Potential anti-herpes and cytotoxic action of novel semisynthetic digitoxigenin-derivatives

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autorinnen und Autoren: Boff L, Munkert J, Ottoni FM, Schneider NFZ, Ramos GS, Kreis W, Andrade SF, De Souza Filho JD, Braga FC, Alves RJ, De Padua RM, Simões CMO
Zeitschrift: European Journal of Medicinal Chemistry
Jahr der Veröffentlichung: 2019
Band: 167
Seitenbereich: 546-561
ISSN: 0223-5234
Sprache: Englisch


Abstract

In recent years, new therapeutic possibilities were proposed for cardiac glycosides traditionally used to treat heart diseases, such as anticancer and antiviral activities. In this sense, this work aimed to synthesize the readily accessible 3β-azido-3-deoxydigitoxigenin (5) from digitoxigenin (1). Two new series of compounds were obtained from derivative (5): (i) O-glycosyl trizols through click chemistry with propargyl glycosides; and (ii) compounds substituted in the alpha carbonyl position with different residues linked via an amino-group. All obtained derivatives have their chemical structures confirmed, and their anti-herpes (against HSV-types 1 and 2 replication) and cytotoxic (against PC3, A549, HCT-8 and LNCaP cell lines) activities evaluated. Compounds 10 and 11 exhibited the most promising results against HSV-1 (KOS and 29-R strains) and HSV-2 (333 strain) replication with SI values > 1000.
Both compounds were also the most cytotoxic for the human cancer cell lines tested with IC50 values similar to those of paclitaxel. They also presented reduced toxicity toward non-cancerous cell lines (MRC-5 and HGF cells). Promising compounds were tested in regard to their ability to inhibit Na+/K+-ATPase. The inhibition rate correlates suitably with the bioactivity demonstrated by those both compounds against the different human cancer cells tested as well as against HSV replication. Moreover, the results showed that specific chemical features of compound 10 and 11 influenced the bioactivities tested. In summary, it was possible to obtain novel digitoxigenin-derivatives with remarkable cytotoxic and anti-herpes activities as well as low toxicity and high selectivity. In this way, they could be considered potential molecules for the development of new drugs.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Kreis, Wolfgang Prof. Dr.
Lehrstuhl für Pharmazeutische Biologie
Munkert, Jennifer Dr.
Lehrstuhl für Pharmazeutische Biologie


Einrichtungen weiterer Autorinnen und Autoren

Federal University of Santa Catarina / Universidade Federal de Santa Catarina (UFSC)
Universidade Federal de Minas Gerais (UFMG)
Universidade Federal do Rio Grande do Sul (UFRGS)


Zitierweisen

APA:
Boff, L., Munkert, J., Ottoni, F.M., Schneider, N.F.Z., Ramos, G.S., Kreis, W.,... Simões, C.M.O. (2019). Potential anti-herpes and cytotoxic action of novel semisynthetic digitoxigenin-derivatives. European Journal of Medicinal Chemistry, 167, 546-561. https://dx.doi.org/10.1016/j.ejmech.2019.01.076

MLA:
Boff, Laurita, et al. "Potential anti-herpes and cytotoxic action of novel semisynthetic digitoxigenin-derivatives." European Journal of Medicinal Chemistry 167 (2019): 546-561.

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Zuletzt aktualisiert 2019-04-06 um 14:07