Synthesis and biological evaluation of N-(4-hydroxy-3-mercaptonaphthalen-1-yl)amides as inhibitors of angiogenesis and tumor growth.

A series of N-(4-hydroxy-3-mercaptonaphthalen-1-yl)amides were synthesized and investigated for their in vitro antiangiogenic activity. Among these compounds, 6d, which possesses an ortho-nitro group at the benzene ring, exhibited potent inhibitory effect on the proliferation of HUVECs, A549, K562, PC-3, HCT116, MDA-MB-231 and MCF-7 cells (IC50 = 5.34, 40.53, 10.81, 52.52, 10.19, 21.37 and 2.81 µM, respectively). Meanwhile, compound 6d inhibited in vitro angiogenesis markedly in both HUVECs tube formation assay and the rat thoracic aorta rings test. Further kinase assay study showed that compound 6d had good VEGFR2, ALK, AKT1 and ABL inhibitory activities and moderate EGFR and PDGFR-ß inhibitory activities. The data supports the further investigation of this class of compounds as potential antiangiogenic and anticancer agents.

Design, synthesis and biological evaluation of novel L-isoserine tripeptide derivatives as aminopeptidase N inhibitors.

Aminopeptidase N (APN/CD13) is one of the essential proteins for tumour invasion, angiogenesis and metastasis as it is over-expressed on the surface of different tumour cells. Based on our previous work that L-isoserine dipeptide derivatives were potent APN inhibitors, we designed and synthesized L-isoserine tripeptide derivatives as APN inhibitors. Among these compounds, one compound 16l (IC50 = 2.51 ± 0.2 µM) showed similar inhibitory effect compared with control compound Bestatin (IC50 = 6.25 ± 0.4 µM) and it could be used as novel lead compound for the APN inhibitors development as anticancer agents in the future.

Synthesis of a novel series of L-isoserine derivatives as aminopeptidase N inhibitors.

A series of novel L-isoserine derivatives were synthesised and evaluated for their ability to inhibit aminopeptidase N (APN)/CD13. In our preliminary biological results, some of these compounds possessed a potent inhibitory activity against the APN. Within this series, compound 14b not only showed similar enzyme inhibition (IC50 of 12.2 µM) compared with the positive control bestatin (half maximal inhibitory concentration (IC50) of 7.3 µM), but also had a potent antiproliferative activity against human cancer cell lines cells.

Novel aminopeptidase N (APN/CD13) inhibitors derived from chloramphenicol amine.

Aminopeptidase N (APN) is involved in different physiological and pathological processes of tumor cells, including proliferation, invasion, apoptosis and metastasis. Herein one series of compounds derived from commercially available (1S,2S)-2-amino-1-(4-nitrophenyl) propane-1,3-diol have been designed and synthesized. Furthermore, preliminary activity evaluation showed that some compounds elicited moderate inhibitory activity against APN with compounds 10e (IC(50)=6.1±0.5 µM) possessing the best efficacy, which could be used as the lead compound in the future for anticancer agents research.

Design, synthesis and biological evaluation of novel L-lysine ureido derivatives as aminopeptidase N inhibitors.

As the exopeptidase over-expressed in the cell surface of endothelial cells, aminopeptidase N (APN/CD13) is an essential target for tumor angiogenesis and metastasis. Based on the previous work of L-lysine amide derivatives in our laboratory, we designed and synthesized two series of L-lysine ureido derivatives as APN inhibitors. Within these compounds, one compound, 5d (IC50 = 4.51 µM), showed similar inhibitory effect compared with Bestatin (IC50 = 5.87 µM).

The effect of different species aminopeptidase N structure on the activity screening of aminopeptidase N inhibitor.

Aminopeptidase N (APN) is a transmembrane metallopeptidase, which participates in the tumor progress such as proliferation, attachment, angiogenesis and tumor invasion. All of this makes APN as a good chemical therapeutic anti-tumor target. In the present study, we got a novel compound 16l which markedly inhibited the enzyme activity of porcine APN, and the inhibition constant, K(i), of 16l are similar to the positive medicine Bestatin determined using porcine APN. However, when tested using human tumor cells, 16l couldn't effectively inhibit the enzyme activity, cell viability, cell migration and invasion. Computer aided drug design verified that because of the difference in structure, the binding pattern of 16l in the active site of homo sapien and porcine APN was different. The compound 16l could effectively inhibit the enzyme activity of porcine APN, but not homo sapien APN located on the surface of tumor cells. Therefore, the activity screening of APN inhibitor using aminopeptidase N from porcine should be only preliminary determination. The real activity screening should be determined using homo sapien aminopeptidase N.

An overview of highly optically pure chloramphenicol bases: applications and modifications.

Chloramphenicol (CAP) is a widely used broad-spectrum antibiotic. As the precursor of CAP, chloramphenicol bases are stereochemically pure agents and could be used as resolution agents, chiral catalysts and so on. This review summarizes these applications and discusses the structural modifications of chloramphenicol bases.

Potential targets and their relevant inhibitors in anti-influenza fields.

Influenza is a disease for deeply affecting millions of people every year. Recently, there has been considerable concern regarding the highly pathogenic H5N1 avian influenza virus, and its human pandemic potential. With developments in viral biology, there are more novel antiviral strategies targeting these viruses. In this review, we will discuss several proven and potential anti-influenza targets, including viral factors (such as hemagglutinin (HA), M2 ion channel protein, RNA-dependent RNA polymerase (RdRp), nucleoprotein (NP), non-structural protein (NS) and neuraminidase (NA)) and host factors (such as v-ATPase, protease, inosine monophosphate dehydrogenase (IMPDH) and intracellular signalling cascades), and their relevant inhibitors.

Design and synthesis of novel chloramphenicol amine derivatives as potent aminopeptidase N (APN/CD13) inhibitors.

Herein we report a series of novel chloramphenicol amine derivatives as aminopeptidase N (APN)/CD13 inhibitors. All compounds were synthesized starting from commercially available (1S,2S)-2-amino-1-(4-nitrophenyl) propane-1,3-diol. The preliminary biological screening showed that some compounds exhibited potent inhibitory activity against APN. It should be noted that one compound, 13b (IC(50)=7.1 microM), possess similar APN inhibitory activity compared with Bestatin (IC(50)=3.0 microM).

(S)-2-[(2R,3S)-2-Ammonio-3-hydr-oxy-3-(4-nitro-phen-yl)propanamido]-4-methyl-penta-noate monohydrate.

The structure of the title compound, C(15)H(21)N(3)O(6)·H(2)O, is of inter-est with respect to assumed anti-cancer activity. The title mol-ecules are linked through inter-molecular O-H⋯O hydrogen-bonded chains along the a axis. These chains are connected by inter-molecular N-H⋯O hydrogen bonds through the crystallographic screw axis along [010], forming layers, which are stabilized by other N-H⋯O bonds with water O atoms as acceptors and O-H⋯O bonds with water H atoms as donors. The H atoms of the protonated amino cation are also involved in inter-molecular N-H⋯O bonding inter-actions.

Recent advances in the research of P-glycoprotein inhibitors.

The ability of cancer cells to experience intrinsic or acquired resistance to a broad spectrum of structurally and functionally unrelated chemotherapeutic agents, termed multidrug resistance (MDR), is the most common cause of chemotherapy failure. Research has firmly established that most tumors developing MDR are often associated with the over-expression of permeability-glycoprotein (P-gp), the most extensively characterized of the drug efflux pumps. The development of P-gp inhibitors is acknowledged as a viable means of reversing this MDR phenotype and has received considerable attention throughout the past two decades. However, most P-gp inhibitors identified to date have demonstrated limited clinical success due to limitations in potency and specificity. This paper reviews the most recent discoveries relating to the medicinal chemistry of P-gp inhibitors that are presently in development. In light of this information, this paper seeks to suggest new treatment options for the MDR phenotype.