Antitumor agents. 207. Design, synthesis, and biological testing of 4beta-anilino-2-fluoro-4'-demethylpodophyllotoxin analogues as cytotoxic and antiviral agents

J Med Chem. 2001 Apr 26;44(9):1422-8. doi: 10.1021/jm000377f.

Abstract

2-Fluoropodophyllotoxin (11) and several 4beta-anilino-2-fluoro-4'-O-demethyl analogues were synthesized and evaluated in both antineoplastic and antiviral assays. These compounds were moderately active against some cancer cell lines, but they were less active than the corresponding nonfluorinated analogues. Compound 11 exhibited the best activity against KB carcinoma with a GI(50) of approximately 30 nM. Most compounds exhibited moderate activity against HCMV with ID(50) and ID(90) values in the range of 1 microM and 4 microM, respectively. Both 9 and 11 showed an unusual 10-fold selectivity for HSV-2 compared to HSV-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Chlorocebus aethiops
  • DNA / chemistry
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Herpesvirus 1, Human / drug effects
  • Herpesvirus 2, Human / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Nucleic Acid Hybridization
  • Podophyllotoxin / analogs & derivatives*
  • Podophyllotoxin / chemical synthesis*
  • Podophyllotoxin / chemistry
  • Podophyllotoxin / pharmacology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • Vero Cells

Substances

  • 2-fluoropodophyllotoxin
  • Antineoplastic Agents
  • Antiviral Agents
  • DNA
  • Podophyllotoxin