title: Arylthioamides as H2S Donors: l-Cysteine-Activated Releasing Properties and Vascular Effects in Vitro and in Vivo.
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.
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , via Bonanno, 6, I-56126 Pisa, Italy.
authors.forename: Alma
authors.initials: A
authors.lastname: Martelli
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , via Bonanno, 6, I-56126 Pisa, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Testai
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , via Bonanno, 6, I-56126 Pisa, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Citi
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , via Bonanno, 6, I-56126 Pisa, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Marino
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , via Bonanno, 6, I-56126 Pisa, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Pugliesi
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , via Bonanno, 6, I-56126 Pisa, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Barresi
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , via Bonanno, 6, I-56126 Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Nesi
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , via Bonanno, 6, I-56126 Pisa, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Rapposelli
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , via Bonanno, 6, I-56126 Pisa, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Taliani
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , via Bonanno, 6, I-56126 Pisa, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Da Settimo
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , via Bonanno, 6, I-56126 Pisa, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Breschi
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , via Bonanno, 6, I-56126 Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Calderone
keywords: H2S-releasing drugs; Hydrogen sulphide; cardiovascular system; hybrid drugs; hypertension; potassium channels; thioamide; vascular smooth muscle