Phospholipid analogs against HIV-1 infection and disease.
Phospholipid analogs are a new class of compounds with potent activity against HIV infection when used alone or conjugated with other therapeutic agents. When conjugated to the nucleoside analog AZT, the resulting phospholipid-AZT conjugate can double target the virus replication cycle by inhibiting the viral reverse transcriptase (by AZT) and inducing the production of defective virus particles that lack functional gp120 expression on the virus surface resulting in reduced capacity to bind to CD4+ cells and inhibition of infected cell-cell fusion (by phospholipid). Of great interest are data indicating that selected phospholipids are active against drug resistant variants, a current major problem in treating HIV/AIDS and controlling the epidemic occurring in various parts of the world. The purpose of this review is to provide current information on the design and synthesis of various types of phospholipids and phospholipid conjugates, in-vitro and in-vivo antiviral activity, tissue distribution, intracellular metabolism, and mechanism of action. The future development of this novel class of compounds offers an exciting approach for reducing the toxicity and enhancing the distribution of therapeutic drugs to the lymphatics and central nervous system and suppressing the emergence of drug resistant variants of HIV.
Morris-Natschke
Susan L
SL
School of Pharmacy, The University of North Carolina, Chapel Hill 27599, USA.
Ishaq
Khalid S
KS
Kucera
Louis S
LS
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009705:Nucleosides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010743:Phospholipids / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D014018:Tissue Distribution; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D009705:Nucleosides; D010743:Phospholipids; D011355:Prodrugs