Acetylsalicylic acid (ASA) is the most widely used drug for the prevention of thrombotic risk in the heart, brain and peripheral circulation. Different reports suggest that vitamin E decreases neuronal cell death caused by ischemia and reperfusion in rat models, and influences in vitro antiplatelet effect of aspirin. Unfortunately, ASA causes gastrointestinal side effects, due to its irreversible inhibition of the COX-1 in stomach. Moreover, the gastric side effect seems to involve an oxidative stress. For this reasons, the coadministration of vitamin E and ASA has been proposed to reduces the gastric injury determined by aspirin. Starting from these data, our study focused on providing multifunctional codrugs obtained joining ASA to tocopherols to take advantage of the synergistic mechanisms regarding the antithrombotic activity of both compounds. In addition, we exploited the protecting role of Vitamin E against gastric side effects of ASA. In the present paper, we reported the synthesis and the in vitro hydrolysis of two codrug esters of ASA with alpha- and gamma-tocopherols. We also investigated the oral pharmacokinetic in rabbit and probed the preliminary pharmacological evaluation in rat. The synthesized codrugs exhibited anti-inflammatory activity with a strong and significant reduction in gastrolesivity.

Design, Synthesis and Antiinflammatory Activity of Novel g-Tocopherol Acetylsalicylic acid Ester Codrug

SPADARO A;RONSISVALLE G;PAPPALARDO M;Bucolo C
2010

Abstract

Acetylsalicylic acid (ASA) is the most widely used drug for the prevention of thrombotic risk in the heart, brain and peripheral circulation. Different reports suggest that vitamin E decreases neuronal cell death caused by ischemia and reperfusion in rat models, and influences in vitro antiplatelet effect of aspirin. Unfortunately, ASA causes gastrointestinal side effects, due to its irreversible inhibition of the COX-1 in stomach. Moreover, the gastric side effect seems to involve an oxidative stress. For this reasons, the coadministration of vitamin E and ASA has been proposed to reduces the gastric injury determined by aspirin. Starting from these data, our study focused on providing multifunctional codrugs obtained joining ASA to tocopherols to take advantage of the synergistic mechanisms regarding the antithrombotic activity of both compounds. In addition, we exploited the protecting role of Vitamin E against gastric side effects of ASA. In the present paper, we reported the synthesis and the in vitro hydrolysis of two codrug esters of ASA with alpha- and gamma-tocopherols. We also investigated the oral pharmacokinetic in rabbit and probed the preliminary pharmacological evaluation in rat. The synthesized codrugs exhibited anti-inflammatory activity with a strong and significant reduction in gastrolesivity.
acetylsalycilic acid; antinflammatory activity; codrug; gamma-tocopherol; gastrolesivity; rabbit; rat
File in questo prodotto:
Non ci sono file associati a questo prodotto.

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/20.500.11769/26877
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 10
  • ???jsp.display-item.citation.isi??? ND
social impact