title: Straightforward synthesis of a novel ring-fused pyrazole-lactam and in vitro cytotoxic activity on cancer cell lines.
abstract: In this paper a straightforward synthesis of a novel pyrazole derivative is reported. Prominent feature of this synthetic process is a 1,3-Dipolar Cycloaddition of a suitable nitrile imine with an activated α,β-unsaturated lactam to afford directly and regioselectively the corresponding ring-fused pyrazole. Having obtained the central core of the synthetic target, a double stepwise functionalization with a "side chain" characterized by a terminal cyclic aliphatic amine was carried out. This molecular structure was designed to interact strongly with typical biological residues, and indeed it showed potent anticancer capability: in vitro cytotoxicity test on five different cancer cell lines showed interesting IC50 values in the range of 15-60 μM for exposure time of 24-72 h, thus resulting comparable with commercially available and nowadays therapeutically exploited anticancer compounds, such as 5-FU and NVP-BEZ235.
authors.affiliation: Department of Industrial Chemistry "Toso Montanari", University of Bologna, Viale Risorgimento, 40136, Bologna, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bertuzzi
authors.affiliation: Department of Industrial Chemistry "Toso Montanari", University of Bologna, Viale Risorgimento, 40136, Bologna, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Locatelli
authors.affiliation: Istituto di Fisiologia Clinica (IFC), Consiglio Nazionale delle Ricerche (CNR), Siena, Italy; IstitutoToscanoTumori (ITT), Core Research Laboratory (CRL), AOU Senese, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Colecchia
authors.affiliation: IstitutoToscanoTumori (ITT), Core Research Laboratory (CRL), AOU Senese, Italy; Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Calandro
authors.affiliation: Department of Industrial Chemistry "Toso Montanari", University of Bologna, Viale Risorgimento, 40136, Bologna, Italy.
authors.forename: B F
authors.initials: BF
authors.lastname: Bonini
authors.affiliation: Department of Industrial Chemistry "Toso Montanari", University of Bologna, Viale Risorgimento, 40136, Bologna, Italy.
authors.forename: J Z
authors.initials: JZ
authors.lastname: Chandanshive
authors.affiliation: Department of Industrial Chemistry "Toso Montanari", University of Bologna, Viale Risorgimento, 40136, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mazzanti
authors.affiliation: Department of Industrial Chemistry "Toso Montanari", University of Bologna, Viale Risorgimento, 40136, Bologna, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Zani
authors.affiliation: Istituto di Fisiologia Clinica (IFC), Consiglio Nazionale delle Ricerche (CNR), Siena, Italy; IstitutoToscanoTumori (ITT), Core Research Laboratory (CRL), AOU Senese, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Chiariello
authors.affiliation: Department of Industrial Chemistry "Toso Montanari", University of Bologna, Viale Risorgimento, 40136, Bologna, Italy. Electronic address: mauro.comesfranchini@unibo.it.
authors.forename: M
authors.initials: M
authors.lastname: Comes Franchini
mesh_terms: D000598:Amino Acids, Cyclic / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D061565:Cycloaddition Reaction; D015195:Drug Design; D006801:Humans; D007097:Imines / Q000737:chemistry; D007769:Lactams / Q000737:chemistry; D009570:Nitriles / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000598:Amino Acids, Cyclic; D000970:Antineoplastic Agents; D007097:Imines; D007769:Lactams; D009570:Nitriles; D011720:Pyrazoles
keywords: 1,3-Dipolar cycloaddition; Anticancer drug; Lactam; Pyrazole