Pseudo-allergic reactions may result from the activation of inflammatory or anaphylactic mechanisms independent of antigen-specific immune responses. Recent statistics show that pseudo-allergic reactions may represent as high as two thirds of all immediate hypersensitivity reactions, implying a great amount of morbidity and numerous health care costs. In this review, we concentrate on agents mediating pseudo-allergic reactions and evaluate accurately the available information on their modes of action. The agents discussed here are divided into three types: (i) Direct mast cell activators, which may activate mast cells in an IgE-independent manner, such as opioid drugs, basic secretagogues and calcium ionophore A23187; (ii) Complement activators, including liposomes, radiocontrast media and Cremophor EL, which may activate the complement system by different pathways: the classical pathway, the mannose-binding lectin pathway or the alternative pathway; (iii) Nonsteroidal anti-inflammatory drugs, which may inhibit the function of cyclooxygenase-1, resulting in the occurrence of adverse reactions. In addition, nonclinical detection methods of pseudoallergic reactions are also reviewed in order to supply valuable information for clinical diagnosis.
Invasion and metastasis, the hallmark of malignant tumor, is the main reason for the clinical death of most cancer patients. Tumor invasion and metastasis are complex, multi-step biochemical processes, which involve cell detachment, invasion, migration, intravasation and circulation, implantation, angiogenesis and proliferation. Therefore, how to prevent tumor metastasis has been the biggest challenge in cancer chemotherapy. In recent years, many natural products have been found to have anti-invasive and anti-metastatic activities. In this paper, these natural compounds are classified as polyphenols, terpenoids, alkaloids, steroids and saponins, saccharides, macrolides, amides and others, their anti-invasive and anti-metastatic activities as well as their biological targets are reviewed.
HIV protease plays a crucial role in the viral life cycle by processing the viral Gag and Gag-Pol polyproteins into structural and functional proteins essential for viral maturation. Inhibition of HIV-1 protease leads to the production of noninfectious virus particles and hence is an important therapeutic target for antiviral therapy in AIDS patients. Among many strategies to combat this disease, highly active antiretroviral therapy (HAART) with HIV protease inhibitors (PIs) in combination with reverse transcriptase inhibitors and fusion inhibitor continues to be the first line treatment for control of HIV infection. However, the rapid emergence of drug-resistant HIV-1 strains and the appearance of cross-resistance are severely limiting the long-term treatment options. Thus, numerous efforts have been made in the design and synthesis of novel protease inhibitors with broad-spectrum activity against multidrug-resistant HIV-1 variants by medicinal chemists. This review will focus on the substrate-based drug design of novel peptidomimetic PIs in recent years since 2006.
Guanine-rich DNA sequences can form planar four-stranded structures via Hoogsteen hydrogen bonds. These sequences in telomeric DNA and some oncogenes have been identified as targets for novel anticancer drugs. Consequently, there is great current interest in developing small molecules that can facilitate the formation of, and stabilize G-quadruplexes as potent antitumor chemotherapeutic agents. Metal complexes with planar geometries and phi-delocalised ligands are emerging as a new class of quadruplex DNA ligand with unique features for optimal binding. This review will summarize the different types of metal-based compounds that target G-quadruplexes and provide useful information on the design of small ligands.
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