Onajole O.K., Govender K., Govender P., van Helden P.D., Kruger H.G., Maguire G.E.M., Muthusamy K., Pillay M., Wiid I., Govender T.
School of Chemistry, University of KwaZulu-Natal, Durban, South Africa; Department of Medical Microbiology, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; Department of Biochemistry, University of KwaZulu-Natal, Durban, South Africa; Department of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa; School of Pharmacy and Pharmacology, University of KwaZulu-Natal, Durban, South Africa
Onajole, O.K., School of Chemistry, University of KwaZulu-Natal, Durban, South Africa; Govender, K., Department of Medical Microbiology, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; Govender, P., Department of Biochemistry, University of KwaZulu-Natal, Durban, South Africa; van Helden, P.D., Department of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa; Kruger, H.G., School of Chemistry, University of KwaZulu-Natal, Durban, South Africa; Maguire, G.E.M., School of Chemistry, University of KwaZulu-Natal, Durban, South Africa; Muthusamy, K., Department of Biochemistry, University of KwaZulu-Natal, Durban, South Africa; Pillay, M., Department of Medical Microbiology, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; Wiid, I., Department of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa; Govender, T., School of Pharmacy and Pharmacology, University of KwaZulu-Natal, Durban, South Africa
As part of an ongoing effort to develop highly potent anti-tuberculosis agents, fourteen pentacyclo-undecane (PCU) tetra-amine compounds were synthesized and screened for their in vitro anti-mycobacterial activity against two TB strains, H37Rv and XDR 194 [an extensively drug-resistant strain of tuberculosis]. Using the broth macrodilution method, nitrofuranylamide based compounds (6a and 6b) showed almost similar activities against the H37Rv strain of Mycobacterium tuberculosis when compared with the control drug, ethambutol. N-Geranyl piperazine PCU (8a) and trans-trans farnesyl piperazine PCU (8b) were 3.2 and 3.7 times more potent than commercially available ethambutol. Both isoprenyl PCU tetra-amine derivatives and N-decyl piperazine PCU (9a) were highly active against the XDR 194 strain of tuberculosis with MICs in the range of 0.63-3.02 μM. Cytotoxicities (IC50) of isoprenyl based compounds (8a, 8b) and compound 9a were tested on a mammalian cell line [MDBK (Madin Darby bovine kidney epithelium)] with values of 30, 24 and 25 μM respectively. © 2009 Elsevier Masson SAS. All rights reserved.