Plant extracts traditionally used for male impotence (Tribulus terrestris, Ferula hermonis, Epimedium breVicornum, Cinnamomum cassia), and the individual compounds cinnamaldehyde, ferutinin, and icariin, were screened against phosphodiesterase-5A1 (PDE5A1) activity. Human recombinant PDE5A1 was used as the enzyme source. Only E. breVicornum extract (80% inhibition at 50 μg/mL) and its active principle icariin (1) (IC50 5.9 μM) were active. To improve its inhibitory activity, 1 was subjected to various structural modifications. Thus, 3,7-bis(2-hydroxyethyl)icaritin (5), where both sugars in 1 were replaced with hydroxyethyl residues, potently inhibited PDE5A1 with an IC50 very close to that of sildenafil (IC50 75 vs 74 nM). Thus, 5 was 80 times more potent than 1, and its selectivity versus phosphodiesterase-6 (PDE6) and cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) was much higher in comparison with sildenafil. The improved pharmacodynamic profile and lack of cytotoxicity on human fibroblasts make compound 5 a promising candidate for further development.

Dell’Agli M., Galli G., Dal Cero E., Belluti F., Matera R., Zironi E., et al. (2008). Potent inhibition of human phosphodiesterase-5 by icariin derivatives. JOURNAL OF NATURAL PRODUCTS, 71, 1513-1517 [10.1021/np800049y].

Potent inhibition of human phosphodiesterase-5 by icariin derivatives

BELLUTI, FEDERICA;MATERA, RICCARDO;ZIRONI, ELISA;PAGLIUCA, GIAMPIERO;
2008

Abstract

Plant extracts traditionally used for male impotence (Tribulus terrestris, Ferula hermonis, Epimedium breVicornum, Cinnamomum cassia), and the individual compounds cinnamaldehyde, ferutinin, and icariin, were screened against phosphodiesterase-5A1 (PDE5A1) activity. Human recombinant PDE5A1 was used as the enzyme source. Only E. breVicornum extract (80% inhibition at 50 μg/mL) and its active principle icariin (1) (IC50 5.9 μM) were active. To improve its inhibitory activity, 1 was subjected to various structural modifications. Thus, 3,7-bis(2-hydroxyethyl)icaritin (5), where both sugars in 1 were replaced with hydroxyethyl residues, potently inhibited PDE5A1 with an IC50 very close to that of sildenafil (IC50 75 vs 74 nM). Thus, 5 was 80 times more potent than 1, and its selectivity versus phosphodiesterase-6 (PDE6) and cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) was much higher in comparison with sildenafil. The improved pharmacodynamic profile and lack of cytotoxicity on human fibroblasts make compound 5 a promising candidate for further development.
2008
Dell’Agli M., Galli G., Dal Cero E., Belluti F., Matera R., Zironi E., et al. (2008). Potent inhibition of human phosphodiesterase-5 by icariin derivatives. JOURNAL OF NATURAL PRODUCTS, 71, 1513-1517 [10.1021/np800049y].
Dell’Agli M.; Galli G.; Dal Cero E.; Belluti F.; Matera R.; Zironi E.; Pagliuca G.; Bosisio E.
File in questo prodotto:
Eventuali allegati, non sono esposti

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/62682
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 34
  • Scopus 129
  • ???jsp.display-item.citation.isi??? 106
social impact