Current Pharmaceutical Design - Volume 19, Issue 10, 2013

Acquired Immune Deficiency Syndrome (AIDS), an immuno-compromized condition, a sequel to untreated human immunodeficiency virus (HIV) infection, inviting several life-threatening diseases, has become one of the most fatal disorders in the recent past because of HIV strain variance due to mutations, passive latency and reservoirs helping in replenishing and reviving the HIV-1 proviral DNA. Scientific efforts have led to Read More

Since the discovery of human immunodeficiency virus (HIV) as a causative agent of acquired immune deficiency syndrome (AIDS) various strategies were employed to counter its devastating actions. One such concept relies on the prevention of HIV entry into host's “competent” cells by means of compounds known as entry inhibitors. HIV entry inhibitors comprise a group of immensely diverse compounds ranging fro Read More

Fusion of viral and cellular membranes is an essential step for HIV-1 infection. This process offers an attractive target for developing antiviral agents. T20 (Enfuvirtide, Fuzeon), a 36-amino acid peptide derived from the C-terminal heptad repeat region of HIV-1 gp41, is the first and only clinically approved HIV-1 fusion inhibitor that being used for treatment of HIV/AIDS patients failed to respond to current antiretroviral dr Read More

HIV-1 membrane fusion as a part of the process of viral entry in the target cells is facilitated by gp41 and gp120, which are encoded by Env gene of HIV-1. Based on the structure and the mechanism researches, new treatment options targeting HIV-1 entry process have been proposed. Enfuvirtide, which mimics amino acid sequences of viral envelope glycoprotein gp41, is the first HIV-1 fusion inhibitor approved by FDA. Read More

Gp41 is regarded as an attractive target for development of HIV-1 entry inhibitors since it mediates the fusion process of HIV- 1 entry into the target cell through the six-helix bundle (6-HB) formation between its N-heptad repeat (NHR) and C-heptad repeat (CHR). Any chemical entity that disrupts the six-helix bundle formation may inhibit the fusion process, thereby blocking HIV-1 entry into the target cells. A brief review of Read More

Human immunodeficiency virus type 1 (HIV-1) primarily infects and then destroys CD4-positive lymphocytes, leading to the acquired immunodeficiency syndrome (AIDS). Over 20 drugs, most small and orally bioavailable, have been approved, and include reverse transcriptase and protease inhibitors. In 2003, the US-FDA approved enfuvirtide (T-20), a 36-amino acid peptide derived from the C-terminal heptad repea Read More

HIV integrase became an important target for drug development more than twenty years ago. However, progress has been hampered by the lack of assays suitable for high throughput screening, a reliable crystal structure or pharmacophore. Thus, a real breakthrough was only observed in 2007 with the introduction of the first integrase inhibitor, raltegravir, into treatment. To date, the armament of integrase inhibitors is bro Read More

The HIV-1 reverse transcriptase (RT) is one of the most attracting targets for the development of early phase infection inhibitors. Although many RT inhibitors have been approved for the treatment of HIV-1 infection, they all target the polymerase function of this enzyme. So far, no drugs are available for the inhibition of the RT associated ribonuclease H function (RNase H), which plays an essential role in the HIV replication cy Read More

HIV-1 infection can be effectively controlled by HAART, which improves the quality of lives of infected individuals, but fails to completely eradicate the virus, even after decades of treatment. This issue, together with the emergence of multi-drug-resistant viruses, clearly underscores the continuing need to find novel agents able to target vulnerable steps in the viral replication cycle. HIV transcriptional regulation is a cruci Read More

Branched sugar nucleosides have attracted much attention due to their biological activities. We have demonstrated that epoxysugar nucleosides serve as versatile precursor for the stereo-defined synthesis of these nucleoside derivatives on the basis of its ring opening with organoaluminum or organosilicon reagents. In this review article, novel methods for the synthesis of nucleoside analogues branched at the 1' and 4'-positi Read More

Background: A growing body of evidence suggests that glutamatergic system, especially the abnormalities of glutamate and N-methyl-D-aspartate (NMDA) receptors contribute to the pathophysiology of major depressive disorders. An imbalance in glutamatergic neurotransmission may contribute to increased levels of NMDA agonism, thereby enhancing excitatory activity in most brain circuits involved in major depressio Read More

Tubulin protein is a highly imperative and feasible goal for anticancer drug discovery. Hundreds of naturally occurring, semi synthetic and synthetic antitubulin agents have been reported till now. Among these, Combretastatin A - 4 (CA - 4) is effective antimitotic agent possessing potent cytotoxicity against a panel of cancer cells, including multi-drug resistant cancer cell lines. The inadequate water solubility and inactivati Read More

Objective. Rheumatoid arthritis (RA) is a chronic inflammatory disease that damages the synovial joints, and patients with it are often anorexic and cachectic with high morbidity and mortality. Biological therapy with anti-tumor necrosis factor (TNF)-α has been proven effective as a treatment for RA. However, the long-term effects of anti-TNF-α therapy on body weight, appetite, plasma gut hormones and leptin have not been inve Read More