Exploring ligand dissociation pathways from aminopeptidase N using random acceleration molecular dynamics simulation.

Aminopeptidase N (APN) is a zinc-dependent ectopeptidase involved in cell proliferation, secretion, invasion, and angiogenesis, and is widely recognized as an important cancer target. However, the mechanisms whereby ligands leave the active site of APN remain unknown. Investigating ligand dissociation processes is quite difficult, both in classical simulation methods and in experimental approaches.

3D-QSAR studies on flavone-8-acetic acid derivatives of aminopeptidase N inhibitors.

The 3D-QSARs models of 29 flavone-8-acetic acid derivatives of aminopeptidase N inhibitors were generated by applying the molecular interaction fields at various 3D grid spacing. The cross-validated correlation coefficient q(2)LMO (0.6019) and conventional correlation coefficient r(2) (0.

Synthesis and antiproliferative assay of norcantharidin derivatives in cancer cells.

Diels-Alder reaction between furan and maleic anhydride resulted in 5,6-dehydro norcantharidin, then norcantharidin was obtained by reduction. The substituted-carboxylic acid was condensed with N-aminothiourea in presence of phosphorus oxychloride, yielding 2-amino-1,3,4-thiadiazole derivatives. Novel norcantharidin derivatives were synthesized with acylation, then intramolecular condensation using norcantharidin (or 5,6-dehydro norcantharidin) and 2-amino- 1,3,4-thiadiazole derivatives.

Design, synthesis and biological evaluation of CB1 cannabinoid receptor ligands derived from the 1,5-diarylpyrazole scaffold.

The CB1 receptor belongs to the G-protein-coupled receptor superfamily. CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. In this study, we report the synthesis and in vitro binding affinity assay of some 1,5-diarylpyrazole scaffold compounds.

Synthesis of 1,3,4-thiadiazole derivatives as aminopeptidase N inhibitors.

Aminopeptidase N (APN) is a zinc-dependent ectopeptidase which plays an important role in the invasion of metastatic tumors. In this study, we report the synthesis and in vitro enzyme inhibition assay of 1,3,4-thiadiazole scaffold compounds. These new compounds have potent inhibitory activities toward APN with IC50 values in the micromolar range.

Novel aminopeptidase N inhibitors derived from 1,3,4-thiadiazole scaffold.

The aminopeptidase N (APN/CD13), overexpressed in tumor cells, plays a critical role in angiogenesis. In this study, we report the synthesis and in vitro enzyme inhibition assay of 1,3,4-thiadiazole scaffold compounds. These new compounds have potent inhibitory activities toward APN with IC(50) values in the micromol rang.

(2R)-N-[5-(4-Chloro-phen-yl)-1,3,4-thia-diazol-2-yl]-2-(cinnamoylamino)propanamide.

In the title compound, C(20)H(17)ClN(4)O(2)S, the dihedral angle between the two benzene rings is 65.9 (1)°; the corresponding angle between the 4-chloro-phenyl and thia-diazole rings is 3.4 (8)°.