title: Synthesis and antiproliferative activity of a natural like glycoconjugate polycyclic compound.
abstract: A natural like O-glycoconjugate polycyclic compound 4 was obtained by a multistep procedure starting from N-(3-methyl-1-(4-nitrophenyl)-1H-pyrazol-5-yl)acetamide. The glycosyl derivative 4 showed antiproliferative activity against all the tumoral cell lines of the NCI panel in the range 0.47-5.43 μM. Cytofluorimetric analysis performed on MDA-MB231, a very aggressive breast cancer cell line, which does not express estrogen, progesterone and HER-2/neu receptors, showed that 4 is able to induce prolonged cell cycle arrest at G2/M phase and morphological signs of differentiation. These events are correlated with down-regulation of both cyclin B1 and cdc2, the cyclins involved in G2/M transition, as well as up-regulation of cyclin-dependent kinase (CDK) inhibitor p21 Cip1/Waf1.
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Medicinal Chemistry and Pharmaceutical Technologies Section, University of Palermo, Via Archirafi 32, 90123, Palermo, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Maggio
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Medicinal Chemistry and Pharmaceutical Technologies Section, University of Palermo, Via Archirafi 32, 90123, Palermo, Italy.
authors.forename: Maria Valeria
authors.initials: MV
authors.lastname: Raimondi
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Medicinal Chemistry and Pharmaceutical Technologies Section, University of Palermo, Via Archirafi 32, 90123, Palermo, Italy.
authors.forename: Demetrio
authors.initials: D
authors.lastname: Raffa
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Medicinal Chemistry and Pharmaceutical Technologies Section, University of Palermo, Via Archirafi 32, 90123, Palermo, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Plescia
authors.affiliation: ICMMO, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 91405, Orsaycedex, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Scherrmann
authors.affiliation: ICMMO, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 91405, Orsaycedex, France.
authors.forename: Nicolò
authors.initials: N
authors.lastname: Prosa
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, Laboratory of Biochemistry, University of Palermo, 90127, Palermo, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Lauricella
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Laboratory of Biochemistry, University of Palermo, 90127, Palermo, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: D'Anneo
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Medicinal Chemistry and Pharmaceutical Technologies Section, University of Palermo, Via Archirafi 32, 90123, Palermo, Italy. Electronic address: giuseppe.daidone@unipa.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Daidone
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006001:Glycoconjugates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D011083:Polycyclic Compounds / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D006001:Glycoconjugates; D011083:Polycyclic Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone
keywords: Antiproliferative activity; G2/M phase arrest; MDA-MB231; O-glycoconjugate polycyclic compound; Pyrazolo[3,4-b]pyrazolo[3′,4′:2,3]azepino[4,5-f]azocine; p21WAF1 inhibitor