title: Evaluation of the in vitro antiretroviral potential of some  Biginelli-type pyrimidines.
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.
authors.affiliation: Department of Medical Genetics, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: R
authors.initials: R
authors.lastname: Zabihollahi
authors.forename: R
authors.initials: R
authors.lastname: Vahabpour
authors.forename: C
authors.initials: C
authors.lastname: Hartoonian
authors.forename: B
authors.initials: B
authors.lastname: Sedaghati
authors.forename: S M
authors.initials: SM
authors.lastname: Sadat
authors.forename: M
authors.initials: M
authors.lastname: Soleymani
authors.forename: M
authors.initials: M
authors.lastname: Ranjbar
authors.forename: A
authors.initials: A
authors.lastname: Fassihi
authors.forename: M R
authors.initials: MR
authors.lastname: Aghasadeghi
authors.forename: H R
authors.initials: HR
authors.lastname: Memarian
authors.forename: M
authors.initials: M
authors.lastname: Salehi
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000821:virology; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D017930:Genes, Reporter; D015726:Giant Cells / Q000187:drug effects* / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D020128:Inhibitory Concentration 50; D008156:Luciferases / Q000235:genetics; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology; D060168:Thymocytes / Q000187:drug effects / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D011743:Pyrimidines; D049452:Green Fluorescent Proteins; D008156:Luciferases