Mini Reviews in Medicinal Chemistry - Volume 6, Issue 10, 2006

The field of naturally occurring antimicrobial peptides is a research area rapidly expanding due to the high potential of such molecules as new antimicrobial drugs. In this regard, the human beta-defensin-3 is particularly attractive because of its strong antibacterial activity, relative salt-insensitiveness and low toxicity for host cells.

Amyloid &bgr:-protein (Aβ) plays a pivotal role in Alzheimer's disease (AD). Therapeutic strategies inhibiting Aβ aggregation and promoting extracellular Aβ removal are currently advocated. Here, we review recent literature on intracellular Aβ, especially intranuclear Aβ, and its associated molecules. We also discuss alternative therapeutic strategies to inhibit intracellular A β-related pathogenesis.

Solid organ transplantation was one of the greatest medical advances of the 20th century. Current preservation technology falls short of maintaining organs ex vivo in perpetuity. This review examines the biochemical basis of organ degradation in response to ischaemia, preservation solution composition and potential future organ preservation technology.

Medical sensing systems using isolated or intact glutamate receptor (GluR) ion channels and glutamate oxidase (GluOx) are discussed for L-glutamate, one of the principal neurotransmitter in the central nervous systems of mammalian brain, and related agonists. The GluR-based sensing system used for the evaluation of signal transduction ability of GluR channels demonstrate that the agonist selectivity based on the sign Read More

Small molecule protein kinase inhibitors show great promise as anti-cancer agents, however, de novo and acquired resistance present problems. These are reviewed and illustrated using the receptor tyrosine kinase, KIT, as an example. Emerging solutions are presented, such as targeting active kinase conformations.

Recombinant factor VIIa (rFVIIa) is a synthetic coagulation protease that is structurally similar to humanderived plasma FVIIa. Pharmacologic doses of rFVIIa have been shown to enhance thrombin generation and assist in forming stable fibrin plugs at the site of injury. Recombinant factor VIIa appears to emerge as a valuable treatment alternative for the treatment of bleeding episodes and for achieving hemostasis post surger Read More

The study of the Urocortin family of peptides is becoming increasingly important clinically, as new discoveries have revealed that their roles in the body are extremely diverse. They range from being involved in the aetiology of affective disorders, boosting the immune system, to cardioprotection during ischaemia and reperfusion injury. Therefore, it is important to understand how these peptides become activated Read More

Phosphatidylinositol 3-kinase (PI3K) and serine/threonine protein kinase B (PKB or Akt) pathways regulate important cellular processes and are related to a number of human pathologies, such as cancer. The development of kinase inhibitors, with particular attention to small molecule analogues of natural phosphoinositides for pathway interruption and therapeutic applications will be reviewed.

Hsp90 is a chaperone with over 100 identified client proteins. What makes Hsp90 especially promising as a target for anti-cancer drugs is that many of its client proteins are in signaling and chromatin-remodeling pathways, and these pathways are often disrupted in many types of cancers. Recently, it was determined that Hsp90 bound to a client protein in a co-chaperone complex has a higher ATPase activity and binds to th Read More

Bisindole Vinca alkaloids target microtubule system causing anti-mitotic activity. The problem of their clinical application is the lack of selectivity resulting in toxic side effects. In this paper we review the late history of new bisindole derivatives focusing on KARs recognized as potent anti-cancer drugs with low side effect. KARs, just as other bisindoles, impede microtubule assembly of mitotic spindle, however, they display Read More

The cost of pharmaceutical development has increased dramatically in recent years, and many assorted approaches have been developed to decrease both the time and costs associated with bringing a drug to the market. Among these methods is the use of in silico screening of compound databases for potential new lead compounds, commonly referred to as virtual screening (VS). Virtual screening has become Read More

The application of organosilicon chemistry is a strategy to develop best in class drugs applied to targets that have been validated as tractable and drug-able. Silicon switches of known drugs have been synthesised and evaluated in biological assay systems then compared to their marketed all-carbon counterparts. Recent examples include the silicon switches of drugs haloperidol, fexofenadine, bexarotene and venlafaxine.