title: TSAO compounds: the comprehensive story of a unique family of HIV-1 specific inhibitors of reverse transcriptase.
abstract: Emergence of drug-resistant viral strains is one of the major milestones and the main cause for the failure of antiretroviral therapy. Combination of different anti-HIV agents has become the standard clinical practice to keep the viral load at low or even undetectable levels and to prevent emergence of virus-drug resistance. Among the human immunodeficiency virus (HIV) reverse transcriptase (RT) inhibitors, the so called nonnucleoside RT inhibitors (NNRTIs) have gained a definitive place in the treatment of HIV infections in combination with nucleoside analogue RT inhibitors (NRTIs) and HIV protease inhibitors (PIs). The virus can be markedly suppressed for a relatively long period of time when exposed to multiple drug combination therapy (highly active antiretroviral therapy, HAART). TSAO derivatives are a peculiar group of highly functionalized nucleosides that belong to the so-called nonnucleoside RT inhibitors (NNRTIs). They exert their unique selectivity for HIV-1 through a specific interaction with the p51 subunit of HIV-1 RT. They are the first small molecules that seem to interfere with the dimerization process of the enzyme. This review covers the work carried out with this unique class of specific inhibitors of HIV-1 reverse transcriptase, including structure activity relationship studies (SAR), its mechanism of action, resistance studies, model of interaction with the enzyme, etc.
authors.affiliation: Instituto de Química Médica (C.S.I.C.), Juan de la Cierva 3, 28006 Madrid, Spain. mj.camarasa@iqm.csic.es
authors.forename: María-José
authors.initials: MJ
authors.lastname: Camarasa
authors.forename: Ana
authors.initials: A
authors.lastname: San-Félix
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Velázquez
authors.forename: María-Jesús
authors.initials: MJ
authors.lastname: Pérez-Pérez
authors.forename: Federico
authors.initials: F
authors.lastname: Gago
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D015394:Molecular Structure; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D013141:Spiro Compounds; D054303:HIV Reverse Transcriptase