Multidimensional optimization of promising antitumor xanthone derivatives

Carlos M.G. Azevedo, Carlos M.M. Afonso*, Diana Sousa, Raquel T. Lima, M. Helena Vasconcelos, Madalena Pedro, João Barbosa, Arlene G. Corrêa, Salette Reis, Madalena M.M. Pinto

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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 languageEnglish
Pages (from-to)2941-2959
Number of pages19
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number11
DOIs
Publication statusPublished - 1 Jun 2013
Externally publishedYes

Keywords

  • Antitumor
  • Benzopyran
  • Chromans
  • Chromene
  • Lipophilicity
  • Solubility
  • Xanthen-9-ones
  • Xanthones

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