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Evaluation of the in Vitro Antiretroviral Potential of Some Biginelli-Type Pyrimidines Publisher Pubmed



Zabihollahi R1 ; Vahabpour R2 ; Hartoonian C2 ; Sedaghati B3 ; Sadat SM2 ; Soleymani M4 ; Ranjbar M4 ; Fassihi A3 ; Aghasadeghi MR2 ; Memarian HR4 ; Salehi M1
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran
  3. 3. Department of Medicinal Chemistry, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Department of Chemistry, Faculty of Sciences, University of Isfahan, Isfahan, Iran

Source: Acta Virologica Published:2012


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 eff ect 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 (IC 50) of 100 nmol/l for inhibiting HIV-1 replication and 50% cytotoxic concentration (CC 50) 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 eff ects. 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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