6533b833fe1ef96bd129c41c

RESEARCH PRODUCT

Synthesis and antiproliferative activity of a natural like glycoconjugate polycyclic compound

Antonella D’anneoMarie-christine ScherrmannMarianna LauricellaDemetrio RaffaFabiana PlesciaBenedetta MaggioNicolò ProsaMaria Valeria RaimondiGiuseppe Daidone

subject

0301 basic medicineCell cycle checkpointCell SurvivalReceptor ErbB-2StereochemistryGlycoconjugateAntineoplastic AgentsAntiproliferative activityChemistry Techniques Synthetic03 medical and health sciences0302 clinical medicineCyclin-dependent kinaseCell Line TumorDrug DiscoveryHumansPolycyclic CompoundsMDA-MB231Cyclin B1Cell ProliferationCyclinPharmacologychemistry.chemical_classificationBiological ProductsCyclin-dependent kinase 1G2/M phase arrestp21WAF1 inhibitorbiologyChemistryKinaseDrug Discovery3003 Pharmaceutical ScienceO-glycoconjugate polycyclic compoundOrganic ChemistryGeneral MedicineMolecular biologyG2 Phase Cell Cycle CheckpointsGene Expression Regulation Neoplastic030104 developmental biologyCell culturePyrazolo[34-b]pyrazolo[3′4′:23]azepino[45-f]azocineDrug Design030220 oncology & carcinogenesisbiology.proteinM Phase Cell Cycle CheckpointsReceptors ProgesteroneGlycoconjugates

description

Abstract A natural like O -glycoconjugate polycyclic compound 4 was obtained by a multistep procedure starting from N -(3-methyl-1-(4-nitrophenyl)-1 H -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  μ M. 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.

yearjournalcountryeditionlanguage
2016-03-24European Journal of Medicinal Chemistry
https://doi.org/10.1016/j.ejmech.2016.06.027