Current Pharmaceutical Design - Volume 11, Issue 29, 2005

The field of developing topical microbicides as preventive agents against HIV is rapidly emerging. This issue of anti-HIV drug design focuses on introducing novel approaches in designing anti-HIV microbicides. The selection of this topic was made with the intention to complement the first two issues of anti-HIV Drug Design (Current Pharmaceutical Sciences, 2002, Volume 8, number 8) and (Current Pharmaceutical Sciences Read More

In the last 50 years, changes in cultural and scientific realities and customs have resulted in a worldwide epidemic of sexually transmitted diseases (STD). This is a multi-factorial problem resulting in part from: 1) an increased permissiveness in sexual attitudes in the Western world that results in earlier onset of intercourse and increased numbers of partners and types of sex acts; 2) a global transportation network that facilitates Read More

The HIV pandemic continues to spread throughout the world, particularly affecting populations in developing countries. Women now comprise half of those infected. Efforts to limit this scourge need to be maximally implemented. A multi-faceted approach, including the research and advance of microbicides - or 'chemical condoms' - offers promise. Microbicides are self-administered, prophylactic products designed to protect aga Read More

Most heterosexual women want to reduce the risk of acquiring a sexually transmitted infection; many also want to control their fertility. Several chemical agents have been proposed to dramatically slow the spread of HIV infections. Ideally, vaginal microbicides, with or without contraceptive properties, should be safe, effective, and affordable for women everywhere. Amphiphiles, which are surfactants that can act as deterge Read More

The HIV-1 epidemic continues to spread at a rate of over 15, 000 new cases daily. HIV-1 transmission through heterosexual contact became the dominant risk for women globally. About half of the over 40 million HIV-1 infected individuals worldwide are now women. The lack of empowerment of women is the fundamental cause for the rampant spread of HIV-1 in women. Topical microbicides applied intravaginally offer an optio Read More

Indolyl aryl sulfones (IASs) are a potent class of NNRTIs developed from L-737,126, a lead agent discovered by Merck AG. IAS derivatives are endowed with inhibitory activities against wt HIV-1 in the low nanomolar concentration range. Introduction of two methyl groups at positions 3 and 5 of the phenyl ring of the aryl sulfonyl moiety furnished IAS derivatives such as 5-chloro- or 5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]in Read More

In the central nervous system (CNS), abnormal deposition of insoluble protein aggregates or inclusion bodies within nerve cells is commonly observed in association with several neurodegenerative diseases. The ubiquitinated protein aggregates are believed to result from malfunction or overload of the ubiquitin-proteasome pathway or from structural changes in the protein substrates which prevent their recognition and Read More

Current interest in studies on tissue distribution stems from the limited capacity to predict tissue concentrations and the pharmacological response from plasma drug levels, and from the limitations - both methodological and deontological- involved in doing so, especially in humans. In this review we carry out a comparative analysis of the methods used for studying tissue distribution, placing special focus on recently developed no Read More

The novel carbocyclic nucleoside, abacavir, is metabolized in cells to carbovir triphosphate which is a potent inhibitor of HIV reverse transcriptase (Ki 0.021 μM with calf thymus DNA template primer). Abacavir exhibits potent in vitro antiviral activity against wild-type HIV-1 (IC50 4.0 μM, MT-4 cells) but this activity is lower than the activity of AZT (IC50 0.040 μM, MT-4 cells). However, there is no significant difference between th Read More