Cytotoxicity of cis-Platinum(II) Conjugate Models. The Effect of Chelating Arms and Leaving Groups on Cytotoxicity: A Quantitative Structure−Activity Relationship Approach
| العنوان: | Cytotoxicity of cis-Platinum(II) Conjugate Models. The Effect of Chelating Arms and Leaving Groups on Cytotoxicity: A Quantitative Structure−Activity Relationship Approach |
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| المؤلفون: | Elisabetta Gabano, Alessandro Maiocchi, Elena Caterina Giovanna Monti, Claudio Cassino, Domenico Osella, Marzia B. Gariboldi, Emilio Marengo |
| المصدر: | Journal of Medicinal Chemistry. 48:857-866 |
| بيانات النشر: | American Chemical Society (ACS), 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Models, Molecular, Spectrometry, Mass, Electrospray Ionization, Quantitative structure–activity relationship, Magnetic Resonance Spectroscopy, Organoplatinum Compounds, Stereochemistry, Quantitative Structure-Activity Relationship, Antineoplastic Agents, Inhibitory Concentration 50, chemistry.chemical_compound, Cell Line, Tumor, Molecular descriptor, Drug Discovery, medicine, Humans, Cytotoxicity, Chelating Agents, Cisplatin, Cancer, medicine.disease, Carboplatin, Oxaliplatin, chemistry, Drug Resistance, Neoplasm, Cancer research, Regression Analysis, Molecular Medicine, Drug Screening Assays, Antitumor, medicine.drug, Conjugate |
| الوصف: | Thirteen newly synthesized or resynthesized diamine-platinum(II) complexes were characterized, and their cytotoxic activities (IC50) were tested on parental and resistant ovarian cancer cell lines. They represent models of conjugates between biologically active vectors and cytotoxic Pt(II) moieties within the "drug targeting and delivery strategy". Three drugs, routinely employed in the clinical treatment of cancer, namely, cisplatin, carboplatin, and oxaliplatin, were also included in the study as controls. The quantitative structure-activity relationship approach provides simple regression models able to predict log(1/IC50) of diamine-platinum(II) complexes on both parental and resistant ovarian cancer cell lines. The 16 complexes were characterized using 197 molecular descriptors, after which the best regression models relating a subset of these descriptors to the log(1/IC50) in the two cancer cell lines were calculated. Models with four variables proved to be endowed with very good predictive ability Q2(LMO-50%) > or = 85.6%, making it possible to discard 50% of the molecules from the test set following for cross-validation procedure. A four-variable regression model also proved effective in predicting the resistance index RI, Q2(LMO-50%) = 84.4%. |
| تدمد: | 1520-4804 0022-2623 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e86a7a28ef89c99df636dade52d2367aTest https://doi.org/10.1021/jm049508tTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e86a7a28ef89c99df636dade52d2367a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
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