Synthesis and multidrug resistance reversal activity of dihydroptychantol A and its novel derivatives.

Abstract

The macrocyclic bisbibenzyl dihydroptychantol A (DHA), previously isolated from Asterella angusta, was synthesized and showed significant multidrug resistance (MDR) reverting activity in chemoresistant cancer cells. In an attempt to discover more potent MDR reversal agents for efficient cancer chemotherapy, DHA derivatives with thiazole rings (19-22) were synthesized, and their cytotoxicities and MDR reversal activities were evaluated in adriamycin-resistant K562/A02, vincristine-resistant KB/VCR and in their parental cells by MTT assays. In response to treatment with each compound, the K562 cell line was the most sensitive, and the vincristine-resistant KB/VCR cell line was the most resistant. Marked decreases in K562 and K562/A02 cell viability were detectable after treatment with the synthesized derivatives of DHA, while less inhibitory effects on cell growth were observed in chemical-resistant KB/VCR and KB cells. Moreover, among the tested compounds, the intermediate 17 and the analogues 19, 20, and 21 showed potent MDR reversal activities and increased vincristine cytotoxicity in KB/VCR cells, with the reversal fold ranges from 10.54 to 13.81 (10microM), which is 3.2-4.3-fold stronger than the natural product DHA.

• Authors: Bin Sun, Hui-qing Yuan, Guang-min Xi, Yu-dao Ma, Hong-xiang Lou
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 17 Issue 14 Pg. 4981-9 (Jul 15 2009) ISSN: 1464-3391 [Electronic] England
• PMID: 19540127 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Phenyl Ethers
• Stilbenes
• Thiazoles
• dihydroptychantol A

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (chemistry, metabolism)
• Animals
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Drug Resistance, Multiple (drug effects)
• Hepatophyta (chemistry)
• Humans
• K562 Cells
• Models, Molecular
• Molecular Conformation
• Murinae
• Phenyl Ethers (chemical synthesis, chemistry, pharmacology)
• Protein Binding
• Stilbenes (chemical synthesis, chemistry, pharmacology)
• Thiazoles (chemical synthesis, chemistry)