J.; Liu, J.; Kanetake, S.; Kim, J.; Tam, C.; Cheng, L. W.; Smith, P. J.; Hendricks, D. T.; Land, K. M.; Egan, T. J.; Smith, G. S. Mono- and multimeric ferrocene congeners of quinoline-based polyamines as potential antiparasitics. Dalton Trans 2016, 45, 13415-13426.

115. Gabryszewski, S.; Dhingra, S. K.; Combrinck, J. M.; Lewis, I. A.; Callaghan, P. S.; Hassett, M. R.; Siriwardana, A.; Henrich, P. P.; Lee, A. H.; Gnädig, N. F.; Musset, L.; Llinás, M.; Egan, T. J.; Roepe, P. D.; Fidock, D. A. Evolution of fitness cost-neutral mutant PfCRT conferring P. falciparum 4-aminoquinoline drug resistance is accompanied by altered parasite metabolism and digestive vacuole physiology. PLoS Pathog. 2016, 12, e1005976

114. Wicht, K. J.; Combrinck, J. M.; Smith, P. J.; Hunter, R.; Egan, T. J. Identification and SAR Evaluation of Hemozoin-Inhibiting Benzamides Active against Plasmodium falciparum. J. Med. Chem. 2016, 59, 6512-6530.

113. Kuter, D; Mohunlal, R; Fitzroy, S-M; Asher, C; Smith, P.J.; Egan, T.J.; de Villiers, K.A. Insights into the initial stages of lipid-mediated haemozoin nucleation. Cryst. Eng. Comm. 2016, 18, 5177-5187

112. Kuter, D.; Streltsov, V.; Davydova, N.; Venter, G.A.; Naidoo, K.J.; Egan,T.J. Solution structures of chloroquine–ferriheme complexes modeled using MD simulation and investigated by EXAFS spectroscopy. J. Inorg. Biochem. 2016, 154, 114-125.

111. Dambuza, N.S.; Smith, P.J.; Evans, A.; Norman, J.; Taylor, D.; Andayi, A.; Egan, T.J.; Chibale, K.; Wiesner, L. Antiplasmodial activity, in vivo pharmacokinetics and anti-malarial efficacy evaluation of hydroxypyridinone hybrids in a mouse model. Malaria J. 2015, 14, e505.

110. Stringer, T.; Taylor, D.; Guzgay, H.; Shokar, A.; Au, A.; Smith, P.J.; Hendricks, D.T.; Land, K.M.; Egan, T.J.; Smith, G.S. Polyamine quinoline rhodium complexes: synthesis and pharmacological evaluation as antiparasitic agents against Plasmodium falciparum and Trichomonas vaginalis. Dalton Trans 2015, 44, 14906-14917.

109. Ongarora, D. S. B.; Strydom, N.; Wicht, K.; Njoroge, M.; Wiesner, L.; Egan, T.J.; Wittlin, S.; Jurva, U.; Masimirembwa, C. M.; Chibale, K. Antimalarial benzoheterocyclic 4-aminoquinolines: Structure–activity relationship, in vivo evaluation, mechanistic and bioactivation studies. Bioorg. Med. Chem. 2015, 23, 5419-5432.

108. Stringer, T.; Guzgay, H.; Combrinck, J.M.; Hopper, M.; Hendricks, D.T.; Smith, P.J.; Land, K.M.; Egan, T.J.; Smith, G.S. Synthesis, characterization and pharmacological evaluation of ferrocenyl azines and their rhodium(I) complexes. J. Organomet. Chem. 2015, 788, 1-8.

107. Verlinden, B.K.; de Beer, M.; Pachaiyappan, B.; Besaans, E.; Andayi, W.A.; Reader, J.; Niemand, J.; van Biljon, R.; Guy, K.; Egan, T.; Woster, P.M.; Birkholtz, L.-M. Interrogating alkyl and arylalkylpolyamino (bis)urea and (bis)thiourea isosteres as potent antimalarial chemotypes against multiple lifecycle forms of Plasmodium falciparum parasites. Bioorg. Med. Chem. 2015, 23, 5131-5143.

106. Combrinck, J.M.; Fong, K.Y.; Gibhard, L.; Smith, P.J.; Wright, D.W.; Egan, T.J. Optimization of a multi-well colorimetric assay to determine haem species in Plasmodium falciparum in the presence of anti-malarials. Malaria J. 2015, 14, e253.

105. Figueiras, M.; Coelho, L; Wicht, K.J.; Santos, S.A; Lavrado, J.; Gut, J.; Rosenthal, P.J.; Nogueira, F.; Egan, T.J; Moreira, R.; Paulo, A. N10,N11-di-alkylamine indolo[3,2-b]quinolines as hemozoin inhibitors: Design, synthesis and antiplasmodial activity. Bioorg. Med. Chem. 2015, 23, 1530-1539.

104. Wicht, K. J.; Combrinck, J. M.; Smith, P. J.; Egan, T. J. Bayesian models trained with HTS data for predicting β-haematin inhibition and in vitro antimalarial activity. Bioorg. Med. Chem. 2015, 23, 5210-5217.

103. Corbett, Y.; Parapini, S.; D'Alessandro, S.; Scaccabarozzi, D.; Rocha, B.C.; Egan, T.J.; Omar, A.; Galastri, L.; Fitzgerald, K.A.; Golenbock, D.T.; Taramelli, D.; Basilico, N. Involvement of Nod2 in the innate immune response elicited by malarial pigment hemozoin. Micobes Infect. 2015, 17, 184-194.

102. Chugh, M.; Scheurer, C.; Sax, S.; Bilsland, E.; van Schalkwyk, D. A.; Wicht, K. J.; Hofmann, N.; Sharma, A.; Bashyam, S.; Singh, S.; Oliver, S. G.; Egan, T. J.; Malhotra, P.; Sutherland, C. J.; Beck, H.-P.; Wittlin, S.; Spangenberg, T.; Ding, X. C. Identification and deconvolution of cross-resistance signals from antimalarial compounds using multidrug-resistant Plasmodium falciparum strains. Antimicr. Agents Chemother. 2015, 59, 1110-1118.

101. Wang, N.; Wicht, K. J.; Shaban, E.; Ngoc, T. A.; Wang, M.-Q.; Hayashi, I.; Hossain, M. I.; Takemasa, Y.; Kaiser, M.; El Sayed, I. E.; Egan, T. J.; Inokuchi, T. Synthesis and evaluation of artesunate-indoloquinoline hybrids as antimalarial drug candidates. MedChemComm 2014, 5, 927-931.

100. Wang, N.; Wicht, K. J.; Imai, K.; Wang, M.-Q.; Ngoc, T. A.; Kiguchi, R.; Kaiser, M.; Egan, T. J.; Inokuchi, T. Synthesis, β-haematin inhibition, and in vitro antimalarial testing of isocryptolepine analogues: SAR study of indolo[3,2-c]quinolines with various substituents at C2, C6, and N11. Bioorg. Med. Chem. 2014, 22, 2629-2642.

99. Stiebler, R.; Majerowicz, D.; Knudsen, J.; Gondim, K. C.; Wright, D. W.; Egan, T. J.; Oliveira, M. F. Unsaturated glycerophospholipids mediate heme crystallization: biological implications for hemozoin formation in the kissing bug Rhodnius prolixus. PLoS One 2014, 9, e88976.

98. Shaban, E.; Wicht, K. J.; Wang, N.; Mei, Z.-W.; Hayashi, I.; El Gokha, A. A. A.; Kaiser, M.; El Sayed, I. E. T.; Egan, T. J.; Inokuchi, T. Synthesis and antimalarial activity of some neocryptolepine analogues carrying a multifunctional linear and branched carbon-side chain. Heterocycles 2014, 89, 1055-1064.

97. Sandlin, R. D.; Fong, K. Y.; Wicht, K. J.; Carrell, H. M.; Egan, T. J.; Wright, D. W. Indentification of β-hematin inhibitors in a high-throughput screening effort reveals scaffolds with in vitro antimalarial activity. Int. J. Parasitol. Drugs Drug Resist. 2014, 4, 316-325.

96. Raj, R.; Mehra, V.; Gut, J.; Rosenthal, P. J.; Wicht, K. J.; Egan, T. J.; Hopper, M.; Wrischnik, L. A.; Land, K. M.; Kumar, V. Discovery of highly selective 7-chloroquinoline-thiohydantoins with potent antimalarial activity. Eur. J. Med. Chem. 2014, 84, 425-432.

95. Kuter, D.; Streltsov, V.; Davydova, N.; Venter, G. A.; Naidoo, K. J.; Egan, T. J. Molecular structures and solvation of free monomeric and dimeric ferriheme in aqueous solution: insights from molecular dynamics simulations and extended X-ray absorption fine structure spectroscopy. Inorg. Chem. 2014, 53, 10811-10824.

94. Kuter, D.; Benjamin, S. J.; Egan, T. J. Multiple spectroscopic and magnetic techniques show that chloroquine induces formation of the μ-oxo dimer of ferriprotoporphyrin IX. J. Inorg. Biochem. 2014, 133, 40-49.

93. Andayi, W. A.; Egan, T. J.; Chibale, K. Kojic acid derived hydroxypyridinone-chloroquine hybrids: Synthesis, crystal structure, antiplasmodial activity and β-haematin inhibition. Bioorg. Med. Chem. Lett. 2014, 24, 3263-3267.

92. Wang, N.; Wicht, K. J.; Wang, L.; Lu, W.-J.; Misumi, R.; Wang, M.-q.; El Gokha, A. A. A.; Kaiser, M.; El Sayed, I.; Egan, T. J.; Inokuchi, T. Synthesis and in vitro testing of antimalarial activity of non-natural type neocryptolepines: structure-activity relationship study of 2,11- and 9,11-disubstituted 6-methylindolo[2,3-b]quinolines. Chem. Pharm. Bull. 2013, 61, 1282-1290.

91. Stringer, T.; Taylor, D.; de Kock, C.; Guzgay, H.; Au, A.; An, S. H.; Sanchez, B.; O’Connor, R.; Pate, N.; Land, K. M.; Smith, P. J.; Hendricks, D. T.; Egan, T. J.; Smith, G. S. Synthesis, characterization, antiparasitic and cytotoxic evaluation of thioureas conjugated to polyamine scaffolds. Eur. J. Med. Chem. 2013, 69, 90-98.

90. Nsumiwa, S.; Kuter, D.; Wittlin, S.; Chibale, K.; Egan, T. J. Structure–activity relationships for ferriprotoporphyrin IX association and β-hematin inhibition by 4-aminoquinolines using experimental and ab initio methods. Bioorg. Med. Chem. 2013, 21, 3738-3748.

89. Lu, W.-J.; Wicht, K. J.; Wang, L.; Imai, K.; Mei, Z.-W.; Kaiser, M.; El Sayed, I.; Egan, T. J.; Inokuchi, T. Synthesis and antimalarial testing of neocryptolepine analogues: Addition of ester function in SAR study of 2,11-disubstituted indolo [2,3-b]quinolines. Eur. J. Med. Chem. 2013, 64, 498-511.

88. Joshi, M. C.; Wicht, K. J.; Taylor, D.; Hunter, R.; Smith, P. J.; Egan, T. J. In vitro antimalarial activity, β-haematin inhibition and structure-activity relationships in a series of quinoline triazoles. Eur. J. Med. Chem. 2013, 69, 338-347.

87. Gildenhuys, J.; le Roex, T.; Egan, T. J.; de Villiers, K. A. The single crystal X-ray structure of β-hematin DMSO solvate grown in the presence of chloroquine, a β-hematin growth-rate inhibitor. J. Am. Chem. Soc. 2013, 135, 1037-1047.

86. Egan, T. J.; Kuter, D. Dual-functioning antimalarials that inhibit the chloroquine-resistance transporter. Future Microbiol. 2013, 8, 475-489.

85. Combrinck, J. M.; Mabotha, T. E.; Ncokazi, K. K.; Ambele, M. A.; Taylor, D.; Smith, P. J.; Hoppe, H. C.; Egan, T. J. Insights into the role of heme in the mechanism of action of antimalarials. ACS Chem. Biol. 2013, 8, 133-137.

84. Andayi, W. A.; Egan, T. J.; Gut, J.; Rosenthal, P. J.; Chibale, K. Synthesis, antiplasmodial activity, and β-hematin inhibition of hydroxypyridone–chloroquine hybrids. ACS Med. Chem. Lett. 2013, 4, 642-646.

83. Ambele, M. A.; Sewell, B. T.; Cummings, F. R.; Smith, P. J.; Egan, T. J. Synthetic hemozoin (β-hematin) crystals nucleate at the surface of neutral lipid droplets that control their sizes. Cryst. Growth Des. 2013, 13, 4442-4452.

82. Kuter, D.; Venter, G. A.; Naidoo, K. J.; Egan, T. J. Experimental and time-dependent density functional theory characterization of the UV−visible spectra of monomeric and μ-oxo dimeric ferriprotoporphyrin IX. Inorg. Chem. 2012, 51, 10233-10250.

81. Ambele, M. A.; Egan, T. J. Neutral lipids associated with haemozoin mediate efficient and rapid β-haematin formation at physiological pH, temperature and ionic composition. Malar. J. 2012, 11, 337.

80. Zishiri, V. K.; Joshi, M. C.; Hunter, R.; Chibale, K.; Smith, P. J.; Summers, R. L.; Martin, R. E.; Egan, T. J. 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). J. Med. Chem. 2011, 54, 6956-6968.

79. Zishiri, V. K.; Hunter, R.; Smith, P. J.; Taylor, D.; Summers, G.; Kirk, K.; Martin, R. E.; Egan, T. J. A series of structurally simple chloroquine chemosensitizing dibemethin derivatives that inhibit chloroquine transport by PfCRT. Eur. J. Med. Chem. 2011, 46, 1729-1742.

78. Kuter, D.; Chibale, K.; Egan, T. J. Linear free energy relationships predict coordination and π-stacking interactions of small molecules with ferriprotoporphyrin IX. J. Inorg. Biochem. 2011, 105, 684-692.

77. Guantai, E. M.; Ncokazi, K. K.; Egan, T. J.; Gut, J.; Rosenthal, P. J.; Bhampidipati, R.; Kopinathan, A.; Smith, P. J.; Chibale, K. Enone- and chalcone-chloroquine hybrid analogues: in silico guided design, synthesis, antiplasmodial activity, in vitro metabolism, and mechanistic studies. J. Med. Chem. 2011, 54, 3637-3649.

76. Dubar, F.; Egan, T. J.; Pradines, B.; Kuter, D.; Ncokazi, K. K.; Forge, D.; Paul, J.-F.; Pierrot, C.; Kalamou, H.; Khalife, J.; Buisine, E.; Rogier, C.; Vezin, H.; Forfar, I.; Slomianny, C.; Trivelli, X.; Kapishnikov, S.; Leiserowitz, L.; Dive, D.; Biot, C. The antimalarial ferroquine: role of the metal and intramolecular hydrogen bond in activity and resistance. ACS Chem. Biol. 2011, 6, 275-287.

75. Feng, T. S.; Guantai, E. M.; Nell, M.; van Rensburg, C. E. J.; Ncokazi, K. K.; Egan, T. J.; Hoppe, H. C.; Chibale, K. Effects of highly active novel artemisinin-chloroquinoline hybrid compounds on β-hematin formation, parasite morphology and endocytosis in Plasmodium falciparum. Biochem. Pharmacol. 2011, 82, 236-247.

74. Guantai, E. M.; Ncokazi, K. K.; Egan, T. J.; Gut, J.; Rosenthal, P. J.; Smith, P. J.; Chibale, K. Design, synthesis and in vitro antimalarial evaluation of triazole-linked chalcone and dienone hybrid compounds. Bioorg. Med. Chem. 2010, 18, 8243-8256.

73. Hoang, A. N.; Ncokazi, K. K.; de Villiers, K. A.; Wright, D. W.; Egan, T. J. Crystallization of synthetic haemozoin (β-haematin) nucleated at the surface of lipid particles. Dalton Trans. 2010, 39, 1235-1244.

72. Hoang, A. N.; Sandlin, R. D.; Omar, A.; Egan, T. J.; Wright, D. W. The neutral lipid composition present in the digestive vacuole of Plasmodium falciparum concentrates heme and mediates β-hematin formation with an unusually low activation energy. Biochemistry 2010, 49, 10107-10116.

71. Stiebler, R.; Hoang, A. N.; Egan, T. J.; Wright, D. W.; Oliveira, M. F. Increase on the initial soluble heme levels in acidic conditions is an important mechanism for spontaneous heme crystallization in vitro. PloS ONE 2010, 5, e12694.

70. Stiebler, R.; Timm, B. L.; Oliveira, P. L.; Hearne, G. R.; Egan, T. J.; Oliveira, M. F. On the physico-chemical and physiological requirements of hemozoin formation promoted by perimicrovillar membranes in Rhodnius prolixus midgut. Insect Biochem. Mol. Biol. 2010, 40, 284-292.

69. Macedo, B.; Kaschula, C. H.; Hunter, R.; Chaves, J. A. P.; van der Merwe, J. D.; Silva, J. L.; Egan, T. J.; Cordeiro, Y. Synthesis and anti-prion activity evaluation of aminoquinoline analogues. Eur. J. Med. Chem. 2010, 45, 5468-5473.

68. Asher, C.; de Villiers, K. A.; Egan, T. J. Speciation of ferriprotoporphyrin IX in aqueous and mixed aqueous solution is controlled by solvent identity, pH, and salt concentration. Inorg. Chem. 2009, 48, 7994-8003.

67. Corrêa Soares, J. B.; Menezes, D.; Vannier-Santos, M. A.; Ferreira-Pereira, A.; Almeida, G. T.; Venancio, T. M.; Verjovski-Almeida, S.; Zishiri, V. K.; Kuter, D.; Hunter, R.; Egan, T. J.; Oliveira, M. F. Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols. PloS Negl. Trop. Dis. 2009, 14, e477.

66. de Villiers, K. A.; Osipova, M.; Mabotha, T. E.; Solomonov, I.; Feldman, Y.; Kjaer, K.; Weissbuch, I.; Egan, T. J.; Leiserowitz, L. Oriented nucleation of β-hematin crystals induced at various interfaces: relevance to hemozoin formation. Cryst. Growth Des. 2009, 9, 626-632.

65. Webster, G. T.; de Villiers, K. A.; Egan, T. J.; Deed, S.; Tilley, L.; Tobin, M. J.; Bambery, K. R.; McNaughton, D.; Wood, B. R. Discriminating the intraerythrocytic lifecycle stages of the malaria parasite using synchrotron FT-IR microspectroscopy and artificial neural network. Anal. Chem. 2009, 81, 2516-2524.

64. de Villiers, K. A.; Egan, T. J. Recent advances in the discovery of haem targeting drugs for malaria and schistosomiasis. Molecules 2009, 14, 2868-2887.

63. de Villiers, K. A.; Marques, H. M.; Egan, T. J. The crystal structure of halofantrine-ferriprotoporphyrin IX and the mechanism of action of arylmethanol antimalarials. J. Inorg. Biochem. 2008, 102, 1660-1667.

62. Egan, T. J. Recent advances in understanding the mechanism of hemozoin (malaria pigment) formation. J. Inorg. Biochem. 2008, 102, 1288-1299.

61. Egan, T. J. Haemozoin formation. Mol. Biochem. Parasitol. 2008, 157, 127-136.

60. October, N.; Watermeyer, N. D.; Yardley, V.; Egan, T. J.; Ncokazi, K. K.; Chibale, K. Reversed chloroquines based on the 3,4-dihydropyrimidin-2(1H)-one scaffold: synthesis and evaluation for antimalarial, beta-haematin inhibition, and cytotoxic activity. ChemMedChem 2008, 3, 1649-1653.

59. Roberts, L.; Egan, T. J.; Joiner, K.; Hoppe, H. C. Differential effects of quinoline antimalarials on endocytosis in Plasmodium falciparum. Antimicr. Agents Chemother. 2008, 52, 1840-1842.

58. Musonda, C. C.; Yardley, V.; Carvalho de Souza, R. C.; Ncokazi, K. K.; Egan, T. J.; Chibale, K. Antiplasmodial, β-haematin inhibition, antitrypanosomal and cytotoxic activity in vitro of novel 4-aminoquinoline 2-imidazolines. Org. Biomol. Chem. 2008, 6, 4446-4451.

57. Corrêa Soares, J. B. R.; Lara, F. A.; Cunha, P. R. B. B.; Atella, G. C.; Maya-Monteiro, C. M.; d’Avila, J. C. P.; Menezes, D.; Vannier-Santos, M.; Oliveira, P. L.; Egan, T. J.; Oliveira, M. F. Extracellular lipid droplets promote hemozoin crystallization in the gut of the blood fluke Schistosoma mansoni. FEBS Lett. 2007, 581, 1742-1750.

56. Egan, T. J.; Kaschula, C. H. Strategies to reverse drug resistance in malaria. Curr. Opin. Infect. Dis. 2007, 20, 598-604.

55. Hänscheid, T.; Egan, T. J.; Grobusch, M. P. Haemozoin: from melatonin pigment to drug target, diagnostic tool, and immune modulator. Lancet Infect. Dis. 2007, 7, 675-685.

54. de Villiers, K. A.; Kaschula, C. H.; Egan, T. J.; Marques, H. M. Speciation and structure of ferriprotoporphyrin IX in aqueous solution: spectroscopic and diffusion measurements demonstrate dimerization, but not μ-oxo dimer formation. J. Biol. Inorg. Chem. 2007, 12, 101-117.

53. Bourne, S. A.; de Villiers, K. A.; Egan, T. J. Three 4-aminoquinolines of antimalarial interest. Acta Cryst. 2006, C62, o53-o57.

52. Buisine, E.; de Villiers, K. A.; Egan, T. J.; Biot, C. Solvent-induced effects: self-association of positively charged π systems. J. Am. Chem. Soc. 2006, 128, 12122-12128.

51. Egan, T. J. Interactions of quinoline antimalarials with hematin in aqueous solution. J. Inorg. Biochem. 2006, 100, 916-926.

50. Egan, T. J. Chloroquine and primaquine: combining old drugs as a new weapon against falciparum malaria? Trends Parasitol. 2006, 22, 235-237.

49. Egan, T. J.; Tshivhase, M. G. Kinetics of β-haematin formation from suspensions in aqueous benzoic acid. Dalton Trans. 2006, 5024-5032.

48. van Schalkwyk, D.; Egan, T. J. Quinoline-resistance reversing agents for the malaria parasite Plasmodium falciparum. Drug Resist. Update 2006, 9, 211-226.

47. Egan, T. J.; Chen, J. Y.-J.; de Villiers, K. A.; Mabotha, T. E.; Naidoo, K. J.; Ncokazi, K. K.; Langford, S. J.; McNaughton, D.; Pandiancherri, S.; Wood, B. R. Haemozoin (β-haematin) biomineralization occurs by self-assembly near the lipid/water interface. FEBS Lett. 2006, 580, 5105-5110.

46. Ncokazi, K. K.; Egan, T. J. A colorimetric high-throughput β-hematin inhibition screening assay for use in the search for antimalarial compounds. Anal. Biochem. 2005, 338, 306-319.

45. Egan, T. J.; Ncokazi, K. K. Quinoline antimalarials decrease the rate of β-hematin formation. J. Inorg. Biochem. 2005, 99, 1532-1539.

44. Biot, C.; Taramelli, D.; Forfar-Bares, I.; Maciejewski, L. A.; Boyce, M.; Nowogrocki, G.; Brocard, J. S.; Basilico, N.; Olliaro, P.; Egan, T. J. Insights into the mechanism of action of ferroquine. Relationship between physicochemical properties and antiplasmodial activity. Mol. Pharmaceut. 2005, 2, 185-193.

43. Egan, T. J. Haemozoin formation as a target for the rational design of new antimalarials. Drug Design Revs Online 2004, 1, 93-110.

42. Egan, T. J.; Ncokazi, K. K. Effects of solvent composition and ionic strength on the interaction of quinoline antimalarials with ferriprotoporphyrin IX. J. Inorg. Biochem. 2004, 98, 144-152.

41. Egan, T. J.; Rodgers, A. L.; Siele, T. Nucleation of calcium oxalate crystals on an imprinted polymer surface from pure aqueous solution and urine. J. Biol. Inorg. Chem. 2004, 9, 195-202.

40. Egan, T. J.; Koch, K. R.; Swan, P. L.; Clarkson, C.; Van Schalkwyk, D. A.; Smith, P. J. In vitro antimalarial activity of a series of cationic 2,2′-bipyridyl- and 1,10-phenanthrolineplatinum(II) benzoylthiourea complexes. J. Med. Chem. 2004, 47, 2926-2934.

39. Egan, T. J. Haemozoin (malaria pigment): a unique crystalline drug target. Drug Disc. Today Targets 2003, 2, 115-124.

38. Egan, T. J. Physico-chemical aspects of hemozoin (malaria pigment) structure and formation. J. Inorg. Biochem. 2002, 91, 19-26.

37. Egan, T. J. Haemozoin formation is the pathway of haem disposal in the malaria parasite Plasmodium falciparum. S. Afr. J. Sci. 2002, 98, 411-412.

36. Hempelmann, E.; Egan, T. J. Pigment biocrystallization in Plasmodium falciparum. Trends Parasitol. 2002, 18, 11.

35. Kaschula, C. H.; Egan, T. J.; Hunter, R.; Basilico, N.; Parapini, S.; Taramelli, D.; Pasini, E.; Monti, D. Structure-activity relationships in 4-aminoquinoline antiplasmodials. The role of the group at the 7-position. J. Med. Chem. 2002, 45, 3531-3539.

34. Egan, T. J.; Combrinck, J. M.; Egan, J.; Hearne, G. R.; Marques, H. M.; Ntenteni, S.; Sewell, B. T.; Smith, P. J.; Taylor, D.; van Schalkwyk, D. A.; Walden, J. C. Fate of haem iron in the malaria parasite Plasmodium falciparum. Biochem. J. 2002, 365, 343-347.

33. Egan, T. J. Quinoline antimalarials. Exp. Opin. Ther. Patents 2001, 11, 185-209.

32. Egan, T. J. Structure-function relationships in chloroquine and related 4-aminoquinoline antimalarials. Minirev. Med. Chem. 2001, 1, 114-124.

31. Marques, H. M.; Ngoma, B.; Egan, T. J.; Brown, K. L. Parameters for the AMBER force field for the molecular mechanics modeling of the cobalt corrinoids. J. Mol. Struct. 2001, 561, 71-91.

30. Egan, T. J.; Mavuso, W. W.; Ncokazi, K. K. The mechanism of β-hematin formation in acetate solution. Parallels between hemozoin formation and biomineralization processes. Biochemistry 2001, 40, 204-213.

29. Makgatho, M. E.; Anderson, R.; O’ Sullivan, J. F.; Egan, T. J.; Freese, J. A.; Cornelius, N.; van Rensburg, C. E. J. Tetramethylpiperidine-substituted phenazines as novel anti-plasmodial agents. Drug Dev. Res. 2000, 50, 195-202.

28. Parapini, S.; Basilico, N.; Pasini, E.; Egan, T. J.; Olliaro, P.; Taramelli, D.; Monti, D. Standardization of the physicochemical parameters to assess in vitro the β-hematin inhibitory activity of antimalarial drugs. Exp. Parasitol. 2000, 96, 249-256.

27. Egan, T. J.; Hunter, R.; Kaschula, C. H.; Marques, H. M.; Misplon, A.; Walden, J. C. Structure-function relationships in aminoquinolines: effect of amino and chloro groups on quinoline-hematin complex formation, inhibition of β-hematin formation, and antiplasmodial activity. J. Med. Chem. 2000, 43, 283-291.

26. Egan, T. J.; Hempelmann, E.; Mavuso, W. W. Characterisation of synthetic β-haematin and effects of the antimalarial drugs quinidine, halofantrine, desbutylhalofantrine and mefloquine on its formation. J. Inorg. Biochem. 1999, 73, 101-107.

25. Egan, T. J.; Marques, H. M. The role of haem in the activity of chloroquine and related antimalarial drugs. Coord. Chem. Rev. 1999, 190-192, 493-517.

24. Egan, T. J.; Hunter, R.; Kaschula, C. H.; Marques, H. M.; Mavuso, W. W. Towards the rational design of antimalarial drugs. S. Afr. J. Sci. 1998, 94, 277-278.

23. Egan, T. J.; Mavuso, W. W.; Ross, D. C.; Marques, H. M. Thermodynamic factors controlling the interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX. J. Inorg. Biochem. 1997, 68, 137-145.

22. Marques, H. M.; Shongwe, M. S.; Munro, O. Q.; Egan, T. J. The haempeptides from cytochrome c. Exploring the basic chemistry of the iron porphyrins and modelling aspects of the haemoproteins. S. Afr. J. Chem. 1997, 50, 166-180.

21. Adams, P. A.; Berman, P. A. M.; Egan, T. J.; Marsh, P. J.; Silver, J. The iron-environment in heme and heme-antimalarial complexes of pharmacological interest. J. Inorg. Biochem. 1996, 63, 69-77.

20. Marques, H. M.; Voster, K.; Egan, T. J. The interaction of the heme-octapeptide, N-acetylmicroperoxidase-8 with antimalarial drugs: solution studies and modeling by molecular mechanics methods. J. Inorg. Biochem. 1996, 64, 7-23.

19. Egan, T. J.; Ross, D. C.; Adams, P. A. The mechanism of action of quinolines and related anti-malarial drugs. S. Afr. J. Sci. 1996, 92, 11-14.

18. Adams, P. A.; Egan, T. J.; Ross, D. C.; Silver, J.; Marsh, P. J. The chemical mechanism of β-haematin formation studied by Mössbauer spectroscopy. Biochem. J. 1996, 318, 25-27.

17. Marques, H. M.; Walton, T.; Egan, T. J. Release of iron from C-terminal monoferric transferrin to phosphate and pyrophosphate at pH 5.5 proceeds through two pathways. J. Inorg. Biochem. 1995, 57, 11-21.

16. Ross, D. C.; Egan, T. J.; Purves, L. R. Periodate modification of human serum transferrin Fe(III)-binding sites. Inhibition of carbonate insertion into Fe(III)- and Cu(II)-chelator-transferrin ternary complexes. J. Biol. Chem. 1995, 270, 12404-12410.

15. Egan, T. J.; Baldwin, D. A.; Denner, L.; Levendis, D. C.; Marques, H. M. Guanidinium β-cis-(carbonato-O,O’)-(N,N’-ethylenediaminediacetato-N,N’,O,O”)-cobaltate(III). Acta Cryst. 1995, C51, 1994-1997.

14. Egan, T. J.; Ross, D. C.; Adams, P. A. Quinoline anti-malarial drugs inhibit spontaneous formation of β-haematin (malaria pigment). FEBS Lett. 1994, 352, 54-57.

13. Egan, T. J.; Ross, D. C.; Purves, L. R. Iron and the transferrins: mechanisms of iron binding and release. S. Afr. J. Sci. 1994, 90, 539-544.

12. Egan, T. J.; Zak, O.; Aisen, P. The anion requirement for iron release from transferrin is preserved in the receptor-transferrin complex. Biochemistry 1993, 32, 8162-8167.

11. Naidoo, D. P.; Egan, T. J.; Purves, L. R. Fibrin D-dimer as a zinc-potentiated substrate for a puff-adder venom protease. S. Afr. J. Sci. 1993, 89, 451-456.

10. Egan, T. J. Fluorescence energy transfer studies on fluoresceinated human serum transferrin. Identification of the possible fluoresceination sites. S. Afr. J. Sci. 1993, 89, 446-450.

9. Egan, T. J.; Barthakur, S. R.; Aisen, P. Catalysis of the Haber-Weiss reaction by iron-diethylenetriaminepenataacetate. J. Inorg. Biochem. 1992, 48, 241-249.

8. Egan, T. J.; Ross, D. C.; Purves, L. R.; Adams, P. A. Mechanism of iron release from human serum C-terminal monoferric transferrin to pyrophosphate: kinetic discrimination between alternative mechanisms. Inorg. Chem. 1992, 31, 1994-1998.

7. Marques, H. M.; Watson, D. L.; Egan, T. J. Kinetics of iron removal from human serum monoferric transferrins by citrate. Inorg. Chem. 1991, 30, 3758-3762.

6. Baldwin, D. A.; Egan, T. J.; Marques, H. M. The effects of anions on the kinetics of reductive elimination of iron from monoferrictransferrins by thiols. Biochim. Biophys. Acta 1990, 1038, 1-9.

5. Marques, H. M.; Egan, T. J.; Pattrick, G. The non-reductive removal of iron from human serum N-terminal monoferric transferrin by pyrophosphate. S. Afr. J. Sci. 1990, 86, 21-24.

4. Marques, H. M.; Egan, T. J.; Marsh, J. H.; Mellor, J. R.; Munro, O. Q. Nucleophilic participation of incoming ligands in the transition state of substitution reactions of aquocobalamin: kinetics of the reaction with imidazole and its derivatives. Inorg. Chim. Acta 1989, 166, 249-255.

3. Baldwin, D. A.; Egan, T. J. An inorganic perspective of human serum transferrin. S. Afr. J. Sci. 1987, 83, 22-31.

2. Baldwin, D. A.; Egan, T. J.; von Wandruszka, R. M. A. Fluorescence studies on human serum transferrin. S. Afr. J. Chem. 1986, 39, 197-200.

1. Baldwin, D. A.; Denner, L.; Egan, T. J.; Markwell, A. J. Structure of guanidinium bicarbonate: a model for the bicarbonate anion binding site of the transferrins. Acta Cryst. 1986, C42, 1197-1199.

 

Book Chapters

3. de Villiers K.A. and Egan T.J. (2014). Iron(III) protoporphyrin IX and hemozoin: key targets in the chemotherapy of malaria. Handbook of Porphyrin Science, Vol. 27, Erythropoiesis, Heme and Applications to Biomedicine. G.C. Ferreira, Ed. World Scientific, Singapore, pp 211-254.

2. Egan T.J. (2011). Biomimetic approaches to understanding the mechanism of haemozoin formation. On biomimetics. L. Pramatarova, Ed. Intech, Rijeka. pp 373-394.

1. Egan T.J. and Aisen P. (1995). Metal transferrin interactions. In A Handbook of metal-ligand interactions in biological fluids. Bioinorganic chemistry, Vol. 1, G. Berthon, Ed. Marcel Dekker, New York. pp 411-420.