Impedance technology reveals correlations between cytotoxicity and lipophilicity of mono and bimetallic phosphine complexes

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dc.contributor.author Fonteh, Pascaline Nanga
dc.contributor.author Elkhadir, A.
dc.contributor.author Omondi, B.
dc.contributor.author Guzei, I.
dc.contributor.author Darkwa, J.
dc.contributor.author Meyer, Debra
dc.date.accessioned 2015-08-13T05:58:19Z
dc.date.available 2015-08-13T05:58:19Z
dc.date.issued 2015-08
dc.description.abstract Label free impedance technology enables the monitoring of cell response patterns post treatment with drugs or other chemicals. Using this technology, a correlation between the lipophilicity of metal complexes and the degree of cytotoxicity was observed. Au(L1)Cl (1), AuPd(L1)(SC4H8)Cl3 (1a) and Au(L2)Cl (2) [L1 = diphenylphosphino-2-pyridine; L2 = 2-(2-(diphenylphosphino)ethyl)-pyridine] were synthesised, in silico drug-likeness and structure– activity relationship monitored using impedance technology. Dose dependent changes in cytotoxicity were observed for the metal complexes resulting in IC50s of 12.5 ± 2.5, 18.3 ± 8.3 and 16.9 ± 0.5 lM for 1, 1a and 2 respectively in an endpoint assay. When a real time impedance assay was used, dose-dependent responses depicting patterns that suggested slower uptake (at a toxic 20 lM) and faster recovery of the cells (at the less toxic 10 lM) of the bimetallic complex (1a) compared to the monometallic complexes (1 and 2) was observed. These data agreed with the ADMET findings of lower aqueous solubility of 1a and non-ideal lipophilicity (AlogP98 of 6.55) over more water soluble 1 and 2 with ideal lipophilicity (4.91 and 5.03 respectively) values. The additional coordination of a Pd atom to the nitrogen atom of a pyridine ring, the sulfur atom of a tetrahydrothiophene moiety and two chlorine atoms in 1a could be contributing to the observed differences when compared to the monometallic complexes. This report presents impedance technology as a means of correlating drug-likeness of lipophilic phosphine complexes containing similar backbone structures and could prove valuable in filtering drug-like compounds in a drug discovery project. en_ZA
dc.description.embargo 2016-08-31 en_ZA
dc.description.librarian hb2015 en_ZA
dc.description.sponsorship Technology Innovation Agency (TIA), the University of Pretoria.Organization for Women in Science for the Developing World (OWSD) formerly Third World Organization for Women in Science (TWOWS) and University of Johannesburg. en_ZA
dc.description.uri http://link.springer.com/journal/10534 en_ZA
dc.identifier.citation Fonteh, P, Elkhadir, A, Omondi, B, Guzei, I, Darkwa, J & Meyer, D 2015, 'Impedance technology reveals correlations between cytotoxicity and lipophilicity of mono and bimetallic phosphine complexes', BioMetals, vol. 28, no. 4, pp. 653-667. en_ZA
dc.identifier.issn 0966-0844 (print)
dc.identifier.issn 1572-8773 (online)
dc.identifier.other 10.1007/s10534-015-9851-y
dc.identifier.uri http://hdl.handle.net/2263/49263
dc.language.iso en en_ZA
dc.publisher Springer en_ZA
dc.rights © Springer Science+Business Media New York 2015. The original publication is available at : http://link.springer.comjournal/10534. en_ZA
dc.subject Impedance en_ZA
dc.subject Cytotoxicity en_ZA
dc.subject Uptake en_ZA
dc.subject Recovery en_ZA
dc.subject Lipophilicity en_ZA
dc.subject Phosphine gold complexes en_ZA
dc.title Impedance technology reveals correlations between cytotoxicity and lipophilicity of mono and bimetallic phosphine complexes en_ZA
dc.type Postprint Article en_ZA


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