Development of aminoquinoline-benzimidazole hybrids and their organometallic complexes as antimicrobial agents against Plasmodium falciparum and Mycobacterium tuberculosis
type: CreativeWork
description: Malaria and tuberculosis (TB) are infectious microbial diseases contributing to a major global health problem and remain a high priority.The problem is further compounded by the emergence of drug resistant strains of the respective causative agents. New therapies and drug design strategies are thus continually required to overcome this resistance. A unique approach in tackling rising resistance is the use of hybrid chemotherapy, which involves the combination of two or more pharmacophores into a single compound. This study investigated the synthesis, characterisation and pharmacological properties of new organic and ferrocenyl aminoquinoline-benzimidazole hybrid compounds, as well as the corresponding Platinum Group Metal (PGM)-containing complexes. The compounds were screened for their activity against Plasmodium falciparum, and for their cytotoxicity against the Chinese hamster ovarian (CHO) cell-line. In addition, the compounds were also evaluated against Mycobacterium tuberculosis. A series of aminoquinoline-benzimidazole hybrid compounds were prepared. The 2-position of the benzimidazole was substituted with an organic phenyl or pyridyl group, or an organometallic ferrocenyl group. The 5-position of the benzimidazole was varied using substituents with varying hydrophobic and electron-withdrawing or -donating properties, in order to probe the effect on biological activity. These compounds were fully characterised using 1H, 13C{1H}, COSY and HSQC NMR spectroscopy, IR spectroscopy and electrospray ionisation mass spectrometry. The organic and ferrocenyl aminoquinoline-benzimidazole hybrids were screened in vitro against the chloroquine-sensitive (CQS) NF54 strain and multidrug-resistant (MDR) K1 strain of P. falciparum. Most compounds displayed good activity against the sensitive NF54 strain, with IC50 values in the low to sub-micromolar range. With the exception of the pyridyl analogues, most compounds were more potent in the resistant K1 strain. Resistance indic…
abstract: Malaria and tuberculosis (TB) are infectious microbial diseases contributing to a major global health problem and remain a high priority.The problem is further compounded by the emergence of drug resistant strains of the respective causative agents. New therapies and drug design strategies are thus continually required to overcome this resistance. A unique approach in tackling rising resistance is the use of hybrid chemotherapy, which involves the combination of two or more pharmacophores into a single compound. This study investigated the synthesis, characterisation and pharmacological properties of new organic and ferrocenyl aminoquinoline-benzimidazole hybrid compounds, as well as the corresponding Platinum Group Metal (PGM)-containing complexes. The compounds were screened for their activity against Plasmodium falciparum, and for their cytotoxicity against the Chinese hamster ovarian (CHO) cell-line. In addition, the compounds were also evaluated against Mycobacterium tuberculosis. A series of aminoquinoline-benzimidazole hybrid compounds were prepared. The 2-position of the benzimidazole was substituted with an organic phenyl or pyridyl group, or an organometallic ferrocenyl group. The 5-position of the benzimidazole was varied using substituents with varying hydrophobic and electron-withdrawing or -donating properties, in order to probe the effect on biological activity. These compounds were fully characterised using 1H, 13C{1H}, COSY and HSQC NMR spectroscopy, IR spectroscopy and electrospray ionisation mass spectrometry. The organic and ferrocenyl aminoquinoline-benzimidazole hybrids were screened in vitro against the chloroquine-sensitive (CQS) NF54 strain and multidrug-resistant (MDR) K1 strain of P. falciparum. Most compounds displayed good activity against the sensitive NF54 strain, with IC50 values in the low to sub-micromolar range. With the exception of the pyridyl analogues, most compounds were more potent in the resistant K1 strain. Resistance indic…
author: Baartzes, Nadia
keywords: Chemistry
date published: 2020
date modified: 2026-07-22T22:23:49Z
provider: University of Cape Town
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Department of Chemistry

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11427/32196