Editorial [Hot Topic: Novel Approaches in Designing Anti-HIV Microbicides and Anti-HIV Agents (Executive Editor: Keykavous Parang)]

摘要

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, 2003, Volume 9, number 22). Additionally several strategies in designing non-nucleoside reverse transcriptase inhibitors (NNRTIs) that can have applications as microbicides are discussed in the last review article.nnMicrobicides are anti-infective prophylactic agents formulated for topical self-administration prior to intercourse to protect against sexually transmitted pathogens such as HIV-1. The article by Mary K. Howett and Jeffrey P. Kuhl summarizes the concept and ideal design of microbicides, principles of microbicide mechanisms, and major types of microbicides such as nonoxynol 9, antibodies and monoclonal antibodies, peptides, high molecular weight charged polymers, entry and fusion inhibitors, and alkyl sulfates.nnThe review by Pomerantz and his colleagues summarizes some of the important products such as BufferGel, Acidform, nonoxynol 9, sodium lauryl sulfate, sodium dodecyl sulfate, C31G, sulfate esters of polysaccacharides, Carrageenan, PRO- 2000, cellulose acetate phthalate, dendrimers, proteins, and NNRTIs, currently in developments stages as HIV microbicides.nnAmphiphiles are surfactant agents that have been investigated as microbicides due to their broad-spectrum of activity and fastacting effect, but they disrupt cell membranes such as epithelial cells and normal vagina flora. The review by Richard D. Gandour discusses amphiphilic acylcarnitine analogues such as Z-14 and Z-15 that may have applications as non-irritating topical microbicides.nnAlkylureas have been introduced as protein denaturing agents that irreversibly disrupt free and intracellular HIV-1 with a wide margin of safety. These compounds are also spermicidal above their virucidal concentration without mucosal toxicity. The review by Arye Rubinstein discusses the anti-HIV 1 properties of alkylureas, their effect on peripheral blood mononuclear cells and epithelial cell viability, mechanism of action, and their toxicological studiesnnIndolyl aryl sulfones (IASs) have been introduced as potent non-nucleoside reverse transcriptase inhibitors against wt HIV-1 and resistant mutants. In a comprehensive review, Dr. Silvestri and his colleague discuss the latest developments in designing novel IASs.nnI would like to thank all of the authors for their valuable contributions to this issue. Without their dedication, the publication of this issue would not have been possible.nnReferencesnn[1] Howett, M. K., Kuhl, J. P. Microbicides for Prevention of Transmission of Sexually Transmitted Diseases. Curr Pharm Design 2005; 11(29): 3731-3746.nn[2] Scholand, S. J., DeSimone, J. A., Pomerantz, R. J. Anti-HIV-1 Microbicides - 'Chemical Condoms' Designed to Limit the Scourge of the HIV-1 Pandemic. Curr Pharm Design 2005; 11(29): 3747-3756.nn[3] Gandour, R. A. Toward a Design of Affordable, Topical Microbicide: Acylcarnitine Analogues. Curr Pharm Design 2005; 11(29): 3757-3767.nn[4] Rubinstein, A. Preclinical Studies of Alkylureas as Anti-HIV Contraceptive and Non-Contraceptive Vaginal Microbicides. Curr Pharm Design 2005; 11(29): 3769-3778.nn[5] Silvestri, R., Artico, M. Indolyl Aryl Sulfones (IASs): Development of Highly Potent NNRTIs Active Against wt-HIV-1 and Clinically Relevant Drug Resistant Mutants. Curr Pharm Design 2005; 11(29): 3779-3806.