Abstract |
Despite the success of highly active antiretroviral therapy, AIDS still remains as one of the most important world health problems. Toxicity of current available drugs and inevitable emergence of multi- drug resistant strains makes things worse. In the present study a series of novel Biginelli-type pyrimidine compounds were evaluated as potential anti-human immunodeficiency virus (HIV)-1 agents using green fluorescence protein (GFP) reporter single round HIV-1 infection assay. The rate of infected cells was monitored by flowcytometry. The effect of compounds on the cellular proliferation was considered as the cyotoxicity. The anti-HIV-1 active compounds were selected for HIV-1 replication and syncytium formation assays. The antiretroviral activity of compounds was measured against luciferase reporter A murine leukemia virus (AMLV) virions as the retrovirus control. Compounds 2, 5, 6, 8, 11, 12, 13, 17, 18, 20, and 21 were the most potent against HIV-1. Compound 8 had the 50% inhibitory concentration (IC50) of 100 nmol/l for inhibiting HIV-1 replication and 50% cytotoxic concentration (CC50) was up to 100 μmol/l (therapeutic index (TI) >1000). Results show that the active compounds were able to inhibit the retrovirus control as well. Analysis of structure of the studied compounds proved relationships with their anti-HIV-1 effects. Some of the studied compounds seem to be promising anti-HIV-1 drug candidates. Structural manipulation based on the well-defined structure-activity relationships might propose some new leads for anti-HIV-1 drug discovery programs.
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Authors | R Zabihollahi, R Vahabpour, C Hartoonian, B Sedaghati, S M Sadat, M Soleymani, M Ranjbar, A Fassihi, M R Aghasadeghi, H R Memarian, M Salehi |
Journal | Acta virologica
(Acta Virol)
Vol. 56
Issue 1
Pg. 11-8
( 2012)
ISSN: 0001-723X [Print] Slovakia |
PMID | 22404604
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-HIV Agents
- Pyrimidines
- Green Fluorescent Proteins
- Luciferases
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Topics |
- Acquired Immunodeficiency Syndrome
(drug therapy, virology)
- Animals
- Anti-HIV Agents
(chemical synthesis, pharmacology)
- Cell Line
- Cell Survival
(drug effects)
- Dogs
- Genes, Reporter
- Giant Cells
(drug effects, physiology)
- Green Fluorescent Proteins
(genetics)
- HIV-1
(drug effects, growth & development)
- Humans
- Inhibitory Concentration 50
- Luciferases
(genetics)
- Pyrimidines
(chemical synthesis, pharmacology)
- Structure-Activity Relationship
- T-Lymphocytes
(drug effects, virology)
- Thymocytes
(drug effects, virology)
- Virus Replication
(drug effects)
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