title: Design, synthesis, and anti-HIV-1 activity of 1-substituted 3-(3,5-dimethylbenzyl)triazine derivatives.
abstract: BACKGROUND
  The reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is an attractive target for the development of drugs used in the treatment of HIV-1 infection and acquired immune deficiency syndrome (AIDS). We have continued the search for novel anti-HIV-1 agents using the structure-activity relationships of the successful 1,3-disubstituted and 1,3,6-trisubstituted uracil-type HIV-1 RT inhibitors.
  
  
  METHODS
  A series of new triazine analogs were synthesized using an established method. The anti-HIV-1 activities of these compounds were determined based on the inhibition of virus-induced cytopathogenicity in MT-4 cells. The cytotoxicity of the compounds was evaluated by assessing the viability of mock-infected cells.
  
  
  RESULTS
  Some of the compounds showed good-to-moderate activities against HIV-1, with half-maximal effective concentrations (EC50) in the submicromolar range. In particular, a dihydro-1-(4-aminobenzyl)triazine analog showed satisfactory anti-HIV-1 activity with an EC50 of 0.110 µM and a selectivity index (SI) of 909. Furthermore, molecular modeling analyses were performed to explore the major interactions between HIV-1 RT and potent inhibitors. These results may be important for further development of this class of compounds as anti-HIV-1 agents.
  
  
  CONCLUSIONS
  The satisfactory anti-HIV-1 activity of triazine analogs may serve as the basis for further investigations of the behavior of this class of compounds against drug-resistant mutants.
authors.affiliation: Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Sanuki City, Kagawa, Japan bara@kph.bunri-u.ac.jp.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Sakakibara
authors.affiliation: Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Balboni
authors.affiliation: Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Cenzo
authors.initials: C
authors.lastname: Congiu
authors.affiliation: Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Onnis
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, Setagaya, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Demizu
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, Setagaya, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Misawa
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, Setagaya, Tokyo, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kurihara
authors.affiliation: Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Sanuki City, Kagawa, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Sanuki City, Kagawa, Japan.
authors.forename: Tokumi
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toyama
authors.affiliation: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D014227:Triazines
keywords: AIDS; HIV; non-nucleoside reverse transcriptase inhibitors