Design, synthesis of novel Triazolones and bis-Triazolones derivatives under ultrasound irradiation and evaluation as potent angiotensin converting enzyme (ACE) inhibitors.

The condensation of several primary amines and diamines with various N1-ethoxycarbonyles N1-tosylhydrazonates (1a-b), triazolones (2) and bis-triazolone (3) resulted in ethanol under ultrasound irradiation. Compared with the conventional methods, the main advantages of the present procedure are milder conditions, shorter reaction time and higher yields. The newly synthesized compounds were evaluated for angiotensin I-converting enzyme (ACE) inhibition. The results were compared to Captopril as a reference drug. Compounds 3b, 2h, 3a, 2d, and 2f showed not only inhibition activity with IC50 values of 0.162, 0.253, 0.253, 0.281 and 0.382 µM, respectively, but also minimal toxicity. The docking of chemical compounds in the ACE active site showed possible inhibitory effect of all compounds on the catalytic activity of the enzyme, which would satisfactorily explain the anti-hypertensive effect of these compounds.

Synthesis and evaluation of new bis-1,3,4,2-triazaphospholinoalkane derivatives as in vitro α-amylase and lipase inhibitors.

A series of new 1,ω-bis-(5-alkyl-2-oxide-3-tosyl-1,3,4,2-triazaphospholino)alkanes 2 and 3 were prepared in good yields by the treatment of 1,ω-bis-(1-tosylamidrazone)alkanes 1 with two molar equivalents of phosphoryl trichloride and phenylphosphonic dichloride, respectively. All the newly synthesized compounds were characterized by IR, (1) H NMR, (13) C NMR, (31) P NMR, and elemental analysis. All the new compounds were screened for their inhibitory effect on the key enzymes related to diabetes and obesity, as α-amylase and lipase. The in vitro study revealed that these alkane derivatives exert an inhibitory action against these key enzymes, especially 2b with an IC50 of 16 µg/mL against α-amylase and lipase. Overall, the findings of the current study indicate that 2d exhibits attractive properties and can therefore be considered for future application in the development of antidiabetic and hypolipidemic drugs.