Arylthioamides as H2S Donors: l-Cysteine-Activated Releasing Properties and Vascular Effects in Vitro and in Vivo.
(2013) ACS Medicinal Chemistry Letters — Vol. 4, n° 10, p. 904-908 (2013)
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- 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.
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Martelli, A., Testai, L., Citi, V., Marino, A., Pugliesi, I., Barresi, E., Nesi, G., Rapposelli, S., Taliani, S., Da Settimo, F., Breschi, M. C., & Calderone, V. (2013). Arylthioamides as H2S Donors: l-Cysteine-Activated Releasing Properties and Vascular Effects in Vitro and in Vivo. ACS Medicinal Chemistry Letters, 4(10), 904-908. https://doi.org/10.1021/ml400239a (Original work published 2013)