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Drug Discovery and Development Research Unit

Publications

2000

1. Synthesis and Evaluation of 9,9-Dimethylxanthene Tricyclics Against Trypanothione Reductase, Trypanosoma brucei, Trypanosoma cruzi and Leishmania donovani. K. Chibale*, M. Visser, V. Yardley, S.L. Croft and A.H. Fairlamb. Bioorg. Med. Chem, Letts 2000, 10, 1147-1150.  
2. New Amine and Urea Analogs of Ferrochloroquine: Synthesis, Antimalarial Activity In Vitro and Electrochemical Studies. K. Chibale*, J.R. Moss, M. Blackie, D. van Schalkwyk and P.J. Smith. Tetrahedron Letts 2000, 41, 6231-6235. 
3. The Lewis Base Behaviour of Copper(I) Nitroxyl Free Radical Complex (CuL2)-Reaction with AceticAcid. E.M.R. Kiremire*, G. Kumar, K. Chibale, J.C.A. Boeyens and J. van Wyk. Oriental Journal of Chemistry  2000, 16(3), 451-452.

2001

1. The Synthesis and Characterization of the First Tris-Chelate Complexes of Vanadium(III), Chromium(III) and Manganese(III) containing Deprotonated 4-Phenylacetylidene-2,2,5,5-Tetramethylimidazolidin-1-oxyl Nitroxyl Free Radical Ligand. E.M.R. Kiremire*, G. Kumar, H. Muwowo, K. Chibale, J.C.A. Boeyens, J. van Wyk and G.N. Kamau. Oriental Journal of Chemistry  2001, 17(1), 37-42.
2. Modulation of Human Mammary Cell Sensitivity to Paclitaxel by New Quinoline Sulfonamides.  K. Chibale*, I. Ojima, H. Haupt, X. Geng, P. Pera and R. J. Bernacki. Bioorg. Med. Chem. Letts. 2001, 11, 2457-2460.  
3. Antiprotozoal and Cytotoxicity Evaluation of Sulfonamide and Urea Analogs of Quinacrine.K. Chibale*, H. Haupt, H. Kendrick, V. Yardley, A. Saravanamuthu, A.H. Fairlamb and S.L. Croft. Bioorg. Med. Chem. Letts. 2001, 11, 2655-2657. 

2002

1. A Novel and Efficient Regiospecific Preparation of Arenesulfonamide Derivatives of 3,5-Diamino-1,2,4-triazole.K. Chibale*, J. Dauvergne and P. J. Wyatt. Synthesis, 2002, 185- 190 
2. Convenient synthesis of disulfide substrates for trypanothione reductase using polymer-supported reagents.  K. Chibale*, A. Chipeleme and S. Warren.  Tetrahedron Lett., 2002, 43(8), 1587-1589. 
3. A Chemical Approach towards Understanding the Mechanism and Reversal of Drug Resistance in Plasmodium falciparum: Is it Viable? K. Chibale*. International Union of Biochemistry and Molecular Biology (IUBMB) Life, 2002, 53, 249-252.  
4. Synthesis and antimalarial activity in vitro of new ruthenocene-chloroquine analogues.  P. Beagley, M. A. L. Blackie, K. Chibale*, C. Clarkson, J. R. Moss* and P. J. Smith.  J. Chem. Soc., Dalton. Trans., 2002, 4426-4433.  
5. Towards broadspectrum antiparasitic agents, K. Chibale*, ARKIVOC, 2002, (ix), 93-98 

2003

1. Design, synthesis, and evaluation of taxanes as potential antimalarial agents. J Chen, L Kuznetsova, K Chibale, I Ojima et al.  Abstracts of Papers of the American Chemical Society   2003, 226, U48-U48    
2. Exploring the potential of xanthene derivatives as trypanothione reductase inhibitors and chloroquine potentiating agents.  K. Chibale*, M. R. Visser, D. van Schalkwyk, P. J. Smith, A. Saravanamuthu and A. H. Fairlamb. Tetrahedron, 2003, 59, 2289-2296.  
3. The synthesis of parasitic cysteine protease and trypanothione reductase inhibitors, K. Chibale* and C. C. Musonda.  Curr. Med. Chem. 2003, 10, 1863-1889.  
4. Synthesis and Antiplasmodial Activity in vitro of New Ferrocene-chloroquine Analogues.  P. Beagley, M. A. L. Blackie, K. Chibale,* C. Clarkson, R. Meijboom, J. R. Moss,* P. J. Smithand H. Su. Dalton Transactions, 2003, 3046- 3051.  
5. Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain.  I. Chiyanzu, E. Hansell, J. Gut, P. J. Rosenthal, J. H. McKerrow and K. Chibale*. Bioorg. Med. Chem. Letts. 2003. 13, 3527-3530. 
6. Synthesis and antimalarial activity in vitro of new heterobimetallic complexes:  Rh and Au derivatives of chloroquine and a series of ferrocenyl-4-amino-7chloroquinolines.  M. A. L. Blackie, P. Beagley, K. Chibale, C. Clarkson, A. T. Hutton, J. R. Moss* and P. J. Smith. J. Organomet. Chem. 2003, 688, 144-152.  
7. Synthesis of totarol amino alcohol derivatives and their antiplasmodial activity and cytotoxicity.  C. Clarkson, C. C. Musonda, K. Chibale*, W. E. Campbell and P. J. Smith.  Bioorg. Med. Chem, 2003, 11, 4417-4422.   

2004

1. Unprecedented observation of sulfonamides in the transesterification of N-unsubstituted carbamates with sulfonly chlorides.  J. Dauvergne, K. Wellington and K. Chibale*. Tetrahedron Lett., 2004, 45, 43-47 
2. Application of combinatorial and parallel synthesis methodologies to antiparasite drug discovery, C. C. Musonda and K. Chibale*. Curr. Med. Chem. 2004, 11, 2519-2533.  
3. Synthesis and Structure Activity Relationships of Parasiticidal Thiosemicarbazone Cysteine Protease Inhibitors against P.falciparum, T. brucei and T. cruzi.  D. Greenbaum*, Z. Mackey, E. Hansell, P. Doyle, J. Gut, C. R. Caffrey, J. Lehman, P. J. Rosenthal, J. H. McKerrow, and K. Chibale*.  J. Med. Chem. 2004, 47, 3212-3219.  
4. Application of Multi-Component Reactions to Antimalarial Drug Discovery. Part 1.  Parallel Synthesis and Antiplasmodial Activity of New 4-Aminoquinoline Ugi Adducts. C. C. Musonda, D. Taylor, J. Lehman, J. Gut, P. J. Rosenthal and K. Chibale*. Bioorg. Med. Chem. Letts., 2004, 14, 3901-3905. 

2005

1. The new permeability pathways: targets and selective routes for the development of new antimalarial agents. H. M. Staines*, J. C. Ellory and K. Chibale. Combinatorial Chemistry and High Throughput Screening  2005, 8, 81-88.  
2. Design, synthesis and antiplasmodial evaluation in vitro of new 4-aminoquinoline isatin derivatives.  I. Chiyanzu, C. Clarkson, P. J. Smith, J. Lehman, J. Gut. P. J. Rosenthal and K. Chibale*. Bioorg. Med. Chem., 2005, 13, 3249-3261.  
3. Exploiting a basic chemosensitizing pharmacophore hypothesis. Part 1: synthesis and biological evaluation of novel arylbromide and bicyclic chemosensitizers against drug-resistant malaria parasites F. Chouteau, D. Ramanitrahasimbola, P. Rasoanaivo* and K. Chibale*. Bioorg. Med. Chem. Letts., 2005, 15, 3024-3028. 
4. Reversal of chloroquine resistance in Plasmodium falciparum by 9H-xanthene derivatives. C.-P. Wu, D. A. van Schalkwyk, D. Taylor, P. J. Smith and K. Chibale*. International Journal of Antimicrobial Agents 2005, 26, 170-175  
5. Economic drug discovery and rational medicinal chemistry for tropical diseases. K. Chibale*. Pure & Applied Chemistry 2005, 77, 1957-1964. 
6. Arylpiperazines displaying preferential potency against chloroquine-resistant strains of the malaria parasite Plasmodium falciparum.  C.-A. Molyneaux, M. Krugliak, H. Ginsburg, and K. Chibale*.Biochemical Pharmacology. 2005, 71, 61-68. 

2006

1. Inhibitors of the trypanosome alternative oxidase reduce parasite growth in culture.  RD Ott, K Chibale, S Anderson, A Chipeleme, M Chaudhuri, N Colowick, and G C Hill.  Faseb J.   2006  20 A938-A938  
2. Novel Ketomethylene Inhibitors of Angiotensin-I Converting Enzyme (ACE): Inhibition and Molecular Modelling.  P. Redelinghuys, A. T. Nchinda, K. Chibale and E. D. Sturrock*.Biological Chemistry, 2006, 387, 461-466.  
3. Novel approaches to antimalarial drug discovery.  C. Biot*, and K. Chibale*. Infectious Disorders- Drug Targets-, 2006, 6, 173-204.
4. Application of Multi-Component Reactions to Antimalarial Drug Discovery. Part 2.  New Antiplasmodial and Antitrypanosomal 4- Aminoquinoline  γ– and δ Lactams via a “Catch and Release” Protocol.  C. C. Musonda, J. Gut, P. J. Rosenthal V. Yardley, R. C. Carvalho de Souza and K. Chibale*. Bioorg. Med. Chem.  2006, 14, 5605-5615.  
5. Dual-Acting Diamine Antiplasmodial and Chloroquine Resistance Modulating Agents.  S. Yeh, P. J. Smith and K. Chibale*.   Biochemical Pharmacology 2006, 72, 156-165.  
6. Synthesis of Novel Keto-ACE Analogues as Domain-Selective Angiotensin-I Converting Enzyme Inhibitors A. T. Nchinda, K. Chibale, P. Redelinghuys, and E. D. Sturrock*. Bioorg. Med. Chem Lett.  2006, 16, 4612-4615.  
7. Synthesis and Molecular Modeling of a Lisinopril-Tryptophan Analogue Inhibitor of Angiotensin I-Converting Enzyme.  A. T. Nchinda, K. Chibale, P. Redelinghuys, and E. D. Sturrock*. Bioorg. Med. Chem Lett.  2006, 16, 4616-4619. 
8. Novel inhibitors of the trypanosome alternative oxidase inhibit Trypanosoma brucei brucei growth and respiration.  R. Ott, K. Chibale, S. Anderson, A. Chipeleme, M. Chaudhuri, A. Guerrah, N. Colowick, and G. C. Hill*.  Acta Tropica 2006, 100, 172-184. 

2007

1. Synthesis and Biological Evaluation of Phenolic Mannich Bases of Benzaldehyde and (thio) semicarbazone derivatives Against the Cystein Protease falcipain-2 and a chloroquine resistant strain of Plasmodium falciparum.  A. Chipeleme, J. Gut, P. J. Rosenthal and K.  Chibale*. Bioorg. Med. Chem.  2007, 15, 273-282.  
2. Purification of human malaria parasite hypoxanthine guanine xanthine phosphoribosyltransferase (HGXPRT) using immobilized Reactive Red 120.  B. Mbewe*, K. Chibale and D. B. McIntosh. Protein Expression and Purification 2007, 52, 153-158.  
3. Antiplasmodial hirsutinolides from Vernonia staehelinoides and their utilization towards a novel simplified pharmacophore.  P. Pillay*, R. Vleggaar, V. J. Maharaj, P. J. Smith, C. A. Lategan,. F. Chouteau and K. Chibale. Phytochemistry 2007, 68, 1200-1205.  
4. Application of Multicomponent Reactions to Antimalarial Drug Discovery. Part 3: Discovery of aminoxazole 4-aminoquinolines with potent antiplasmodial activity in vitro Part 3.  C.C. Musonda, S. Little, V. Yardley and K. Chibale*. Bioorg. Med. Chem Lett.  2007, 17, 4733-4736. 
5. Metallocene-based antimalarials: An exploration into the influence of the ferrocenyl moiety on in vitro antimalarial activity in chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum.  M.A.L. Blackie, P. Beagley, S. L. Croft, H. Kendrick, J. R. Moss and K. Chibale*. Bioorg. Med. Chem.  2007, 15, 6510-6516.   
6. Synthesis of new 7-chloroquinolinyl thioureas and their biological investigation as potential anti-malarial and anticancer agents. A. Mahajan, S. Yeh, M. Nell, C E J van Rensburg and K. Chibale*. Bioorg. Med. Chem Lett.  2007, 17, 5683-5685.  
7. Design, synthesis, and antimalarial activity of structural chimeras of thiosemicarbazone and ferroquine analogues. C. Biot,* B. Pradines, M-H. Sergeant, J. Gut, P. J. Rosenthal and K. Chibale. Bioorg. Med. Chem Lett.  2007, 17, 6434-6438  
8. Chemoselectivity and unusual internal acetal formation in the synthesis of a glycosidation precursor. A. T. Stevens, J. R. Bull and K. Chibale*.  Synlett  2007, 3175-3179.  

2008

1. Effect of varying the anionic component of a copper (I) catalyst on homologation of arylacetylenes to allenes by the Mannich reaction. V. Kumar, A. Chipeleme and K. Chibale*. Eur. J. Org. Chem.  2008, 43-46.  
2. Studies in Iridoid Synthesis. Chemoselective Transformations of Cis-1,2,4,6-Tetrahydrophthalic Anhydride. A. T. Stevens, J. R. Bull and K. Chibale*. Org. Biomol. Chem., 2008, 6, 586-595. 
3. Meclonazepam Analogues as Potential New Antihelmintic Agents. A. Mahajan, V. Kumar, N. R. N. Mansour, Q. Bickle and K. Chibale*.Bioorg. Med. Chem Lett. 2008, 18, 2333-2336  
4. Metallocene Antimalarials: The Continuing Quest. M. A. L. Blackie and K. Chibale*. Metal-Based Drugs, 2008, 2008, 495123 doi:10.1155/2008/495123
5. Inhibition of Trypanothione Reductase and Glutathione Reductase by Ferrocenic 4-Aminoquinoline Ureas. M. A. L. Blackie, A. Saravanamuthu, A. H. Fairlamb and K. Chibale*. Arkivoc, 2008, (vi), 52-60 
6. Synthesis, antimalarial and cytotoxic evaluation of reversed chloroquines based on the 3,4-dihydropyrimidi-2(1H)-one scaffold. N. October, N. D. Watermeyer, V. Yardley, T. J. Egan, K. Ncokazi and K. Chibale*. ChemMedChem.  2008, 3, 1649-1653.
7. Antiplasmodial, -haematin inhibition, antitrypanosomal and cytotoxic activity in vitro of novel 4-aminoquinoline 2-imidazolines. C.C. Musonda, V.Yardley, R. C. Carvalho de Souza, K. Ncokazi, T. J. Egan and K. Chibale*.  Org. Biomol. Chem., 2008, 6, 4446 – 4451  

2009

1. Synthetic Medicinal Chemistry of Antimalarial Natural Products. V. Kumar, A. Mahajan, and K. Chibale*. Bioorg. Med. Chem.  2009, 17, 2236-2275.   
2. Novel web-based tools combining chemistry informatics, biology and social networks for drug discovery. M. Hohman, K. Gregory, K. Chibale, P.J. Smith, S. Ekins and B. Bunin*. Drug Discovery Today, 2009,14, 261-70.
3. Synthesis of novel anti-2-alkoxy-3-amino-3-arylpropan-1-ols and cis-5-alkoxy-4aryl-1,3-oxazinanes with antimalarial activity. M. D’hooghe, P. J. Smith, S. Dekeukeleire, K. Mollet, K. Chibale and N. De Kimpe* J. Med. Chem.  2009, 52, 4058-4062.
4. Cycloaddition and One-Carbon Homologation Studies in the Synthesis of Advanced Iridoid Precursors. A. T. Stevens, M. R. Caira, J. R. Bull, and K. Chibale* Org. Biomol. Chem., 2009, DOI:10.1039/b902452b, accepted for publication, in press
5. Pharmacologically relevant bifunctional compounds containing chloroquinoline and dihydropyrimidone moieties; syntheses and crystal structures of a target molecule and selected intermediates. N. D. Watermeyer, K. Chibale* and M.R. Caira*.  J. Chem. Crystallography.  2009, accepted for publication, in press