ascorbic-acid and indoxyl

A family of 12 members of Naphthalene-2-ol-indolin-2-one-thiocarbamides (5a-l) with pharmacological potentials of cardiovascular modulator were efficiently synthesized and evaluated. These compounds show inhibitory activity on angiotensin-converting enzyme (ACE), which is a principal constituent of the renin-angiotensin system and causative source for hypertension (HTN) (elevated blood pressure) and congestive heart failure (CHF), a parameter that was tested in this report. Prior to this, to get more insight into the binding mode and inhibition of human ACE C-domain (PDB ID: 2XY9) and N-domain (PDB ID: 3NXQ) compounds 5a-l was docked into the active site of them. The established inhibitory constant (Ki) (range 40-500 nM) and least binding affinities (-18.52 to -30.57 kcal/mol) indicated the therapeutic selectivity of compounds 5a-l towards ACE C-domain inhibition over ACE N-domain. The cytotoxicity effect of most potent compounds among 5a-l were tested in normal breast cells and MCF-7 cell lines. Simultaneously, H

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Heart Failure; Humans; Hypertension; Indoles; Models, Molecular; Molecular Structure; Structure-Activity Relationship; Thrombolytic Therapy

It is reported (J. B. S. Shear, C. Xu and W. W. Webb, Photochem. Photobiol. 1997, 65, 931) that multiphoton near infrared excitation of 5-hydroxytryptophan results in a transient product with green fluorescence. Visible fluorescence from multiphoton excitation enables detection of 5-hydroxytryptophan with extremely high sensitivity and also has potential applications in imaging of biological systems and investigation of protein dynamics. The characteristic fluorescence at 500 nm has now also been observed in a two laser experiment whereby 308 nm photolysis of the solution is followed by an excitation step at 430 nm. Fluorescence was observed in aerated and deaerated solutions and in the presence of ascorbate. Enhancement of fluorescence was observed on addition of ethanol. Transient absorption experiments with 308 nm photolysis showed the formation of three transient species. In the presence of ascorbate the radical formed by photoionisation was quenched, revealing a long-lived species (tau > 1 ms) with a similar absorption spectrum, which is ascribed to the fluorescing species. Fluorescence induced by multiphoton excitation had a lifetime of 910 +/- 10 ps and was also unaffected by ascorbate. In the presence of organic solvents there was an increase in fluorescence lifetime, but a decrease in overall fluorescence intensity. The fluorescence intensity and fluorescence lifetime both decreased in acidic solution (pH < 3). The results indicate that the fluorescence does not originate from the 5-indoxyl radical as previously suggested but from one or more other transient products which require further characterisation.

Topics: 5-Hydroxytryptophan; Ascorbic Acid; Fluorescence; Indoles; Kinetics; Lasers; Photolysis; Photons; Solutions; Solvents; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet