Current Medicinal Chemistry - Volume 10, Issue 17, 2003

In the present era, acquired immunodeficiency syndrome (AIDS) is the most fatal disorder for which no completely successful chemotherapy could be developed so far. The pandemic spread of this disease has prompted an unprecedented scientific and clinical effort to understand and combat it. The causative agent of AIDS has been identified as a retrovirus of type 1 (HIV-1). Therefore, a great attention has been focused in the Read More

The replicative cycle of the human immunodeficiency virus (HIV) can be interrupted at several stages. Until recently only the viral reverse transcriptase and protease were the only enzymes targeted by antiretroviral agents. However, the first HIV entry inhibitor (T-20, Enfuvirtide, Fuseon) to be used in humans has been approved by the Food and Drug Administration (FDA). The HIV entry process is considered as an Read More

In recent years, tremendous progress has been made in understanding the HIV- 1 entry process in which the viral and cellular membranes are fused, resulting in the subsequent delivery of the viral genome into the host cell. The mechanistic insight gained from these studies has led to the formulation of exciting new approaches for therapeutic intervention. One of the first and clinically most advanced drugs to emerge from Read More

Beneficial antiviral HIV-1 chemotherapy is associated with adverse reactions. To optimize the desired actions and to lower the side effects of nonnucleoside HIV-1 reverse transcriptase (RT) inhibitors (NNRTIs), quantitative structure-activity relationships (QSARs) were studied by using a series of HEPT derivatives of NNRTIs. Hypothesis testing requires that certain assumptions are approximately satisfied in statistically bas Read More

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as TIBO, HEPT and dipyridodiazepinone are effective against HIV-1 RT. These NNRTIs are chemically and structurally diverse, but they all bind to a common allosteric site of HIV-1 RT. These inhibitors exhibit high potency, low cytotoxicity and produce few side effects. However, the emergency of drug-resistance viral strain has limited the therapeutic efficiency Read More

An excellent example in the field of rational drug design is the discovery and development of more than a dozen drugs for the treatment of AIDS. The major targets for the development of new chemotherapeutic agents are Reverse Transcriptase and Protease, the enzymes encoded by HIV-1. The introduction of HIV-1 protease (HIV-1 PR) inhibitors, in particular, has drastically decreased the mortality and morbidity associated w Read More

HIV is the most significant risk factor for many opportunistic infections like fungal, tuberculosis, etc. The intense media coverage of AIDS puts the public on an emotional roller caster, and inflated promises are engendered by each success. For the moment drugs acting as both HIV-reverse transcriptase inhibitors along with antimicrobial properties are one of the brightest hope. The Non-nucleoside reverse transcriptase inhib Read More

Tubulin protein is a major target for anticancer drug discovery. As a result, antimitotic agents constitute an important class of the current anticancer drugs. Hundreds of tubulin inhibitors, naturally occurring, semisynthetic or synthetic, have been reported. Among these, combretastatin A-4 (CA-4), isolated from a South African tree Combretum caffrum, is one of the most potent antimitotic agents. CA-4 shows strong cyto Read More

The isoprostanes are a unique series of prostaglandin-like compounds formed in vivo from the free radical-catalyzed peroxidation of arachidonic acid independent of the cyclooxygenase enzyme. The purpose of this article is to summarize our knowledge regarding the isoprostanes and discuss what are avenues for future research. Novel aspects related to the biochemistry of isoprostane formation and methods by which these Read More

The majority of nonantibacterial activities discovered for β-lactam derivatives during the last 15 years are based on their ability to form a stable covalent complex with nucleophile in the active site of enzymes regulating fundamental physiological processes in mammalian organism such as serine and cysteine proteases, LDL phospholipase A2, A-independent transacylase and some still indeciphered enzymes. Regulation of th Read More

A growing body of evidence has shown that oxidative stress may be involved in the development of vascular complications associated with diabetes. However, the molecular mechanism for increased reactive oxygen species (ROS) production in diabetes remains uncertain. Among various possible mechanisms, attention have increasingly been paid to NAD(P)H oxidase as the most important source of ROS productio Read More