Mini Reviews in Medicinal Chemistry - Volume 7, Issue 7, 2007

Flavonoids are ubiquitously in plants which have been shown to possess a variety of biological activities at nontoxic concentrations in organisms. Compelling data indicate that flavonoids have important effects on cancer chemoprevention and chemotherapy, till now, much research has been done about their potential anticancer effect. In this review the discovery and development of flavonoids as potential anticancer agents in recent years have been summarized.

This article reviews synthesis and structures of carbaglycosylamines, a group of carbocyclic sugar analogues. Some unsaturated derivatives are known to be potent glycosidase inhibitors. Among them, N-octyl-4-epi-??-valienamine as a lysosomal ??-galactosidase inhibitor is currently undergoing a new molecular therapeutic trial (chemical chaperone therapy) for control of the human ??-galactosidase deficiency disorder, GM1-gangliosidosis.

The importance of the trace element selenium for human health is well established. Selenium plays a central role in the formation of selenocysteine, a modified amino acid located in the catalytic center of selenoenzymes. The crucial role of selenium in these enzymes revolves around the maintenance of many redox systems in cellular and extracellular compartments. In addition, selenium plays an important role in thyroid hormone metabolism. Several clinical trials of selenium supplementation in critically ill patients have been conducted to date, providing an interesting and provoking mix of findings. Despite some promising results, no definitive answers regarding the effects of selenium supplementation on critically ill patient mortality or morbidity exist. Further research in the setting of well-designed, prospective, randomized trials is necessary to better define the role of selenium supplementation in critically ill patients.

Aptamers have been introduced to analytical applications, target validation, and drug discovery processes and, recently, applied directly as therapeutic agents. Aptamers can be generated by a method called SELEX (Systematic Evolution of Ligands by Exponential Enrichment). This is quite remarkable for such a young technology, which is only created in the early 1990s. This paper reviews recent new applications of aptamers in stem cell research and tissue engineering.

HIV-1 integrase is one of the three enzymes, which are critical for viral replication. It catalyzes the integration of the HIV genome into the cellular chromosome. Since there is no known human homolog to integrase, its inhibition is one of the most promising novel drug targets for anti-retroviral therapy with potential advantage over existing therapies. To date, numerous compounds with diverse structural features have been reported as integrase inhibitors, among which the diketo-containing inhibitors of HIV-1 integrase represent a major lead for anti-HIV drug development. The discovery of diketo acids plays an important role in validating integrase as a legitimate target for treatment of AIDS. In this review, we summarize several drug candidates in clinical trials and new diketo-containing inhibitors of HIV-1 integrase discovered recently.

Base excision repair (BER) is the main pathway for repair of endogenous DNA damage. It was expected that different tumor types could derive from BER defects but to date this link is elusive. In vitro and molecular epidemiology studies may be used to unravel this issue.

Free heme contributes as a major threat to the oxidative tissue injuries because it catalyzes the formation of reactive oxygen species. When free heme concentration is increased, it results in the induction of heme oxygenase-1 (HO- 1), which then breaks free heme down. As such, HO-1 plays a pivotal role in the protection of tissues from oxidative injuries.

In the last decade novel therapeutic approaches for the treatment of cancer have been proposed: inhibitors of serine/threonine and tyrosine kinases, angiogenesis inhibitors, gene therapy approaches and others. In some cases the clinical trials have confirmed the efficacy of these approaches. Here, we will review the discovered molecular targets for the treatment of testicular germ cell tumors.

Diabetes is a widespread disease, and its development and toxic effects on various organs have been attributed to increased oxidative stress. Metallothionein (MT) is a group of intracellular metal-binding and cysteine-rich proteins, being highly inducible in many tissues. Although it mainly acts as a regulator of metal homeostasis such as zinc and copper in tissues, MT was found to be a potent antioxidant and adaptive (or stress) protein to protect cells and tissues from oxidative stress. Studies showed that zinc-induced or genetically enhanced MT synthesis in the pancreas prevented the development of spontaneous or chemically-induced diabetes. Genetically or pharmacologically enhanced MT expression in various organs including heart and kidney provided significant protection from diabetes-induced organ dysfunction such as cardiomyopathy and nephropathy. These studies suggest that MT as an adaptive protein can prevent both diabetes development and diabetic complications. This mini-review will thus briefly describe MT’s biochemical features and then summarize the data on the protective effect of MT against diabetes and diabetic complications. In addition, the coordinative role of MT with zinc in the prevention of diabetes and its complications will also be discussed.