Multidimensional optimization of promising antitumor xanthone derivatives
| Autor: | Carlos A. M. Afonso, Diana Sousa, M. Helena Vasconcelos, João Paulo Peixoto Pena Barbosa, Salette Reis, Arlene G. Corrêa, Madalena Pinto, Carlos M. G. Azevedo, Raquel T. Lima, Madalena Pedro |
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| Rok vydání: | 2013 |
| Předmět: |
Cell Survival
Stereochemistry Xanthones Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Biochemistry Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Drug Discovery Xanthone Humans Structure–activity relationship Solubility Molecular Biology Micelles Liposome Organic Chemistry Combinatorial chemistry Benzopyran Partition coefficient Kinetics chemistry Organ Specificity Drug Design Liposomes Lipophilicity Molecular Medicine Drug Screening Assays Antitumor Derivative (chemistry) |
| Zdroj: | Bioorganic & Medicinal Chemistry. 21:2941-2959 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2013.03.079 |
| Popis: | A promising antitumor xanthone derivative was optimized following a multidimensional approach that involved the synthesis of 17 analogues, the study of their lipophilicity and solubility, and the evaluation of their growth inhibitory activity on four human tumor cell lines. A new synthetic route for the hit xanthone derivative was also developed and applied for the synthesis of its analogues. Among the used cell lines, the HL-60 showed to be in general more sensitive to the compounds tested, with the most potent compound having a GI50 of 5.1 μM, lower than the hit compound. Lipophilicity was evaluated by the partition coefficient (K(p)) of a solute between buffer and two membrane models, namely liposomes and micelles. The compounds showed a logK(p) between 3 and 5 and the two membrane models showed a good correlation (r(2)=0.916) between each other. Studies concerning relationship between solubility and structure were developed for the hit compound and 5 of its analogues. |
| Databáze: | OpenAIRE |
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