Mini Reviews in Medicinal Chemistry - Volume 10, Issue 3, 2010

The InhA-related enoyl-ACP reductase, an enzyme involved in fatty acid synthesis, is one of the best validated targets for the development of anti-tubercular agents. However, the majority of isoniazid (INH)-resistant clinical strains are observed mainly due to the emergence of KatG mutants that do not form an INH-NAD adduct. Thus compounds that directly inhibit InhA avoiding activation by KatG would be promising candidates for combating MDR-TB. Herein, some predominant examples of InhA direct inhibitors recently developed are reviewed and special attention is paid to 3Dstructures of InhA in drug design process.

Magnetic iron oxide nanoparticles have attracted extensive interest as novel contrast agents for biomedical imaging owing to their capability of deep-tissue imaging, non-invasiveness and low toxicity. This mini-review will provide an overview on the recent synthesis methods, influencing factors and potential applications of magentic nanoparticles for cell labeling and imaging.

Niacin has broad spectrum lipid modifying and anti-atherosclerotic properties. It is the most effective medication available for raising raise high density lipoprotein (HDL) levels. Despite statin therapy there remains a considerable residual cardiovascular risk attributed to low HDL levels. Currently, statins decrease cardiovascular events and death by about 25-40%. Trials with surrogate endpoints have shown a decrease in endpoints by 60-90% when a combination of statin and niacin has been used. There is a growing interest in niacin in combination therapy to fill the treatment gap by modifying lipid parameters other than low density lipoprotein cholesterol. This review addresses the role of niacin in comprehensive lipid management with an emphasis on its mechanism of action, formulations, side effects, evidence from clinical trials and also focuses on practical issues related to niacin therapy.

The present review focused on the strategies aimed to possibly solve toxicity problems of distamycins. Distamycins are compounds characterized by an oligopeptidic pyrrolocarbamoyl frame ending with an amidino moiety. This class of compounds displays antiviral and antibiotic activity and shows interesting antiprotozoal activity related to the ability to reversibly bind to the minor groove of DNA with a high selectivity for TA-rich sequences. In consideration of their potential therapeutic properties, the synthesis of new distamycin derivatives and especially the development of controlled delivery strategies, could lead to important advantages in the clinical use of these molecules, possibly overcoming or mitigating the low solubility, specificity and toxicity problems associated with their use. To these aims an ensemble of the main synthetic distamycin derived compounds and of the potential drug delivery systems for distamycins described in literature is reviewed.

Elevated lipid level is supposed to be one of the main risk factors of atherosclerosis and related cardiovascular diseases and stroke (and is connected to mortality and morbidity). Therefore, lipid lowering is one of the major approaches in prevention of coronary heart diseases and stroke. Though drugs of various categories acting through different mechanisms are available in the antihyperlipidemic therapy, there are still a few problems associated with the currently available lipid lowering drugs. Therefore, medicinal chemists worldwide are designing, synthesizing and evaluating a variety of new molecules for antihyperlipidemic activity to address these problems. One of the important approaches to this is identifying new drug targets for antihyperlipidemic activity. This review summarizes nineteen recently identified and currently being exploited targets for the ongoing research by researchers world over to discover novel leads as potential drugs for antihyperlipidemic therapy.

The first generation of in vitro models providing successful isolation of viable brain endothelial cells from different species, which could be maintained in cell culture, have emerged around thirty years ago. However, the time consuming and the difficulty of working with primary culture cells led to the development of simpler models employing cell lines with blood-brain barrier properties. The creation, in late nineties, of a transgenic mouse harboring the temperature sensitive simian virus 40 large T-antigen as a source of conditionally immortalized brain endothelial cell lines circumvented the problems of in vitro transfection of tumour inducing gene in primary cells. These different ways to obtain cultures of brain endothelial cells have profited from the discovery of different cellular factors that allow the growth of differentiated cells on plastic filters. Although cell preparations and culture conditions of brain endothelial cells are based on the same principle, there are two main models for studying the blood-brain barrier: the static and the more recently described dynamic model. Dynamic models were created in order to replicate the physiological in vivo environment of the blood-brain barrier. The large pool of in vitro models is being enlarged since each laboratory improves its model adding small differences adapted to the research interests. The great impact of blood-brain barrier studies in the development of therapies related to the central nervous system supports the interests of this review about in vitro models.