Symmetry-based inhibitors of HIV-1 protease. Design, synthesis and preliminary structure-activity studies of acylated 2,3-diamino-1- hydroxypropanes and 2,4 diamino-1-hydroxybutanes

Mauro Marastoni, Martina Bazzaro, Fabrizio Bortolotti, Severo Salvadori, Roberto Tomatis

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Two series of peptidomimetics containing a novel C2 pseudosymmetrical hydroxyalkyldiamino core structure were prepared from amino acid starting materials and tested for inhibitory activity against the HIV-1 protease (HIV- 1 Pt) and the virus in cell culture. In the 2,3-diamino-1-hydroxypropane series, compound 6a, containing P1/P1(I) benzyl and P2/P2(I) Fmoc substituents, displayed modest HIV-1 Pr inhibition (IC50 = 430 nM). The corresponding 2,4-diamino-1-hydroxybutane derivative (6b) was the best inhibitor of the series (IC50 = 160 nM). Interestingly, 6a and 6b showed satisfactory inhibition of HIV replication in cell culture. (ED50 = 340 and 110 nM, respectively), a result which suggests good cell membrane penetration by this class of compounds.

Original languageEnglish (US)
Pages (from-to)651-657
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume34
Issue number7-8
DOIs
StatePublished - Jul 1999
Externally publishedYes

Keywords

  • Aspartyl protease
  • HIV-1 inhibitors
  • Peptidomimetic

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