Synthesis and 4D-QSAR Studies of Alanine Hydroxamic Acid Derivatives as Aminopeptidase N Inhibitors.

Background: As a target for anticancer treatment, aminopeptidase N (APN) shows its overexpression on diverse malignant tumor cells and associates with cancer invasion, angiogenesis and metastasis.

Objective: The objective of the study was the design, synthesis and biological activity evaluation of alanine hydroxamic acid derivatives as APN inhibitors, and investigation of the binding mode of inhibitors in the APN active site.

Methods: Alanine hydroxamic acid derivatives were synthesized and evaluated for their in vitro anti-cancer activity using CCK-8 assay.

Synthesis and molecular simulation study of furoic peptidomimetic derivatives as potent aminopeptodase N inhibitors.

The aminopeptidase N (APN) plays a critical role in angiogenesis and is over-expressed in tumor cells. In this paper, we report the synthesis and enzyme inhibition assay of furoic peptidomimetic compounds. These new compounds exhibit potent inhibitory ability toward APN with IC50 values lying in the micromolar level.

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.

(2R,3R)-N-(4-Chloro-phen-yl)-2,3-dihydr-oxy-N'-(5-phenyl-1,3,4-thia-diazol-2-yl)succinamide.

In the structure of the title compound, C(18)H(15)ClN(4)O(4)S, the dihedral angle between the two benzene rings is 1.4 (3)°. The angle between the phenyl ring and thia-diazole ring is 5.

4-Chloro-N-[3-methyl-1-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)but-yl]benzamide.

In the title compound, C(14)H(16)ClN(3)O(2)S, the dihedral angle between the 4-chloro-phenyl and 1,3,4-oxadiazole rings is 67.1 (1)° and the orientation of the amide N-H and C=O bonds is anti. In the crystal, mol-ecules are linked by N-H⋯O and N-H⋯S hydrogen bonds.

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.

2-Benzoyl-amino-N-[5-(4-bromo-phen-yl)-1,3,4-thia-diazol-2-yl]ethanamide.

In the structure of the title compound, C(17)H(13)BrN(4)O(2)S, the dihedral angle between the two benzene rings is 38.5 (1)°; the angle between the 4-bromo-benzene and thia-diazole rings is 1.3 (1)°.

1-(3-Chloro-benz-yloxy)urea.

The asymmetric unit of the crystal structure of the title compound, C(8)H(9)ClN(2)O(2), contains four independent mol-ecules. The dihedral angles between the urea N-(C=O)-N planes and the benzene rings are 83.3 (3), 87.

The synthesis and preliminary activity assay in vitro of peptide-like derivatives as APN inhibitors.

Both the aminopeptidase N (APN) and matrix metalloproteinase (MMP) are essential metallopeptidases in the development of tumor invasion and angiogenesis. A series of novel peptide-like derivatives were designed and synthesized as antitumor agents. Their structures were confirmed by IR, MS, and (1)H-NMR.

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.

Progress in the development of matrix metalloproteinase inhibitors.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the degradation and remodeling of extracellular matrix proteins that are associated with the tumorigenic process. MMPs promote tumor invasion and metastasis, regulating host defense mechanisms and normal cell function.Thus, MMP inhibitors (MMPIs) are expected to be useful for the treatment of diseases such as cancer, osteoarthritis, and rheumatoid arthritis.

(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)°.

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

The asymmetric unit of the title compound, C(21)H(20)N(4)O(3)S, contains two independent mol-ecules. The dihedral angles between the two benzene rings are 47.6 (1) and 30.