Effects of Lipophilicity and Structural Features on the Antiherpes Activity of Digitalis Cardenolides and Derivatives.
antiherpes activity
antiviral agents, structure-activity relationship
cardenolides
in silico studies
log P
Journal
Chemistry & biodiversity
ISSN: 1612-1880
Titre abrégé: Chem Biodivers
Pays: Switzerland
ID NLM: 101197449
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
received:
28
04
2022
accepted:
06
09
2022
pubmed:
11
9
2022
medline:
22
10
2022
entrez:
10
9
2022
Statut:
ppublish
Résumé
There is growing interest in exploring Digitalis cardenolides as potential antiviral agents. Hence, we herein investigated the influence of structural features and lipophilicity on the antiherpes activity of 65 natural and semisynthetic cardenolides assayed in vitro against HSV-1. The presence of an α,β-unsaturated lactone ring at C-17, a β-hydroxy group at C-14 and C-3β-OR substituents were considered essential requirements for this biological activity. Glycosides were more active than their genins, especially monoglycosides containing a rhamnose residue. The activity enhanced in derivatives bearing an aldehyde group at C-19 instead of a methyl group, whereas inserting a C-5β-OH improved the antiherpes effect significantly. The cardenolides lipophilicity was accessed by measuring experimentally their log P values (n-octanol-water partition coefficient) and disclosed a range of lipophilicity (log P 0.75±0.25) associated with the optimal antiherpes activity. In silico studies were carried out and resulted in the establishment of two predictive models potentially useful to identify and/or optimize novel antiherpes cardenolides. The effectiveness of the models was confirmed by retrospective analysis of the studied compounds. This is the first SAR study addressing the antiherpes activity of cardenolides. The developed computational models were able to predict the active cardenolides and their log P values.
Identifiants
pubmed: 36085355
doi: 10.1002/cbdv.202200411
doi:
Substances chimiques
Cardenolides
0
1-Octanol
NV1779205D
Rhamnose
QN34XC755A
Plant Extracts
0
Antiviral Agents
0
Glycosides
0
Lactones
0
Aldehydes
0
Water
059QF0KO0R
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202200411Subventions
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico
ID : 490057/2011-0
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico
ID : 472544/2013-6
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico
ID : 305878/2016-6
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
ID : PNPD 2257/2011
Organisme : Fapemig
Organisme : APQ-00538-17
Organisme : IRSES/European Community
ID : 295251
Organisme : Hospital University of Tübingen
Informations de copyright
© 2022 The Authors. Chemistry & Biodiversity published by Wiley-VHCA AG, Zurich, Switzerland.
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