Anti-HIV activities of precisely defined, semirigid, carboxylated alternating copolymers

J Med Chem. 2014 Aug 14;57(15):6354-63. doi: 10.1021/jm401913w. Epub 2014 Jul 25.


Di-tert-butyl (E)-4,4'-stilbenedicarboxylate and tert-butyl 4-vinylbenzoate were copolymerized with maleic anhydride and tert-butyl 4-maleimidobenzoate, individually and respectively. After conversion into polyanions, these four copolymers exhibited activity against four HIV-1 strains: IIIb, BaL, JR-CSF, and 92UG037. For both the IIIb and BaL HIV-1 strains, the lowest IC50 (0.095 and 0.23 μg/mL, respectively) values were obtained with poly(4,4'-stilbenedicarboxylate-alt-maleic acid) (DCSti-alt-MA). For JR-CSF and 92UG037, both tier 2 clinical isolates but different clades, DCSti-alt-MA exhibited the lowest IC50 (0.76 and 0.75 μg/mL, respectively). Although DCSti-alt-MA had the lowest IC50 in μg/mL for each strain, the other copolymers had IC50s less than 2-fold higher. Further, these copolymers achieved high selectivity indices (>100) for these clinical isolates. Polymer rigidity, as measured by the statistical segment length, emerged as a key property when comparing anti-HIV activities with those of other polyanions. A speculative illustration was proposed for possible modes of inhibition.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology
  • HIV-1 / drug effects*
  • HIV-1 / isolation & purification
  • HeLa Cells
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / virology
  • Maleic Anhydrides / chemical synthesis
  • Maleic Anhydrides / chemistry*
  • Maleic Anhydrides / pharmacology
  • Maleimides / chemical synthesis
  • Maleimides / chemistry*
  • Maleimides / pharmacology
  • Polymerization
  • Polyvinyls / chemical synthesis
  • Polyvinyls / chemistry*
  • Polyvinyls / pharmacology
  • Species Specificity
  • Structure-Activity Relationship


  • Anti-HIV Agents
  • Maleic Anhydrides
  • Maleimides
  • Polyvinyls
  • poly((di-tert-butyl 4,4'-stilbenedicarboxylate)-alt-(tert-butyl 4-maleimidobenzoate)
  • poly((di-tert-butyl 4,4'-stilbenedicarboxylate)-alt-maleic anhydride)
  • poly((tert-butyl 4-vinylbenzoate)-alt-(tert-butyl 4-maleimidobenzoate))
  • poly((tert-butyl 4-vinylbenzoate)-alt-maleic anhydride)