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Platinum-folate compounds: synthesis, properties and biological activity
K S Vitols1, Y Montejano, T Duffy
1Department of Basic and Clinical Research, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Advances in Enzyme Regulation
|January 1, 1987
Summary
Cisplatin
Area of Science:
- Biochemistry
- Pharmacology
- Cell Biology
Background:
- Cisplatin is a widely used anticancer drug.
- Tetrahydrofolate is essential for cellular processes.
- The interaction between Cisplatin and folates is not fully understood.
Purpose of the Study:
- To investigate the chemical interaction between Cisplatin and tetrahydrofolate.
- To determine the biological implications of this interaction in cancer cells.
Main Methods:
- Spectrophotometry to monitor complex formation.
- TLC and HPLC for purity assessment.
- NMR and elemental analysis for structural elucidation.
- Cell culture (L1210) and HPLC for intracellular folate analysis.
Main Results:
- A stable platinum-tetrahydrofolate complex was formed, with platinum bridging N-5 and N-10 positions.
- Complexation occurred with reduced folates (e.g., 5-methyltetrahydrofolate, Methotrexate) but not with folate or 7,8-dihydrofolate.
- Cisplatin treatment of L1210 cells altered intracellular folate levels, decreasing 5,10-methenyltetrahydrofolate and increasing formylated folates.
- The platinum-tetrahydrofolate complex inhibited dihydrofolate reductase and folate transport in L1210 cells.
Conclusions:
- Cisplatin can chemically interact with tetrahydrofolate and other reduced folates.
- These interactions may influence folate metabolism and Cisplatin's efficacy.
- The platinum-tetrahydrofolate complex exhibits inhibitory activity against key folate pathway enzymes and transporters.