Fullerene derivatives as dual inhibitors of HIV-1 reverse transcriptase and protease

Bioorg Med Chem Lett. 2021 Jan 1:31:127675. doi: 10.1016/j.bmcl.2020.127675. Epub 2020 Nov 5.

Abstract

In the present study, we newly synthesized three types of novel fullerene derivatives: pyridinium-type derivatives trans-3a and 4a-5b, piperidinium-type derivative 9, and proline-type derivatives 10a-12. Among the assessed compounds, 5a, 10e, 10f, 10i, 11a-d, and 12 were found to inhibit both HIV reverse transcriptase and HIV protease (HIV-PR), with IC50 values in the low micromolar range being observed. Regarding HIV-PR inhibition activity, proline-type derivatives 11a-11d and 12, bearing an alkyl chain between the hydroxylmethylcarbonyl (HMC) moiety and pyrrolidine ring, were more potent than other derivatives. This result might indicate that connecting HMC moieties with proline-type fullerene derivatives through properly sized alkyl chain leads to improved HIV-PR inhibitory activity.

Keywords: Fullerene; HIV protease; HIV reverse transcriptase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Fullerenes / chemistry
  • Fullerenes / pharmacology*
  • HIV Protease / metabolism*
  • HIV Protease Inhibitors / chemical synthesis
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / pharmacology*
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • Molecular Structure
  • Pyridinium Compounds / chemistry
  • Pyridinium Compounds / pharmacology*
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Fullerenes
  • HIV Protease Inhibitors
  • Pyridinium Compounds
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • HIV Protease