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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Aminopyridines, Antineoplastic Agents, Binding Sites, Brain Neoplasms, Cell Survival, DNA, Dose-Response Relationship, Drug, Fibroblasts, Glioma, Humans, Models, Chemical, Organoplatinum Compounds, Plasmids, Platinum Compounds, Pyridines, Time Factors, Tumor Cells, Cultured.
user
Does cellular accumulation determine the activity of three novel tricyclic platinum agents? Context: Cisplatin (CDDP) is a very useful chemotherapeutic agent, but cellular resistance limits its efficacy in malignant glioma. In order to analyze and overcome this resistance, we synthesized three novel platinum compounds; aminoplatin, methylplatin and oxiplatin, using tricyclic DNA intercalating molecules as models. The novel compounds differ only in one chemical group, which is positioned opposite to the DNA binding site. DNA binding, cellular penetration, and cytotoxicity were compared in three human glioma cell lines (T98G, U87-MG, and U25 IN) and a human fibroblast cell strain (HS 68). 2 Binding to isolated DNA was most effective in aminoplatin, followed by methylplatin and oxiplatin. It differed by factors I. I, 0.35, 0.23, from the DNA binding of CDDP (factor I) for the three compounds, respectively. The cellular penetration, however, was fastest with oxiplatin (factor 10.1) followed by CDDP (1), aminoplatin (0.55), and methylplatin (0.27). The cytotoxicity of the three novel compounds followed the pattern of their cellular penetration with oxiplatin being the most active. U87-MG cells were resistant to CDDP, and in this cell line oxiplatin was more effective than CDDP in overcoming the resistance.
assistant
This indicates cellular penetration to be an important feature and the ketogroup of oxiplatin to be beneficial in tricyclic platinum compounds. Final Decision: yes