Current Medicinal Chemistry - Volume 16, Issue 3, 2009

High-throughput screening campaigns are fuelled not only by corporate or “maximally diverse” compound collections, but increasingly accompanied by target- or bioactivity-focused selections of screening compounds. Computerassisted library design methods aid in the compilation of focused molecule libraries. A prerequisite for application of any such computational approach is the definition of a reference set and Read More

The Human Immunodeficiency Virus (HIV) genome encodes three major structural proteins common to all retroviruses (Gag, Pol and Env), two regulatory proteins (Tat and Rev) that are essential for viral replication, and four accessory proteins (Nef, Vif, Vpu, Vpr). While accessory proteins were initially reported to be unnecessary for viral growth, their importance as virulence factors is now being more and more appreciate Read More

Anticancer drug-induced tumor suppression may involve mechanisms of protection against neoplastic transformation that are normally latent in mammalian cells and consist in a genetic program implemented during anti-tumoral defense. This defense program results in the self elimination of cells harboring potentially dangerous mutations by triggering cell death through apoptosis and/or autophagy or in the execution of a Read More

Chemoresistance is a general health problem concerning infectious diseases and cancer treatments. In this context, the worldwide dissemination of ≪ pandrug ≫ and ≪ multidrug≫ resistant pathogens has severely compromised the efficacy of our antimicrobial weapons and dramatically increased the occurence of therapeutic failure. To efficiently combat multi-resistant pathogens, it is necessary to clearly define the mole Read More

Fourier-transform infrared (FT-IR) based mapping and imaging is a fast emerging technology which is being increasingly applied to investigate tissues in the high-throughput mode. The high resolution close to the cellular level, the possibility to determine the bio-distribution of molecules of interest (proteins, peptides, lipids, carbohydrates) without any pre-treatment and the offer to yield molecular structure information have Read More

Podophyllotoxin is an important and much sought after antimitotic natural lead compound, since it paved the way for three hemisynthetic derivatives of podophyllotoxin, e.g., etoposide, teniposide and etopophos, which are widely used as anticancer drugs and show good clinical effects against several types of neoplasms. Although the publication of the recent reviews by Gordaliza in 2004 and You in 2005, which covered Read More

Long term caloric restriction is known to counteract aging and extend lifespan in several organisms from yeasts to mammals. Recent research has provided solid ground to the concept that limiting calorie intake slows down brain aging and protects from age-related neurodegenerative diseases. The present review summarizes the most relevant among these data and highlights some genetic and molecular mechanisms responsib Read More

Proteins almost never act in an isolated manner; they interact with other proteins in order to perform essential roles in many important cellular processes. Apart from their ability to form stable multiprotein complexes, proteins associate transiently with their targets to modify, regulate by steric effects, or translocate them to different cellular compartments. Therefore, the identification of molecules able to modulate such p Read More

Prion diseases are zoonotic infectious diseases caused by infectious particles, termed prions. Main component of prions is presumably a misfolded, partially protease-resistant conformer (PrPSc) of a normal cell surface protein, the cellular prion protein (PrPC), whose anti-oxidative role is presumed by studies using prion protein (PrP)-knockout mice and cell lines. Major common features of prion diseases are PrPSc depositi Read More

Ensuring the availability of new antibiotics to eradicate resistant pathogens is a critical issue, but very few new antibacterials have been recently commercialized. In an effort to rationalize their discovery process, the industry has utilized chemical library and high-throughput approaches already applied in other therapeutical areas to generate new antibiotics. This strategy has turned out to be poorly adapted to the reality Read More