Current Topics in Medicinal Chemistry - Volume 16, Issue 4, 2016

Metalloproteins have attracted momentous attentions for the treatment of many human diseases, including cancer, HIV, hypertension, etc. This article reviews the progresses that have been made in the field of drug development of metalloprotein inhibitors, putting emphasis on the targets of carbonic anhydrase, histone deacetylase, angiotensin converting enzyme, and HIV-1 integrase. Many other important metalloproteins Read More

Methionine aminopeptidases (MetAPs) are metalloenzymes that cleave the N-terminal methionine from newly synthesized peptides and proteins. These MetAP enzymes are present in bacteria, and knockout experiments have shown that MetAP activity is essential for cell life, suggesting that MetAPs are good antibacterial drug targets. MetAP enzymes are also present in the human host and selectivity is essential. There have Read More

HDAC inhibitors (HDACIs), which can be used to kill cancer cells through inhibiting histone deacetylase activity or altering the structure of chromatin, have emerged as efficacious agents in the treatment of cancer. With SAHA, FK228, belinostat and panobinostat approved by the FDA, displaying satisfying activity in both haematological and solid tumors of various tissues, efforts to create selective HDACIs have been attr Read More

Histone acetyl transferases (HATs) and histone deacetylases (HDACs) are antagonistic enzymes regulating the turnover of histone acetylation thereby governing gene expression in a precise manner. Histone acetylation deregulation caused by aberrant expression of classical HDACs plays a crucial role in tumour onset and progression making these enzymes as striking targets for anticancer drugs and therapy. Small molecule Read More

Integrase (IN) is an essential viral enzyme required for HIV-1 replication, which has been targeted by anti-AIDS therapeutics. Integrase strand transfer inhibitors (INSTIs) represent a new class of antiretroviral agents developed for the treatment of HIV-1 infections. Important structural features that are shared by many INSTIs include a coplanar arrangement of three heteroatoms that chelate two catalytic Mg2+ ions in t Read More

HIV-1 integrase (IN) plays an important role in the life cycle of HIV and is responsible for integration of the virus into the human genome. We present computational approaches used to design novel HIV-1 IN inhibitors. We created an IN inhibitor database by collecting experimental data from the literature. We developed quantitative structure-activity relationship (QSAR) models of HIV-1 IN strand transfer (ST) inhibitors us Read More

Matrix metalloproteinases (MMPs) are zinc enzymes responsible for the degradation of the extracellular matrix. With this function, MMPs are involved in many physiological processes, but also in many pathological states. MMP-13 is implicated in the degradation of type II collagen, the main structural protein of articular cartilage, contributing to the development of osteoarthritis and inflammatory diseases. In the last years, a Read More

The antitumor pharmacological property of flavonoids is correlated with inhibition towards glyoxalase I (GLOI), a critical zinc-enzyme in the methylglyoxal detoxification pathway. In this study, 16 flavonoids were examined, and only baicalein (Ki of 0.183 μM) is identified as a potent in vitro GLOI inhibitor. X-ray crystallographic analysis reveals that baicalein chelates with the catalytic Zn2+ via its characteristic C6/C7 hydroxyl Read More