dc.contributor.author |
Fonteh, Pascaline Nanga
|
|
dc.contributor.author |
Keter, Frankline K.
|
|
dc.contributor.author |
Meyer, Debra
|
|
dc.date.accessioned |
2012-06-06T11:32:45Z |
|
dc.date.available |
2012-06-06T11:32:45Z |
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dc.date.issued |
2011-09 |
|
dc.description.abstract |
Four bis(thiosemicarbazonate)gold(III) complexes (1–4) with a general formula [Au(L)]Cl {L=L1, glyoxal-bis
(N4-methylthiosemicarbazone); L2, glyoxal-bis(N4-ethylthiosemicarbazone); L3, diacetyl-bis(N4-
methylthiosemicarbazone); L4, diacetyl-bis(N4-ethylthiosemicarbazone)} were synthesised and screened
for activity against the human immunodeficiency virus (HIV). Complexes 1–4 were characterised using
1H-NMR and IR spectroscopy; and their purity established by micronanalysis. Complex 3 inhibited viral
infection of TZM-bl cells by 98% (IC50=6.8±0.6 μM) at a non toxic concentration of 12.5 μM while
complex 4 inhibited infection of these cells by 72 and 98% (IC50=5.3±0.4 μM) at concentrations of 6.25
and 12.5 μMrespectively. Themechanism of inhibition of infection in TZM-bl cells is presumably as a result
of the cytostatic or anti-proliferative activity that was observed for complex 4 in real time cell electronic
sensing (RT-CES) and carboxyflourescein succinimidyl ester (CFSE) analysis. Treatment of T lymphocytes
from HIV infected individuals with 4 decreased CD4+ T cell expression (p=0.0049) as demonstrated by
multi-parametric flow cytometry without suppressing cytokine production. None of the ligands (L1–L4)
demonstrated anti-viral activity, supporting the importance of metal (gold) complexation in these potential drugs.
Complexes 3 and 4were shown to have ideal lipophilicity values thatwere similarwhenshake flask (0.97±0.5 and
2.42±0.6) and in silico prediction (0.8 and 1.5) methods were compared. The activity and drug-like properties of
complexes 3 and 4 suggests that these novel metal-based compounds could be combined with virus inhibitory
drugs to work as cytostatic agents in the emerging class of anti-HIV drugs known as virostatics. |
en |
dc.description.librarian |
nf2012 |
en |
dc.description.sponsorship |
The South African National Research Foundation |
en_US |
dc.description.uri |
http://www.elsevier.com/locate/jinorgbio |
en_US |
dc.identifier.citation |
Pascaline N. Fonteh, Frankline K. Keter & Debra Meyer, New bis(thiosemicarbazonate) gold(III) complexes inhibit HIV replication at cytostatic concentrations : potential for incorporation into virostatic cocktails, Journal of Inorganic Biochemistry, vol. 105, no. 9, pp. 1173-1180 (2011), doi: 10.1016/j.jinorgbio.2011.05.011 |
en |
dc.identifier.issn |
0162-0134 (print) |
|
dc.identifier.issn |
1873-3344 (online) |
|
dc.identifier.other |
10.1016/j.jinorgbio.2011.05.011 |
|
dc.identifier.uri |
http://hdl.handle.net/2263/19127 |
|
dc.language.iso |
en |
en_US |
dc.publisher |
Elsevier |
en_US |
dc.rights |
© 2011 Elsevier Inc. All rights reserved. |
en_US |
dc.subject |
Bis(thiosemicarbazonate) gold(III) complexes |
en |
dc.subject |
Anti-HIV agents |
en |
dc.subject |
Cytostasis |
en |
dc.subject.lcsh |
HIV infections |
en |
dc.subject.lcsh |
AIDS (Disease) -- Treatment -- Research |
en |
dc.subject.lcsh |
Chemical inhibitors |
en |
dc.subject.lcsh |
Immune response |
en |
dc.title |
New bis(thiosemicarbazonate) gold(III) complexes inhibit HIV replication at cytostatic concentrations : potential for incorporation into virostatic cocktails |
en |
dc.type |
Postprint Article |
en |