Overcoming cisplatin resistance: design of novel hydrophobic platinum compounds.
Bibliographic record
Abstract
BACKGROUND: The anticancer activity of cisplatin derives from its ability to crosslink DNA. Cisplatin-resistance is partially caused by enhanced nucleotide excision repair (NER). Major 1,2-intrastrand crosslinks can create a hydrophobic notch at the damage site, which can be specifically bound by damage-recognition proteins, thus shielded from NER-activity. We aimed at preventing resistance by enhancing this mechanism using more hydrophobic platinum compounds. METHODS: We synthesized three platinum analogs with increased hydrophobic characteristics. Performing MTT-assays, the efficacy of cisplatin and the novel agents was compared in a fibroblast and eight brain tumour cell lines. RESULTS: Among the novel compounds, the most hydrophobic molecule, methylpyridineplatinum, was most cytotoxic (LC50 = 5.84 x 10(-5) M), followed by methylpyrazineplatinum, the second most hydrophobic (LC50 = 1.79 x 10(-4) M), and pyridineplatinum (LC50 = 2.76 x 10(-4) M). Overall, cisplatin revealed highest cytotoxicity (LC50 = 8.77 x 10(-6) M). CONCLUSIONS: Comparison of the novel compounds supports the hypothesis that increased hydrophobicity contributes to higher antitumour-activity. Other advantageous characteristics of cisplatin might relate to its remaining highest efficacy.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".