A convenient synthesis of lubeluzole and its enantiomer: Evaluation as chemosensitizing agents on human ovarian adenocarcinoma and lung carcinoma cells |
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Authors: | Maria Maddalena Cavalluzzi Maurizio Viale Claudio Bruno Alessia Carocci Alessia Catalano Antonio Carrieri Carlo Franchini Giovanni Lentini |
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Institution: | 1. Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari ‘Aldo Moro’, via E. Orabona 4, 70126 Bari, Italy;2. IRCCS Azienda Ospedaliera Universitaria San Martino, IST Istituto Nazionale per la Ricerca sul Cancro (IRCCS SMIST), U.O.C. Terapia Immunologia, L.go R. Benzi 10, 16132 Genova, Italy |
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Abstract: | Lubeluzole, a neuroprotective anti-ischemic drug, and its enantiomer were prepared following a convenient procedure based on hydrolytic kinetic resolution. The ee values were >99% and 96%, respectively, as assessed by HPLC analysis. The chemosensitizing effects of both enantiomers were evaluated in combination with either doxorubicin (human ovarian adenocarcinoma A2780 cells) or paclitaxel (human lung carcinoma A549 cells) by the MTT assay. At the lowest concentrations used, lubeluzole showed an overall and remarkable tendency to synergize with both anticancer drugs. In ovarian cancer cells a clear prevalence of antagonistic effect was observed for the R-enantiomer. The synergistic effects of lubeluzole for both drugs were observed over a wide concentration window (0.005–5 μM), the lowest limit being at least 40 times lower than human plasma concentrations previously reported as causing serious side effects. |
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Keywords: | Hydrolytic kinetic resolution Enantiomeric excess Antiproliferative activity Synergism Drug repositioning |
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