Investigating the chemical space and metabolic bioactivation of natural products and cross-reactivity of chemical inhibitors in CYP450 phenotyping

 

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dc.contributor.advisor Chibale, Kelly en_ZA
dc.contributor.author Njuguna, Nicholas M en_ZA
dc.date.accessioned 2015-05-27T04:10:41Z
dc.date.available 2015-05-27T04:10:41Z
dc.date.issued 2014 en_ZA
dc.identifier.citation Njuguna, N. 2014. Investigating the chemical space and metabolic bioactivation of natural products and cross-reactivity of chemical inhibitors in CYP450 phenotyping. University of Cape Town. en_ZA
dc.identifier.uri http://hdl.handle.net/11427/12927
dc.description Includes bibliographical references. en_ZA
dc.description.abstract Natural products have been exploited by humans as the most consistently reliable source of medicines for hundreds of years. Owing to the great diversity in chemical scaffolds they encompass, these compounds provide an almost limitless starting point for the discovery and development of novel semi-synthetic or wholly synthetic drugs. In Africa, and many other parts of the world, natural products in the form of herbal remedies are still used as primary therapeutic interventions by populations far removed from conventional healthcare facilities. However, unlike conventional drugs that typically undergo extensive safety studies during development, traditional remedies are often not subjected to similar evaluation and could therefore harbour unforeseen risks alongside their established efficacy. A comparison of the ‘drug-like properties’ of 335 natural products from medicinal plants reported in the African Herbal Pharmacopoeia with those of 608 compounds from the British Pharmacopoeia 2009 was performed using in silico tools. The data obtained showed that the natural products differed significantly from conventional drugs with regard to molecular weight, rotatable bonds and H-bond donor distributions but not with regard to lipophilicity (cLogP) and H-bond acceptor distributions. In general, the natural products were found to exhibit a higher degree of deviation from Lipinski’s ‘Rule-of-Five’. Additionally, these compounds possessed a slightly greater number of structural alerts per molecule compared to conventional drugs, suggesting a higher likelihood of undergoing metabolic bioactivation. en_ZA
dc.language.iso eng en_ZA
dc.subject.other Chemistry en_ZA
dc.title Investigating the chemical space and metabolic bioactivation of natural products and cross-reactivity of chemical inhibitors in CYP450 phenotyping en_ZA
dc.type Doctoral Thesis
uct.type.publication Research en_ZA
uct.type.resource Thesis en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Science en_ZA
dc.publisher.department Department of Chemistry en_ZA
dc.type.qualificationlevel Doctoral
dc.type.qualificationname PhD en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Njuguna, N. M. (2014). <i>Investigating the chemical space and metabolic bioactivation of natural products and cross-reactivity of chemical inhibitors in CYP450 phenotyping</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/12927 en_ZA
dc.identifier.chicagocitation Njuguna, Nicholas M. <i>"Investigating the chemical space and metabolic bioactivation of natural products and cross-reactivity of chemical inhibitors in CYP450 phenotyping."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2014. http://hdl.handle.net/11427/12927 en_ZA
dc.identifier.vancouvercitation Njuguna NM. Investigating the chemical space and metabolic bioactivation of natural products and cross-reactivity of chemical inhibitors in CYP450 phenotyping. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2014 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/12927 en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Njuguna, Nicholas M AB - Natural products have been exploited by humans as the most consistently reliable source of medicines for hundreds of years. Owing to the great diversity in chemical scaffolds they encompass, these compounds provide an almost limitless starting point for the discovery and development of novel semi-synthetic or wholly synthetic drugs. In Africa, and many other parts of the world, natural products in the form of herbal remedies are still used as primary therapeutic interventions by populations far removed from conventional healthcare facilities. However, unlike conventional drugs that typically undergo extensive safety studies during development, traditional remedies are often not subjected to similar evaluation and could therefore harbour unforeseen risks alongside their established efficacy. A comparison of the ‘drug-like properties’ of 335 natural products from medicinal plants reported in the African Herbal Pharmacopoeia with those of 608 compounds from the British Pharmacopoeia 2009 was performed using in silico tools. The data obtained showed that the natural products differed significantly from conventional drugs with regard to molecular weight, rotatable bonds and H-bond donor distributions but not with regard to lipophilicity (cLogP) and H-bond acceptor distributions. In general, the natural products were found to exhibit a higher degree of deviation from Lipinski’s ‘Rule-of-Five’. Additionally, these compounds possessed a slightly greater number of structural alerts per molecule compared to conventional drugs, suggesting a higher likelihood of undergoing metabolic bioactivation. DA - 2014 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Investigating the chemical space and metabolic bioactivation of natural products and cross-reactivity of chemical inhibitors in CYP450 phenotyping TI - Investigating the chemical space and metabolic bioactivation of natural products and cross-reactivity of chemical inhibitors in CYP450 phenotyping UR - http://hdl.handle.net/11427/12927 ER - en_ZA


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