Vasodilatory Activity of Novel Carbamate Derivatives of Isatin

Abstract

Isatin (1H-indole-2,3 dione) is an endogenous compound that may act as a physiological regulator of muscle contraction by reducing cGMP production by inhibition of guanylyl cyclase (GC) activity. Intracellular cGMP levels can regulate the contractile response of smooth muscle. Therefore, in the present study we investigated the effects of seven novel carbamate derivatives of isatin, namely C1-C7, on the contractility of aortic rings from Wistar rats. Carbamates C1 and C6 most effectively promoted endothelium-dependent relaxation of aortic rings pretreated with 10 micromol/L phenylephrine (PE) to induce contraction. The concentration of the C1 and C6 carbamates necessary to reduce PE-induced aortic contraction by 50% (IC(50)) was 5.6 +/- 1.0 and 48.4 +/- 3.4 micromol/L, respectively. Carbamate derivative-induced vasodilation required an intact endothelium, which is responsible for nitric oxide (NO) release. Pretreatment of rings with 100 micromol/L naloxone or 10 micromol/L atropine prevented the C1- and C6-mediated vascular relaxation, indicating that the vasodilatory activity was dependent on the activation of opioid or muscarinic receptors, respectively. The results of our studies provide insights into the role of novel carbamates in the regulation of vascular tone. Carbamates could stimulate NO synthesis, which induces vasodilation primarily by stimulation of GC and cGMP production. Taken together, our findings suggest that carbamate derivative-induced vasodilation may be considered an alternative treatment for primary and/or secondary hypertension.

Acylideneoxoindoles: A new class of reversible inhibitors of human transglutaminase 2

“…Acylidene oxoindoles have also shown biological activity, for example, as kinase inhibitors,35,36 phosphatase inhibitors,37 promoters of vasodilatation,38 antifungal agents,39 and activators of TRP1 ion channels 40. As described in this communication, we have identified in 3-acylidene-2-oxoindoles a new class of reversible inhibitors of human TG2.…”

The Isatins of Professor Angelo

“…Muitos produtos destas reações foram ensaiados por seus colaboradores para diversas atividades biológicas. [1][2][3][4] Com as isatinas, o professor Angelo ganhou prêmios, alcançou certa liderança nacional e internacional, e ocupou as principais posições em rankings de publicações no Brasil.…”

“…35 Derivados da convolutamidina A foram substratos para a síntese de triptofóis 135, estes possuem um esqueleto indólico e uma cadeia lateral hidroxietila ligada ao carbono 3 que pode aprese tar α-e/ou β-substituintes. A síntese dos triptofóis foi realizada a partir da redução com solução de BH 3 .THF (Esquema 28). 36 Um mecanismo simplificado de reação para a obtenção de triptofóis pela redução de adutos aldólicos de isatinas com BH 3 .THF pode ser visto no Esquema 29.…”

“…A síntese dos triptofóis foi realizada a partir da redução com solução de BH 3 .THF (Esquema 28). 36 Um mecanismo simplificado de reação para a obtenção de triptofóis pela redução de adutos aldólicos de isatinas com BH 3 .THF pode ser visto no Esquema 29. 36 Rev.…”

Isatin Analysis Using Flow Injection Analysis with Amperometric Detection – Comparison of Tetrahedral Amorphous Carbon and Diamond Electrode Performance

“…They are made up of a two‐ring (bicyclic) structure containing a six‐carbon (benzene) ring fused to a five membered nitrogen‐containing ring (pyrrole). Isatin (Figure below) is an indole found endogenously in humans and rodents . It is a modulator of different biochemical processes and a neurochemical regulator in the brain.…”