Synthesis, HIV-RT inhibitory activity and SAR of 1-benzyl-1H-1,2,3-triazole derivatives of carbohydrates.
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.
da Silva
Fernando de C
Fde C
Universidade Federal Fluminense, Departamento de Química Orgânica, Instituto de Química, Outeiro de São João Baptista, CEP 24020-141, Niterói, RJ, Brazil.
de Souza
Maria Cecilia B V
MC
Frugulhetti
Izabel I P
II
Castro
Helena C
HC
Souza
Silmara L de O
SL
de Souza
Thiago Moreno L
TM
Rodrigues
Diego Q
DQ
Souza
Alessandra M T
AM
Abreu
Paula A
PA
Passamani
Fabiana
F
Rodrigues
Carlos R
CR
Ferreira
Vitor F
VF
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
D019380:Anti-HIV Agents; D002241:Carbohydrates; D018894:Reverse Transcriptase Inhibitors; D014230:Triazoles; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase