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Gold(I) complex of 1,1'-bis(diphenylphosphino) ferrocene-quinoline conjugate: a virostatic agent against HIV-1.

Gama, Ntombenhle; Kumar, Kamlesh LU ; Ekengard, Erik LU ; Haukka, Matti; Darkwa, James; Nordlander, Ebbe LU and Meyer, Debra (2016) In Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 29(3). p.389-397
Abstract
HIV infection is known for replicating in proliferating CD(+) T-cells. Treatment of these cells with cytostatic (anti-proliferation) compounds such as hydroxyurea interferes with the cells's ability support HIV replication. Combinations of such cytostatic compounds with proven anti-retroviral drugs (like ddI) are known as virostatic, and have been shown to aid in the control of the infection. The use of two different drugs in virostatic combinations however, carries the risk of adverse effects including drug-drug interactions, which could lead to augmented toxicities and reduced efficacy. Here, a novel digold(I) complex of ferrocene-quinoline (3) was investigated for cytostatic behaviour as well as anti-viral activity which if demonstrated... (More)
HIV infection is known for replicating in proliferating CD(+) T-cells. Treatment of these cells with cytostatic (anti-proliferation) compounds such as hydroxyurea interferes with the cells's ability support HIV replication. Combinations of such cytostatic compounds with proven anti-retroviral drugs (like ddI) are known as virostatic, and have been shown to aid in the control of the infection. The use of two different drugs in virostatic combinations however, carries the risk of adverse effects including drug-drug interactions, which could lead to augmented toxicities and reduced efficacy. Here, a novel digold(I) complex of ferrocene-quinoline (3) was investigated for cytostatic behaviour as well as anti-viral activity which if demonstrated would eliminate concerns of drug-drug interactions. The complex was synthesized and characterized by NMR, FT-IR and mass spectroscopy and the molecular structure was confirmed by X-ray crystallography. Bio-screening involved viability dyes, real time electronic sensing and whole virus assays. The complex showed significant (p = 0.0092) inhibition of virus infectivity (83 %) at 10 ug/mL. This same concentration caused cytostatic behaviour in TZM-bl cells with significant (p < 0.01) S and G2/M phase cell cycle arrest. These data supports 3 as a virostatic agent, possessing both anti-viral and cytostatic characteristics. In the absence of 3, TZM-bl cells were infected by a pseudovirus and this was demonstrated through luminescence in a luciferase assay. Pre-incubation of the virus with 3 decreased luminescence, indicating the anti-viral activity of 3. Complex 3 also showed cytostatic behavior with increased S-phase and G2/M phase cell cycle arrest. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine
volume
29
issue
3
pages
9 pages
publisher
Springer
external identifiers
  • pmid:26922346
  • scopus:84971505201
  • wos:000376682100003
ISSN
1572-8773
DOI
10.1007/s10534-016-9921-9
language
English
LU publication?
yes
id
8113c08d-2ceb-421a-ba70-e0e6b2a5a652 (old id 8821423)
date added to LUP
2016-03-11 11:30:58
date last changed
2017-04-21 13:25:51
@article{8113c08d-2ceb-421a-ba70-e0e6b2a5a652,
  abstract     = {HIV infection is known for replicating in proliferating CD(+) T-cells. Treatment of these cells with cytostatic (anti-proliferation) compounds such as hydroxyurea interferes with the cells's ability support HIV replication. Combinations of such cytostatic compounds with proven anti-retroviral drugs (like ddI) are known as virostatic, and have been shown to aid in the control of the infection. The use of two different drugs in virostatic combinations however, carries the risk of adverse effects including drug-drug interactions, which could lead to augmented toxicities and reduced efficacy. Here, a novel digold(I) complex of ferrocene-quinoline (3) was investigated for cytostatic behaviour as well as anti-viral activity which if demonstrated would eliminate concerns of drug-drug interactions. The complex was synthesized and characterized by NMR, FT-IR and mass spectroscopy and the molecular structure was confirmed by X-ray crystallography. Bio-screening involved viability dyes, real time electronic sensing and whole virus assays. The complex showed significant (p = 0.0092) inhibition of virus infectivity (83 %) at 10 ug/mL. This same concentration caused cytostatic behaviour in TZM-bl cells with significant (p &lt; 0.01) S and G2/M phase cell cycle arrest. These data supports 3 as a virostatic agent, possessing both anti-viral and cytostatic characteristics. In the absence of 3, TZM-bl cells were infected by a pseudovirus and this was demonstrated through luminescence in a luciferase assay. Pre-incubation of the virus with 3 decreased luminescence, indicating the anti-viral activity of 3. Complex 3 also showed cytostatic behavior with increased S-phase and G2/M phase cell cycle arrest.},
  author       = {Gama, Ntombenhle and Kumar, Kamlesh and Ekengard, Erik and Haukka, Matti and Darkwa, James and Nordlander, Ebbe and Meyer, Debra},
  issn         = {1572-8773},
  language     = {eng},
  number       = {3},
  pages        = {389--397},
  publisher    = {Springer},
  series       = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine},
  title        = {Gold(I) complex of 1,1'-bis(diphenylphosphino) ferrocene-quinoline conjugate: a virostatic agent against HIV-1.},
  url          = {http://dx.doi.org/10.1007/s10534-016-9921-9},
  volume       = {29},
  year         = {2016},
}