title: A convenient synthesis of lubeluzole and its enantiomer: evaluation as chemosensitizing agents on human ovarian adenocarcinoma and lung carcinoma cells.
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.
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, via E Orabona 4, 70126 Bari, Italy.
authors.forename: Maria Maddalena
authors.initials: MM
authors.lastname: Cavalluzzi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Viale
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.forename: Alessia
authors.initials: A
authors.lastname: Carocci
authors.forename: Alessia
authors.initials: A
authors.lastname: Catalano
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrieri
authors.forename: Carlo
authors.initials: C
authors.lastname: Franchini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lentini
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D013844:Thiazoles; D004317:Doxorubicin; D017239:Paclitaxel; C097722:lubeluzole
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Antiproliferative activity; CaM; Drug repositioning; Enantiomeric excess; HKR; Hydrolytic kinetic resolution; MTT; NO; NOS; P-glycoprotein; PgP; Synergism; calmodulin; hydrolytic kinetic resolution; nitric oxide; nitric oxide synthase