Tetramethylpiperidine-substitution increases the antitumor activity of the riminophenazines for an acquired multidrug-resistant cell line.

Abstract

The multidrug resistance (MDR)-neutralizing and cytotoxic properties of five tetramethylpiperidine (TMP)-substituted phenazines were compared with those of their corresponding isopropyl-substituted analogues using a P-glycoprotein (P-gp)-expressing small cell lung cancer cell line (H69/LX4). All of the TMP-substituted phenazines tested outperformed their isopropyl analogues with respect to both cytotoxic and chemosensitizing properties, indicating the importance of TMP-substitution when designing novel riminophenazines with increased activity against MDR cancer cell lines. Of the TMP-substituted phenazines tested, B4112, chlorinated at position 3 of the phenyl- and anilino-rings, had the most potent anti-cancer activity in vitro, making this agent a potential candidate for evaluation in experimental and clinical oncology.

• Authors: C E van Rensburg, G K Jooné, J F O'Sullivan
• Journal: Anti-cancer drug design (Anticancer Drug Des) Vol. 15 Issue 4 Pg. 303-6 (Aug 2000) ISSN: 0266-9536 [Print] United States
• PMID: 11200506 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents
• Antineoplastic Agents, Phytogenic
• Phenazines
• Piperidines
• Vinblastine

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (biosynthesis, metabolism)
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Carcinoma, Small Cell (drug therapy, metabolism)
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Humans
• Inhibitory Concentration 50
• Lung Neoplasms (drug therapy, metabolism)
• Phenazines (chemical synthesis, pharmacology)
• Piperidines (chemical synthesis, pharmacology)
• Structure-Activity Relationship
• Tumor Cells, Cultured
• Vinblastine (pharmacology)