Current Medicinal Chemistry - Volume 18, Issue 16, 2011

The signal transducers and activators of transcription (STATs) include a class of cytoplasmic signaling proteins whose role in the regulation of cell growth and survival is mediated by phosphorylation of a critical tyrosine residue within the STAT protein. This occurs in response to cytokines and growth factors modulating the expression of specific target genes. In particular, phosphorylation induces STAT:STAT dimer formation bet Read More

HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) bind to an allosteric site on reverse transcriptase (RT) and are a key component of highly active anti-retroviral therapy (HAART) combination regimen for clinical treatment of HIV/AIDS. However, the rapid emergence of drug resistance has limited NNRTIs' clinical option. Therefore, there is an urgent need for the design and development of new and safe NNRTI Read More

Clopidogrel is a thienopyridine, which inhibits the platelet P2Y adenosine diphosphate (ADP) receptor termed P2Y12. It is taken as a prodrug that requires biotransformation to an active metabolite by cytochrome P450 (CYP) isoenzymes. In addition, esterases shunt the majority of clopidogrel to an inactive pathway, whilst the remaining prodrug requires two separate CYP-dependent oxidative steps. PPIs might diminish the anti Read More

Mycoses are still one of the most problematic illnesses worldwide, especially affecting immunocompromised individuals. The development of novel antifungal drugs is becoming more demanding every day, since existing drugs either have too many side effects or they tend to lose effectiveness due to the resistant fungal strains. In this scenario, Candida albicans is still the main fungal pathogen isolated in hospitals. Pathogenicity Read More

Protein-protein interactions play a major role in almost all biological pathways and thus, these interactions have a profound impact on the pathogenesis of diseases. The ability to modulate protein-protein interactions with small molecules is an important and rapidly growing area in the field of medicinal chemistry. One of the most common secondary protein structures that are involved in protein-protein interactions are Read More

Combinatorial peptide libraries from synthetic or biological sources have been largely used in the last two-decades with the aim of identifying bioactive peptides that specifically bind proteins and modulate their interactions with other protein partners. Differently from biological libraries, synthetic methods allow the development of different kinds of libraries based on two main characteristics: i) the use of building blocks a Read More

Derivatives of muramyl dipeptide (MDP) are considered as immunostimulants and adjuvants in the immunotherapy of cancer and infections. The interest in these compounds is mainly related to a high variety of their structure and biological properties. Here, we describe the synthesis and biological activity of several recently developed classes of MDP analogues. We also report potential of these analogues in the treatment Read More

It is becoming increasingly clearer that the clinical manifestations of Alzheimer's disease (AD) are not only associated with regional grey matter (GM) damage, but also with abnormal integration between cortical brain regions by disconnection mechanism. This concept comes from the evidence that white matter (WM) damage (as assessed by diffusion MR imaging) can be observed in patients with AD since the early clini Read More

A common characteristic of neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD) is the accumulation of protein aggregates. This reflects a severe disturbance of protein homeostasis, the proteostasis. Here, we review the involvement of the two major proteolytic machineries, the ubiquitin proteasome system (UPS) and the autophagy/lysosomal system, in the pathogen Read More

Parkin functions as an E3 ubiquitin ligase that monoubiquitylates and polyubiquitylates proteins to regulate a variety of cellular processes. It appears that parkin functions as a multipurpose neuroprotectant in a number of toxic paradigms, and loss of parkin's E3 ligase activity seems to play a pathogenic role in both inherited and sporadic Parkinson's disease (PD). Increasing evidence indicates that posttranslational modif Read More

Photodynamic therapy (PDT) involves the administration of a photosensitizer (PS) followed by illumination with visible light, leading to generation of reactive oxygen species. The mechanisms of resistance to PDT ascribed to the PS may be shared with the general mechanisms of drug resistance, and are related to altered drug uptake and efflux rates or altered intracellular trafficking. As a second step, an increased inactivation of Read More