Current Medicinal Chemistry - Volume 18, Issue 1, 2011

Since protein function depends on folding, successful development of active pharmaceutical proteins requires in vitro production of functional, properly folded proteins. In vitro protein folding and hence production can be assisted by co-solvents, including osmolytes and arginine. Osmolytes accumulate in the cytoplasm to raise the osmotic pressure against environmental water stresses, resulting in stabilization of proteins. Th Read More

Owing to the serious clinical consequences associated with acquisition of resistance to current antiretroviral drugs, discovery of new drug targets and development of novel anti-HIV-1 therapeutic agents have become a high research priority. The late stages of HIV-1 replication involve the processes of assembly, budding and maturation, and comprise several new potential therapeutic targets which have not (yet) been targ Read More

Currently, there has been considerable interest in the discovery of original molecules with broad-spectrum anti- HIV activity and favourable pharmacokinetic profiles, to be used as an alternative to the approved anti-HIV/AIDS drugs, should they fail as therapeutics. Five-membered azole heterocycles represent an important class of lead structures for novel anti-HIV drug development. They can serve as versatile building b Read More

The metabotropic glutamate type 2 (mGlu2) receptor is a G-protein coupled receptor (GPCR) expressed on presynaptic nerve terminals where it negatively modulates glutamate and GABA release. Mixed mGlu2/mGlu3 orthosteric agonists such as LY354740 have shown activity in a range of preclinical animal models of anxiety and schizophrenia. Clinical work with LY354740 demonstrated activity in a CO2 inhalation study sug Read More

Three xanthine oxidase substrates (i.e., xanthine, adenine, and 2-amino-4-hydroxypterin) show a “substrate inhibition” pattern (i.e., slower turnover rates at higher substrate concentrations), whereas another two substrates (i.e., xanthopterin and lumazine) show a “substrate activation” pattern (i.e., higher turnover rates at higher substrate concentrations). Binding of a 6-formylpterin at one of the two xanthine oxidase active site Read More

Globally, diabetes and obesity are two of the most common metabolic diseases of the 21st century. Increasingly, not only adults but children and adolescents are being affected. New approaches are needed to prevent and treat these disorders and to reduce the impact of associated disease-related complications. Industrial-scale production using plant-root cultures can produce quantities and quality of inexpensive bioactive s Read More

Nicotine dependence (ND) is one of the world's leading causes of preventable death. Nicotine addiction and other forms of drug addiction continue to be significant public health problems in the world. Evidence for a genetic influence on smoking behaviour and ND has prompted a search for susceptibility genes. Evidence has recently accumulated that single nucleotide polymorphisms (SNPs) in the genetic region encoding the Read More

Efforts to develop an effective malaria vaccine are yet to be successful and thus chemotherapy remains the mainstay of malaria control strategy. Plasmodium falciparum, the parasite that causes about 90% of all global malaria cases is increasingly becoming resistant to most antimalarial drugs in clinical use. This dire situation is aggravated by reports from Southeast Asia, of the parasite becoming resistant to the “magic b Read More

Chagas disease is one of the most important endemic diseases in Latin America, caused by Trypanosoma cruzi. The drugs used for the treatment of this disease, nifurtimox and benznidazole, are toxic and present severe side effects. The need of effective drugs, without adverse effects, has stimulated the search for new compounds with potential clinical utility. An overview of a number of natural naphthoquinones tested agai Read More