RESEARCH INTERESTS
Our current medicinal chemistry programme on novel
anti-infective (anti-malarial, anti-tuberculosis, anti-HIV/AIDS and
anti-trypanosomal), anti-hypertension and anti-cancer agents has three
main objectives:
(i) to develop target-directed inhibitors
(ii) to develop single agents that provide target-directed
inhibition of multiple disease-causing organisms or cells
(iii) to develop single agents that provide maximal anti-infective and
anti-cancer activity by acting against multiple targets.
Earlier work has included asymmetric synthesis utilizing sulfur and
organolanthanide chemistry, the total synthesis of natural and designed
molecules and the design and synthesis of non-peptide inhibitors of
angiogenesis as potential anti-cancer agents.
All our medicinal chemistry projects are collaborative
and multidisciplinary in nature. They broadly involve aspects of synthetic
organic chemistry, chemical biology, biochemistry, molecular biology,
pharmacology, computational chemistry and molecular modeling.
REPRESENTATIVE PUBLICATIONS
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.
The synthesis of parasitic cysteine protease
and trypanothione reductase inhibitors, K. Chibale and C. C.
Musonda Curr. Med. Chem. 2003, 10, 1863-1889.
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.
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.
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.
Novel approaches to antimalarial drug
discovery. C. Biot, and K. Chibale, Infectious Disorders- Drug
Targets-, 2006, 6, 173-204.
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