Gold(I) complex of 1,1'-bis(diphenylphosphino) ferrocene-quinoline conjugate: a virostatic agent against HIV-1.
(2016) In BioMetals 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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8821423
- author
- Gama, Ntombenhle ; Kumar, Kamlesh LU ; Ekengard, Erik LU ; Haukka, Matti ; Darkwa, James ; Nordlander, Ebbe LU and Meyer, Debra
- organization
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- subject
- in
- BioMetals
- volume
- 29
- issue
- 3
- pages
- 9 pages
- publisher
- Springer
- external identifiers
-
- pmid:26922346
- scopus:84971505201
- pmid:26922346
- 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
- 2016-04-01 14:09:21
- date last changed
- 2022-04-22 01:39:35
@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 < 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}}, 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}}, doi = {{10.1007/s10534-016-9921-9}}, volume = {{29}}, year = {{2016}}, }