L-iso-glutamine derivatives as an APNIs was prepared by the condensation reaction of N-(3,4,5-trimethoxybenzoyl)-glutamic acid anhydride with L-amino acid methyl ester hydrochloride. The structure was confirmed by the methods of IR, 1H NMR, MS, elemental analysis, HMBC Spectrum and X-ray single crystal diffraction.

A series of novel 2-acyloxymethyl-3,5,6-trimethylpyrazine derivatives was designed and synthesized. Most compounds were found to be 1.5-4.5-fold higher potency than tetramethylpyrazine (TMP) in stimulating the proliferation of normal vascular endothelial cells and in protecting against hyperoxic acute injury. The most active one is the 2-nicotinoyl ester 5a exhibiting the maximum proliferation rate (Pmax) of 88.57% at the concentration of 0.1 mmol L1. Structure-activity relationships of these compounds were discussed.

The synthesis and biological evaluation of caffonyl pyrrolidine derivatives as MMPs inhibitors are reported in this paper. Inhibiting activities of synthesized compounds on gelatinase (MMP-2 and -9) were tested by using succinylated gelatin as substrate. Structure－activity relationship results from these tested compounds demonstrated that longer and more flexible side chain linked to the pyrrolidine ring at C4 produced higher activity at gelatinase. Furthermore, aromatic heterocycle and sulfamide in the same position could enhance the activities. Compounds with free phenol hydroxyl group showed higher activity compared to methylated derivatives (or counterparts), which confirms the importance of phenol hydroxyl functionality in the interaction with gelatinase. The anti-metastasis model of mice bearing H22 tumor cell was used to evaluate their in vivo inhibiting activities. All tested compounds were orally administered at a dose of 50 or 100mg/kg, 6days/week for two weeks. The test results demonstrated that most of these inhibitors showed significant anti-cancer activities (inhibitory rate > 35%) and were devoid of toxic effects. Compound 29 showed the highest inhibitory rate at 69.25%, indicating that it might be a promising lead compound.

The aim of this study was to design and characterize lectin-modified liposomes containing insulin and to evaluate the potential of these modified colloidal carriers for oral administration of peptide and protein drugs. Wheat germ agglutinin (WGA), tomato lectin (TL), or Ulex europaeus agglutinin 1 (UEA1) were conjugated by coupling their amino groups to carbodiimide-activated carboxylic groups of N-glutaryl-phosphatidylethanolamine (N-glut-PE). Insulin dispersions were prepared by the reverse-phase evaporation technique and modified with the lectin-N-glut-PE conjugates. Lectin-modified liposomes were characterized according to particles size, zeta potential and entrapment efficiency. The hypoglycemic effect of the lectin-modified pharmacological bioavailability of insulin liposomes modified with WGA, TL and UEA1 were 21.40, 16.71 and 8.38% in diabetic mice as comparison with abdominal cavity injection of insulin, respectively. After oral administration of the insulin liposomes modified with WGA, TL and UEA1 to rats, the relative pharmacological bioavailabilities were 8.47, 7.29 and 4.85%, the relative bioavailability were 9.12, 7.89 and 5.37% in comparison with subcutaneous injection of insulin, respectively. In the two cases, no remarkable hypoglycemic effects were observed with the conventional insulin liposomes. These results confirmed that lectin-modified liposomes promote the oral absorption of insulin due to the specific-site combination on GI cell membrane.

Aminopeptidase N (APN; CD13) is a member of zinc-containing ectoenzymes family involved in the degradation of neutral or basic amino acids (Ala>Phe>Leu>Gly) from N-terminal of bioactive peptides and amide or arylamide derivatives of amino acids. The expression of APN being up regulated has been implicated in the pathogenesi of a variety of diseases such as cancer, leukemia, diabetic nephropathy, and rheumatoid arthritis. Thus, APN inhibitors (APNIs) are expected to be useful for the treatment of these disorders. This article reviews briefly the structure characteristic and possible function of APN. The proposed biomolecular structures and mechanism of action used in the design of APNIs are thoroughly covered. Major emphasis is on recently published potent, small molecular weight APNIs and their essential structure activity relationship (SAR). Finally, available clinical results of compounds in development are summarized in this review.