Modulation of human mammary cell sensitivity to paclitaxel by new quinoline sulfonamides

Bioorg Med Chem Lett. 2001 Sep 17;11(18):2457-60. doi: 10.1016/s0960-894x(01)00462-0.

Abstract

Sulfonamide derivatives of chloroquine and primaquine were synthesised and evaluated against both paclitaxel-sensitive and paclitaxel-resistant mammarian cancer cell lines. All derivatives exhibited at least 96% MDR reversal activity when co-administered with paclitaxel at 5 microM. The best compound, a chloroquine derivative, exhibited 99% MDR reversal activity when co-administered with paclitaxel at 1 microM. Molecular modelling studies reveal that these derivatives share a common pharmacophore with taxane MDR reversal agents.

Publication types

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

MeSH terms

  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Breast Neoplasms / drug therapy*
  • Drug Design
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Paclitaxel / pharmacology*
  • Quinolines / chemistry
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antimalarials
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Quinolines
  • Sulfonamides
  • quinoline
  • Paclitaxel