A small library of arylthioamides 1–12 was easily synthesized, and their H2S-releasing properties were evaluated both in the absence or in the presence of an organic thiol such as l-cysteine. A number of arylthioamides (1–3 and 7) showed a slow and l-cysteine-dependent H2S-releasing mechanism, similar to that exhibited by the reference slow H2S-releasing agents, such as diallyl disulfide (DADS) and the phosphinodithioate derivative GYY 4137. Compound 1 strongly abolished the noradrenaline-induced vasoconstriction in isolated rat aortic rings and hyperpolarized the membranes of human vascular smooth muscle cells in a concentration-dependent fashion. Finally, a significant reduction of the systolic blood pressure of anesthetized normotensive rats was observed after its oral administration. Altogether these results highlighted the potential of arylthioamides 1–3 and 7 as H2S-donors for basic studies, and for the rational design/development of promising pharmacotherapeutic agents to treat cardiovascular diseases.

Arylthioamides as H2S Donors:l-Cysteine-Activated Releasing Properties and Vascular Effects in Vitro and in Vivo

MARTELLI, ALMA;TESTAI, LARA;Citi, Valentina;MARINO, ALICE;BARRESI, ELISABETTA;NESI, GIULIA;RAPPOSELLI, SIMONA;TALIANI, SABRINA;DA SETTIMO PASSETTI, FEDERICO;BRESCHI, MARIA CRISTINA;CALDERONE, VINCENZO
2013

Abstract

A small library of arylthioamides 1–12 was easily synthesized, and their H2S-releasing properties were evaluated both in the absence or in the presence of an organic thiol such as l-cysteine. A number of arylthioamides (1–3 and 7) showed a slow and l-cysteine-dependent H2S-releasing mechanism, similar to that exhibited by the reference slow H2S-releasing agents, such as diallyl disulfide (DADS) and the phosphinodithioate derivative GYY 4137. Compound 1 strongly abolished the noradrenaline-induced vasoconstriction in isolated rat aortic rings and hyperpolarized the membranes of human vascular smooth muscle cells in a concentration-dependent fashion. Finally, a significant reduction of the systolic blood pressure of anesthetized normotensive rats was observed after its oral administration. Altogether these results highlighted the potential of arylthioamides 1–3 and 7 as H2S-donors for basic studies, and for the rational design/development of promising pharmacotherapeutic agents to treat cardiovascular diseases.
Martelli, Alma; Testai, Lara; Citi, Valentina; Marino, Alice; Pugliesi, Isabella; Barresi, Elisabetta; Nesi, Giulia; Rapposelli, Simona; Taliani, Sabrina; DA SETTIMO PASSETTI, Federico; Breschi, MARIA CRISTINA; Calderone, Vincenzo
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/274735
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