Effects of Lipophilicity and Structural Features on the Antiherpes Activity of Digitalis Cardenolides and Derivatives
De Padua RM, Kratz JM, Munkert J, Bertol JW, Rigotto C, Schuster D, Maltarollo VG, Kreis W, Oliveira Simoes CM, Braga FC (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Abstract
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.
Authors with CRIS profile
Jennifer Munkert
Lehrstuhl für Pharmazeutische Biologie
Wolfgang Kreis
Lehrstuhl für Pharmazeutische Biologie
Involved external institutions
Federal University of Santa Catarina / Universidade Federal de Santa Catarina (UFSC)
Brazil (BR)
Universidade Federal de Minas Gerais (UFMG)
Brazil (BR)
Paracelsus Medizinische Privatuniversität
Austria (AT)
Brazil (BR)
Universidade Federal de Minas Gerais (UFMG)
Brazil (BR)
Paracelsus Medizinische Privatuniversität
Austria (AT)
How to cite
APA:
De Padua, R.M., Kratz, J.M., Munkert, J., Bertol, J.W., Rigotto, C., Schuster, D.,... Braga, F.C. (2022). Effects of Lipophilicity and Structural Features on the Antiherpes Activity of Digitalis Cardenolides and Derivatives. Chemistry & Biodiversity. https://dx.doi.org/10.1002/cbdv.202200411
MLA:
De Padua, Rodrigo Maia, et al. "Effects of Lipophilicity and Structural Features on the Antiherpes Activity of Digitalis Cardenolides and Derivatives." Chemistry & Biodiversity (2022).
BibTeX: Download