Abstract
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 (Kp) of a solute between buffer and two membrane models, namely liposomes and micelles. The compounds showed a log Kp between 3 and 5 and the two membrane models showed a good correlation (r2 = 0.916) between each other. Studies concerning relationship between solubility and structure were developed for the hit compound and 5 of its analogues.
Original language | English |
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Pages (from-to) | 2941-2959 |
Number of pages | 19 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 21 |
Issue number | 11 |
DOIs | |
Publication status | Published - 1 Jun 2013 |
Externally published | Yes |
Keywords
- Antitumor
- Benzopyran
- Chromans
- Chromene
- Lipophilicity
- Solubility
- Xanthen-9-ones
- Xanthones