Mini Reviews in Medicinal Chemistry - Volume 9, Issue 10, 2009

This article reviews the characteristics of the main fluoroquinolones used in dentistry (ciprofloxacin, levofloxacin and moxifloxacin), including pharmacokinetic/ pharmacodynamic parameters, susceptibility profiles of oral bacteria and clinical trials on their efficacy in dental practice. It seems that some of these antibiotics might represent a safe alternative in patients with allergy, intolerance, or lack of response to beta-lactams.

Antimicrobial peptides (AMPs) are one of the components of the non-specific immune system that operate first lines of protection in many animal species including fish. They exert broad-spectrum antimicrobial activity, apart from many other potential roles in innate immunity, and represent a promising class of antiviral agents. Recent advances in understanding the mechanisms of their antiviral action(s) indicate that they have a dual role in antiviral defence, acting not only directly on the virion but also on the host cell. Despite the acute problems of viral diseases and restrictions in using chemicals in aquaculture, few but successful attempts to assess the antiviral activities of fish AMPs have been reported. This review focuses on the antiviral activities and mechanisms of action of some AMPs, and their potential relevance in the aquaculture industry, one of the most important sources of fishery products in the near future. It is a matter of notable concern to understand whether the AMPs can be used as model molecules for designing antiviral drugs that might help to solve the problems with viruses in the fish farming industry worldwide. In addition, because fish rely more heavily on their innate immune defences than mammals, they might constitute a potential rich source of antiviral compounds for fighting against mammalian viral infections.

Thrombin-activatable fibrinolysis inhibitor (TAFI) provides an important molecular link between the coagulation and fibrinolytic systems. In this review, recent major advances in TAFI research, including the elucidation of crystal structures, the development of small inhibitors and the role of TAFI in systems other than hemostasis, are described and discussed.

Microtubules are cytoskeletal components that play important roles in a number of cellular processes. Colchicine binding site inhibitors (CSIs) is one major class of tubulin polymerization inhibitors, inhibiting microtubule polymerization and blocking cell proliferation at metaphase during mitosis. Many CSIs were discovered or designed and synthesized as anticancer agents in the past several years and great progress had been made. Here, we discuss the insights gained so far relevant to the mechanism of CSIs and their common pharmacophore. The recent development of CSIs with their biological activity and structure-activity relationship (SAR) are also reviewed.

Estrogen has important physiological effects on the growth and function of hormone-dependent tissues, and the link between estrogen and breast cancer has been deciphered at the end of the 20th century. Tamoxifen, one of the first generation selective estrogen receptor modulators (SERMs), has been the gold standard of first-line therapeutic drugs for all stages of estrogen-dependent breast cancer and has been found to reduce the incidence of breast cancer in high-risk pre- and postmenopausal women. Raloxifene, a second-generation SERM, was recently approved by FDA to decrease the risk of invasive breast cancer in postmenopausal women. During these years, many other novel types of SERAMs are being studied. This review highlights their recent advances. The discovery of selective estrogen receptor alpha modulators (SERAMs) and the latest information about their clinical and preclinical trials will be introduced intensively.

An all out war is continuously occurring between oxidants and antioxidants inside the cells. This mini-review will provide an updated revision of the function of some natural compounds having main roles in antioxidant function. We will point on some phytochemicals working at two outstanding targets, tumour cells and neurons.

The chemokine CX3C-L/FKN is expressed in both soluble and transmembrane/mucin hybrid forms, thus combining chemoattractant functions together with receptor/adhesion molecule properties. In contrast to other chemokine receptors, CX3C-R is expressed not only on lymphoid cell populations, but also on several intrinsic cells including tubular epithelial cells and renal fibroblasts where it regulates various aspects of cell viability, matrix synthesis and degradation, migration, inflammation as well as oxidative stress. In the kidney, the chemokines/receptor pair has been shown to play a role in nephrogenesis as well as in the pathogenesis primary and secondary nephropathies. In several animal models and human specimens with acute and chronic renal failure including allograft nephropathy, CX3C-L/CX3C-R has been shown to exert immune and non-immune mediated renal damages. A blockade of this chemokine system ameliorated acute and chronic renal damages, though the latter to a more robust extent. There seems to a role of the CX3C-L/CX3C-R pair in mediating acute renal inflammation as well as in progressive chronic renal failure. However, functional studies are lacking for many aspects and further studies are necessary to better define the functional properties of CX3C-L/FKN and its receptor.

The identification of peripheral biomarkers for neurodegenerative diseases is required to improve the accuracy of clinical diagnosis and monitor both disease progression and response to treatments. The data reviewed in this paper suggest that, in neurodegenerative disease, cytokines are links between peripheral immune system and nervous system dysfunction.

The design and synthesis of safe efficient non-viral vectors for gene delivery has attracted significant attention in recent years due primarily to the severe side-effect profile reported with the use of their viral counterparts. Previous experiments have revealed that the strong interaction between the carriers and nucleic acid may well hinder the release of the gene from the complex in the cytosol adversely affecting transfection efficiency. However, incorporating reducible disulfide bonds within the delivery systems themselves which are then cleaved in the glutathione-rich intracellular environment may help in solving this puzzle. This review focuses on recent development of these reducible carriers. The biological rationale and approaches to the synthesis of reducible vectors are discussed in detail. The in vitro and in vivo evaluations of reducible carriers are also summarized and it is evident that they offer a promising approach in non-viral gene delivery system design.