Experimental and theoretical investigations of four amine derivatives as effective corrosion inhibitors for mild steel in HCl medium.

Four amine derivative compounds were synthesized: 2-[(phenylamino)methyl]phenol, 2-{[(4-hydroxyphenyl)amino]methyl}phenol, 2-[(2-hydroxybenzyl)amino]benzonitrile and 2-{[(3-chlorophenyl)amino]methyl}phenol. The structure of the organic molecules was confirmed by FT-IR, 13C NMR and 1H NMR spectroscopy analyses. Their corrosion inhibition performances on mild steel in 1 M HCl were investigated using electrochemical measurements and surface analysis. Scanning electron microscopy analysis confirms the presence on the mild steel surface of a protective film of the as-prepared organic compounds, which depends on the substituent groups. Moreover, density functional theory and molecular dynamics simulation were employed in order to determine the adsorption mechanism and the position of amine derivative molecules towards the mild steel surface in an aggressive solution and to confirm the electrochemical results. The inhibition efficiency (IE) decreases with a decrease in concentration and the adsorption obeyed the Langmuir isotherm. The substitution of the OH group on the aromatic ring by Cl or CN increases IE to 90.23 and 92.56%, respectively. Molecular dynamics simulations attested that the four molecules were adsorbed on the Fe (110) surface in a flat position in the presence of water and HCl with high interaction between the different groups of the inhibitors and mild steel surface.

Discovery and Characterization of R/S-N-3-Cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)urea, a New Histone Deacetylase Class III Inhibitor Exerting Antiproliferative Activity against Cancer Cell Lines.

A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting sirtuins in glioma cells. On the basis of computational docking combined to in vitro sirtuin 1/2 inhibition assays, we selected compound 18 [R/S-N-3-cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)urea] which displays a potent antiproliferative activity on various glioma cell types, assessed by quantitative videomicroscopy, eventually triggering senescence. The impact on normal glial cells was lower with a selectivity index of >10. Furthermore, human U373 and Hs683 glioblastoma cell lines served to demonstrate the inhibitory activity of 18 against histone deacetylase (HDAC) class III sirtuins 1 and 2 (SIRT1/2) by quantifying acetylation levels of histone and non-histone proteins. The translational potential of 18 was validated by an NCI-60 cell line screen and validation of growth inhibition of drug resistant cancer cell models. Eventually, the anticancer potential of 18 was validated in 3D glioblastoma spheroids and in vivo by zebrafish xenografts. In summary, compound 18 is the first representative of a new class of SIRT inhibitors opening new perspectives in the medicinal chemistry of HDAC inhibitors.

Synthesis, characterization and biological evaluation of benzothiazoles and tetrahydrobenzothiazoles bearing urea or thiourea moieties as vasorelaxants and inhibitors of the insulin releasing process.

A series of 1,3-benzothiazoles (series I) and 4,5,6,7-tetrahydro-1,3-benzothiazoles (series II) bearing an urea or a thiourea moiety at the 2-position were synthesized and tested as myorelaxants and inhibitors of insulin secretion. Several compounds (i.e. 13u and 13v) from series I showed a marked myorelaxant activity. Benzothiazoles bearing a strong electron withdrawing group (NO2, CN) at the 6-position and an alkyl group linked to the urea or the thiourea function at the 2-position were found to be the most potent compounds. The weak vasorelaxant activity of series II compounds evidenced the necessity of the presence of a complete aromatic heterocyclic system. The myorelaxant activity of some active compounds was reduced when measured on aorta rings precontracted by 80 mM KCl or by 30 mM KCl in the presence of 10 µM glibenclamide, suggesting the involvement of KATP channels in the vasorelaxant effect. Some compounds of series I tested on rat pancreatic islets provoked a marked inhibition of insulin secretion, among which 13a exhibited a clear tissue selectivity for pancreatic ß-cells.

Design and synthesis of new potassium channel activators derived from the ring opening of diazoxide: study of their vasodilatory effect, stimulation of elastin synthesis and inhibitory effect on insulin release.

Benzenesulfonylureas and benzenesulfonylthioureas, as well as benzenecarbonylureas and benzenecarbonylthioureas, were prepared and evaluated as myorelaxants on 30mMKCl-precontracted rat aortic rings. The most active compounds were further examined as stimulators of elastin synthesis by vascular smooth muscle cells and as inhibitors of insulin release from pancreaticß-cells. The drugs were also characterized for their effects on glycaemia in rats. Benzenesulfonylureas and benzenesulfonylthioureas did not display any myorelaxant activity on precontracted rat aortic rings. Such an effect could be attributed to their ionization at physiological pH. By contrast, almost all benzenecarbonylureas and benzenecarbonylthioureas displayed a myorelaxant activity, in particular the benzenecarbonylureas with an oxybenzyl group linked to the ortho position of the phenyl ring. The vasodilatory activity of the most active compounds was reduced when measured in the presence of 80mMKCl or in the presence of 30mM KCl and 10µM glibenclamide. Such results suggested the involvement, at least in part, of KATP channels. Preservation of a vasodilatory activity in rat aortic rings without endothelium indicated that the site of action of such molecules was located on the vascular smooth muscle cells and not on the endothelial cells. Some of the most active compounds also stimulated elastin synthesis by vascular smooth muscle cells. Lastly, most of the active vasorelaxant drugs, except 15k and 15t at high concentrations, did not exhibit marked inhibitory effects on the insulin releasing process and on glycaemia, suggesting a relative tissue selectivity of some of these compounds for the vascular smooth muscle.