Professor Kelly Chibale PhD (Cambridge) FRSSAf FRSC
Drug Discovery Group
Professor, Department of Chemistry, Faculty of Science; Member of the Institute of Infectious Disease and Molecular Medicine (IDM), UCT; Tier 1 South African National Research Chair in Drug Discovery under the South African Research Chairs Initiative; Director, South African Medical Research Council Drug Discovery and Development Research Unit; Founder and Director, UCT Drug Discovery and Development Centre (H3D)
Kelly Chibale’s drug discovery programme is driven within the H3D Centre at UCT, with laboratory and staff & students partially based in the IDM. Their current medicinal chemistry programme against the causative agents of malaria, tuberculosis and schistosomiasis infections has four main objectives:
- To identify hits from target- and phenotypic whole cell-based screening as medicinal chemistry starting points
- To progress hits via integrated interdisciplinary drug discovery underpinned by medicinal chemistry to deliver leads suitable for optimization and ultimately candidate selection
- To elucidate the mechanism of action of phenotypic whole cell hits through target identification
- To repurpose and/or reposition lead and clinical compounds
KCs earlier work has included asymmetric synthesis utilizing sulfur and organolanthanide chemistry as well as the total synthesis of natural and designed biologically active molecules.
Further details are found here [www.H3D.uct.ac.za]
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. K. Singh, J. Okombo, C. Brunschwig, F. Ndubi, L. Barnard, C. Wilkinson, P. M. Njogu, M. Njoroge, L. Laing, M. Machado, M. Prudêncio, J. Reader, M. Botha, S. Nondaba, L.-M. Birkholtz, S. Lauterbach, A. Churchyard, T. L. Coetzer, J. N. Burrows, C. Yeates, P. Denti, L. Wiesner, T. J. Egan, S. Wittlin, and K. Chibale*. J. Med. Chem. 2017, 60, 1432−1448.
Anti-malarial efficacy and parasite life cycle characterisation of the novel Plasmodium phosphatidylinositol 4-kinase inhibitor MMV390048. T. Paquet, C. Le Manach, D. González Cabrera, Y. Younis, P. P. Henrich, T. S. Abraham, M. C.S. Lee, R. Basak, S. Ghidelli-Disse, M. José Lafuente-Monasterio, M. Bantscheff, A. Ruecker, A. M. Blagborough, S.E. Zakutansky, A.-M. Zeeman, K. L. White, D. M. Shackleford, J. Mannila, J. Morizzi, C. Scheurer, I. Angulo-Barturen, M. S. Martínez, S. Ferrer, L. M. Sanz, F. Javier Gamo, J. Reader, M. Botha, K. J. Dechering, R. W. Sauerwein, A. Tungtaeng, P. Vanachayangkul, C. S. Lim, J. Burrows, M. J. Witty, K. C. Marsh, C. Bodenreider, R. Rochford, S.M. Solapure, M. B. Jiménez-Díaz, S. Wittlin, S. A. Charman, C. Donini, B. Campo, L.-M. Birkholtz, K. K. Hanson, G. Drewes, C. H.M. Kocken, M. J. Delves, D. Leroy, D.A. Fidock, D. Waterson, L. J. Street, and K. Chibale*. Sci. Transl. Med., 2017, 9 (Issue 387), eaad9735 DOI: 10.1126/scitranslmed.aad9735. Published online 26 Apr 2017.
Antischistosomal Activity of pyrido[1,2-a]benzimidazole derivatives and correlation with inhibition of β-haematin formation. J. Okombo, K. Singh, G. Mayoka, F. Ndubi, L. Barnard, P. M. Njogu, M. Njoroge, L. Gibhard, C. Brunschwig, M. Vargas, J. Keiser, T. J. Egan and K. Chibale* ACS Infect. Dis. 2017, 3, 411−420.
Insights into integrated lead generation and target identification in malaria and tuberculosis drug discovery J. Okombo and K. Chibale* Acc. Chem. Res. 2017, 50, 1606−1616.
Identification of new human malaria parasite Plasmodium falciparum dihydroorotate dehydrogenase inhibitors by pharmacophore and structure-based virtual screening. E. Pavadai, F. El Mazouni, S. Wittlin, C. de Kock, M. Phillips and K. Chibale* J. Chem. Inf. Model. 2016, 56, 548−562.
Identification of a potential anti-malarial drug candidate from a series of 2-aminopyrazines by optimization of aqueous solubility and potency across the parasite life-cycle. C. Le Manach, A.T. Nchinda, T. Paquet, D. G. Cabrera, Y. Younis, Z. Han, S. Bashyam, M. Zabiulla, D. Taylor, N. Lawrence, K. L. White, S. A. Charman, D. Waterson, M. J. Witty, S. Wittlin, M. E. Botha, S. H. Nondaba, J. Reader, L-M. Birkholtz, M. B. Jiménez-Díaz, M. S. Martínez, S. Ferrer, I. Angulo-Barturen, S. Meister, Y. Antonova-Koch, E. A. Winzeler, L. J. Street and K. Chibale* J. Med. Chem. 2016, 59, 9890−9905.
The dynamic non-prime binding of sampatrilat to the C-domain of angiotensin-converting enzyme. R. Sharma; M. Espinoza-Moraga; H. Poblete, R. Douglas, E. Sturrock; J. Caballero*, and K. Chibale* J. Chem. Inf. Model. 2016, 56, 2486−2494.
A novel pyrazolopyridine with in vivo activity in Plasmodium berghei and Plasmodium falciparum-infected mouse models from structure-activity relationship studies around the core of recently identified antimalarial imidazopyridazines. C. Le Manach, T. Paquet, C. Brunschwig, M. Njoroge, Z. Han, D. Gonzalez Cabrera, S. Bashyam, R. Dhinakaran, D. Taylor; J. Reader, M. Botha, A. Churchyard, S. Lauterbach, T. Coetzer, L.-M. Birkholtz, S. Meister, E. Winzeler, D. Waterson, M. Witty, S. Wittlin, M.-B., Jimenez-Diaz, M. Santos Martinez, S. Ferrer, I. Angulo-Barturen, L. Street and K. Chibale* J. Med. Chem. 2015, 58, 8713−8722.
Pyrrolo[3,4-c]pyridine-1,3(2H)-diones: a novel anti-mycobacterial class targeting mycobacterial respiration. R. van der Westhuyzen, S. Winks, C. R. Wilson, G. A. Boyle, R. K. Gessner, C. Soares de Melo, D. Taylor, C. de Kock, M. Njoroge, C. Brunschwig, N. Lawrence, S.P.S. Rao, F. Sirgel, P. van Helden, R. Seldon, A. Moosa, D. F. Warner, L. Arista, U. H. Manjunatha, P. W. Smith, L. J. Street, and K. Chibale* J. Med. Chem. 2015, 58, 9371−9381.
Fragment-based design for the development of N-domain-selective angiotensin-1-converting enzyme inhibitors. R.G. Douglas, R.K. Sharma, G. Masuyer, L. Lubbe, I. Zamora, K.R. Acharya*, K. Chibale* and E.D Sturrock* Clinical Science 2014, 126, 305−313.
Recent approaches to chemical discovery and development against malaria and the neglected tropical diseases human african trypanosomiasis and schistosomiasis. M. Njoroge, N. Njuguna, P. Mutai, D. Ongarora, P. Smith, and K. Chibale*. Chem. Rev. 2014, 114, 11138−11163.
Identification and characterization of reactive metabolites in natural products driven drug discovery. N. M. Njuguna. C. Masimirembwa, and K. Chibale* J. Nat. Prod. 2012, 75, 507-513.
3,5-Diaryl-2-aminopyridines as a novel class of orally active antimalarials demonstrating single dose cure in mice and clinical candidate potential. Y. Younis, F. Douelle, T.-S.Feng, D. González Cabrera, C. Le Manach, A. T. Nchinda, S. Duffy, K. L. White, D. M. Shackleford, J. Morizzi, J. Mannila, K. Katneni, R. Bhamidipati, K. M. Zabiulla, J. T. Joseph, S. Bashyam, D. Waterson, M. J. Witty, D. Hardick, S. Wittlin, V. Avery, S. A. Charman, and K. Chibale* J. Med. Chem. 2012, 55, 3479−3487.
Department of Chemistry & IDM
University of Cape Town
Tel: 27 (0)21 650 2553
Fax: 27 (0)21 650 4521
Details of group members including research officers, technical assistants, postdoctoral fellows and students: