Modeling and spectroscopic studies of synthetic diazabicyclo analogs of the HIV-1 inhibitor BMS-378806 and evaluation of their antiviral activity

Laura Legnani, Diego Colombo, Elena Cocchi, Lucrezia Solano, Stefania Villa, Lucia Lopalco, Valeria Asti, Lorenzo Diomede, Franca Marinone Albini, Lucio Toma

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Three diazabicyclo analogs of BMS-378806, in which theaxial methyl group present on its piperazine ring is replaced by a carbon bridge, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane and-nonane derivatives maintained a significant infectivity reduction power, whereas the diazabicycloheptane derivative was much less effective. A modeling study allowed to relate the antiviral activity to the conformational preferences of the compounds. Moreover, similarly to BMS-378806, theoretical calculations predict the existence of different conformational families corresponding to the possible arrangements at the two planar amido functions of the compounds. High-field 1H NMR spectra confirm these results, as they show two distinct series of signals. A viral neutralization assay on a panel of six HIV-related pseudoviruses allowed the determination of the antiviral activity of three diazabicyclo analogs of BMS-378806, in which the axial methyl group on its piperazine ring is replaced by a carbon bridge. The diazabicyclooctane and-nonane derivatives show a significant infectivity reduction power that is related to their conformational preference.

Original languageEnglish
Pages (from-to)287-294
Number of pages8
JournalEuropean Journal of Organic Chemistry
Issue number2
DOIs
Publication statusPublished - Jan 2011

Fingerprint

nonanes
human immunodeficiency virus
inhibitors
Antiviral Agents
analogs
Derivatives
evaluation
carbon
rings
Assays
Carbon
nuclear magnetic resonance
Nuclear magnetic resonance
BMS-378806
nonane
piperazine

Keywords

  • Antiviral agents
  • Inhibitors
  • Molecular modeling
  • NMR spectroscopy

ASJC Scopus subject areas

  • Organic Chemistry
  • Physical and Theoretical Chemistry

Cite this

Modeling and spectroscopic studies of synthetic diazabicyclo analogs of the HIV-1 inhibitor BMS-378806 and evaluation of their antiviral activity. / Legnani, Laura; Colombo, Diego; Cocchi, Elena; Solano, Lucrezia; Villa, Stefania; Lopalco, Lucia; Asti, Valeria; Diomede, Lorenzo; Marinone Albini, Franca; Toma, Lucio.

In: European Journal of Organic Chemistry, No. 2, 01.2011, p. 287-294.

Research output: Contribution to journalArticle

Legnani, Laura ; Colombo, Diego ; Cocchi, Elena ; Solano, Lucrezia ; Villa, Stefania ; Lopalco, Lucia ; Asti, Valeria ; Diomede, Lorenzo ; Marinone Albini, Franca ; Toma, Lucio. / Modeling and spectroscopic studies of synthetic diazabicyclo analogs of the HIV-1 inhibitor BMS-378806 and evaluation of their antiviral activity. In: European Journal of Organic Chemistry. 2011 ; No. 2. pp. 287-294.
@article{d87490c68a37440a99ab259adf8ecf30,
title = "Modeling and spectroscopic studies of synthetic diazabicyclo analogs of the HIV-1 inhibitor BMS-378806 and evaluation of their antiviral activity",
abstract = "Three diazabicyclo analogs of BMS-378806, in which theaxial methyl group present on its piperazine ring is replaced by a carbon bridge, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane and-nonane derivatives maintained a significant infectivity reduction power, whereas the diazabicycloheptane derivative was much less effective. A modeling study allowed to relate the antiviral activity to the conformational preferences of the compounds. Moreover, similarly to BMS-378806, theoretical calculations predict the existence of different conformational families corresponding to the possible arrangements at the two planar amido functions of the compounds. High-field 1H NMR spectra confirm these results, as they show two distinct series of signals. A viral neutralization assay on a panel of six HIV-related pseudoviruses allowed the determination of the antiviral activity of three diazabicyclo analogs of BMS-378806, in which the axial methyl group on its piperazine ring is replaced by a carbon bridge. The diazabicyclooctane and-nonane derivatives show a significant infectivity reduction power that is related to their conformational preference.",
keywords = "Antiviral agents, Inhibitors, Molecular modeling, NMR spectroscopy",
author = "Laura Legnani and Diego Colombo and Elena Cocchi and Lucrezia Solano and Stefania Villa and Lucia Lopalco and Valeria Asti and Lorenzo Diomede and {Marinone Albini}, Franca and Lucio Toma",
year = "2011",
month = "1",
doi = "10.1002/ejoc.201001073",
language = "English",
pages = "287--294",
journal = "Annalen der Pharmacie",
issn = "0075-4617",
publisher = "Wiley-VCH Verlag",
number = "2",

}

TY - JOUR

T1 - Modeling and spectroscopic studies of synthetic diazabicyclo analogs of the HIV-1 inhibitor BMS-378806 and evaluation of their antiviral activity

AU - Legnani, Laura

AU - Colombo, Diego

AU - Cocchi, Elena

AU - Solano, Lucrezia

AU - Villa, Stefania

AU - Lopalco, Lucia

AU - Asti, Valeria

AU - Diomede, Lorenzo

AU - Marinone Albini, Franca

AU - Toma, Lucio

PY - 2011/1

Y1 - 2011/1

N2 - Three diazabicyclo analogs of BMS-378806, in which theaxial methyl group present on its piperazine ring is replaced by a carbon bridge, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane and-nonane derivatives maintained a significant infectivity reduction power, whereas the diazabicycloheptane derivative was much less effective. A modeling study allowed to relate the antiviral activity to the conformational preferences of the compounds. Moreover, similarly to BMS-378806, theoretical calculations predict the existence of different conformational families corresponding to the possible arrangements at the two planar amido functions of the compounds. High-field 1H NMR spectra confirm these results, as they show two distinct series of signals. A viral neutralization assay on a panel of six HIV-related pseudoviruses allowed the determination of the antiviral activity of three diazabicyclo analogs of BMS-378806, in which the axial methyl group on its piperazine ring is replaced by a carbon bridge. The diazabicyclooctane and-nonane derivatives show a significant infectivity reduction power that is related to their conformational preference.

AB - Three diazabicyclo analogs of BMS-378806, in which theaxial methyl group present on its piperazine ring is replaced by a carbon bridge, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane and-nonane derivatives maintained a significant infectivity reduction power, whereas the diazabicycloheptane derivative was much less effective. A modeling study allowed to relate the antiviral activity to the conformational preferences of the compounds. Moreover, similarly to BMS-378806, theoretical calculations predict the existence of different conformational families corresponding to the possible arrangements at the two planar amido functions of the compounds. High-field 1H NMR spectra confirm these results, as they show two distinct series of signals. A viral neutralization assay on a panel of six HIV-related pseudoviruses allowed the determination of the antiviral activity of three diazabicyclo analogs of BMS-378806, in which the axial methyl group on its piperazine ring is replaced by a carbon bridge. The diazabicyclooctane and-nonane derivatives show a significant infectivity reduction power that is related to their conformational preference.

KW - Antiviral agents

KW - Inhibitors

KW - Molecular modeling

KW - NMR spectroscopy

UR - http://www.scopus.com/inward/record.url?scp=78650876015&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650876015&partnerID=8YFLogxK

U2 - 10.1002/ejoc.201001073

DO - 10.1002/ejoc.201001073

M3 - Article

SP - 287

EP - 294

JO - Annalen der Pharmacie

JF - Annalen der Pharmacie

SN - 0075-4617

IS - 2

ER -