Cocrystals of quercetin: synthesis, characterization, and screening of biological activity
Cocrystallization of quercetin with 22 cocrystal formers, i.e. phenolic acids, proline, urea, N-acetylcytosine, carnitine, dacarbazine, diflunisal, kojic acid, lactamide, baclofen, pyrazole, edaravone, salicylamide, O-acetylsalicylamide, 2-imidazolidinone, allopurinol, dipyridamole, 5-sulfosalicylic acid, and 4-sulfobenzoic acid resulted in cocrystals with various stoichiometric ratios. The cocrystals were characterized by FT-IR, DSC, and XRPD. Some of them were non-hygroscopic and stable to thermal stress. The cocrystals quercetin:pyrazole (1:1), quercetin:imidazolidinone (1:1), and quercetin:baclofen (1:2) were found to be stable at various relative humidity conditions at 20–40 °C for up to 3 months. The in vitro antioxidant activity, cytotoxicity, and serine protease inhibitory activity were tested. The best inhibitory activity to pathophysiological proteases was observed for cocrystals with N-acetylcytosine, carnitine, and kojic acid; these cocrystals were the most potent inhibitors of thrombin. About two times better cytotoxic activity to human cervical cancer cells (HeLa) and human colon cancer cells (Caco-2) in comparison with quercetin itself was observed for quercetin:kojic acid (2:1).
KeywordsSolid phase synthesis Drug research Nutraceutical Cytotoxicity Serine protease inhibitory activity Antioxidant activity
This investigation was supported by the Slovak Research and Development Agency, Grant No. APVV-121-2009 and The Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic for the Structural Funds of EU ITMS 26240220040 (M. Veverka, J. Gallovič, E. Švajdlenka).
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