Abstract
Novel disubstituted adamantyl derivatives were synthesized and evaluated in a P-glycoprotein dependent multidrug resistance cancer cell line. The hit to lead optimization provided potent MDR reversal agents. Some potent adamantyl derivatives were more than 10-fold more potent than verapamil without considerable intrinsic cytotoxicity. The 3-trifluorophenyl derivative 14f did not affect the metabolism of CYP450 3A4, whereas most of MDR revertants had a weak inhibitory effect.
Original language | English |
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Pages (from-to) | 5376-5379 |
Number of pages | 4 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 19 |
Issue number | 18 |
DOIs | |
Publication status | Published - 2009 Sept 15 |
Bibliographical note
Funding Information:This study was supported by KRIBB Research Initiative Program and Korea Science and Engineering Foundation (KOSEF) Grants (2008-05676 and RO1-2008-000-11354-0), South Korea.
Keywords
- ABC transporter
- Adamantane
- CYP3A4
- MES-SA/DX5
- Multidrug resistance
- P-glycoprotein
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry