title: Synthesis, HIV-RT inhibitory activity and SAR of 1-benzyl-1H-1,2,3-triazole derivatives of carbohydrates.
abstract: This paper describes the synthesis of several 1-benzyl-1H-1,2,3-triazoles attached to different carbohydrate templates and their in vitro inhibitory profile against HIV-1 reverse transcriptase. In addition a theoretical comparison of the most active compounds with other classical antivirals was also performed. Our results showed 2a, 2d and 2g as the most active compounds that inhibited the HIV-1 reverse transcriptase catalytic activity with cytotoxicity lower than AZT and SI higher than DDC and DDI. The overall theoretical analysis of the molecular descriptors of 2a, 2d and 2g revealed that their HOMO energy is similar to other antivirals in use (AZT, DDC, DDI and 3TC) and together with the volume may contribute for the biological profile as they may allow new interactions with the target. In fact the 1,2,3-triazole compounds presented more lipophilicity and higher molecular volume and weight than the antivirals studied, which suggested that these features might not only contribute for new interactions with the HIV-RT but also influence the specificity and consequently the low cytoxicity profile of these compounds. Thus these data point them as promising leading compounds for generating new anti-HIV-RT compounds.
authors.affiliation: Universidade Federal Fluminense, Departamento de Química Orgânica, Instituto de Química, Outeiro de São João Baptista, CEP 24020-141, Niterói, RJ, Brazil.
authors.forename: Fernando de C
authors.initials: Fde C
authors.lastname: da Silva
authors.forename: Maria Cecilia B V
authors.initials: MC
authors.lastname: de Souza
authors.forename: Izabel I P
authors.initials: II
authors.lastname: Frugulhetti
authors.forename: Helena C
authors.initials: HC
authors.lastname: Castro
authors.forename: Silmara L de O
authors.initials: SL
authors.lastname: Souza
authors.forename: Thiago Moreno L
authors.initials: TM
authors.lastname: de Souza
authors.forename: Diego Q
authors.initials: DQ
authors.lastname: Rodrigues
authors.forename: Alessandra M T
authors.initials: AM
authors.lastname: Souza
authors.forename: Paula A
authors.initials: PA
authors.lastname: Abreu
authors.forename: Fabiana
authors.initials: F
authors.lastname: Passamani
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Rodrigues
authors.forename: Vitor F
authors.initials: VF
authors.lastname: Ferreira
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002241:Carbohydrates / Q000138:chemical synthesis* / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D002241:Carbohydrates; D018894:Reverse Transcriptase Inhibitors; D014230:Triazoles; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase