title: Original research paper. Hydrazinyldiene-chroman-2,4-diones in inducing growth arrest and apoptosis in breast cancer cells: Synergism with doxorubicin and correlation with physicochemical properties.
abstract: This study evaluates the effects of previously synthesized hydrazinyldiene-chroman-2,4-diones on cell proliferation and apoptosis, cell cycle distribution and migration capacity of MCF-7 breast cancer cells in synergy with doxorubicin. Physicochemical properties of the synthesized compounds were correlated with their structure and activity. Significant cell viability decrease in comparison with the effect of doxorubicin alone and the reference 4-hydroxycoumarin was observed when combination treatment comprising doxorubicin and the title compounds was applied. Synergistic effect with doxorubicin was also observed in down-regulation of phospho-Thr308Akt levels, confirming reduced proliferation and increased apoptosis. Combined treatment increased the percentage of cells arrested at the G2/M stage. Additive inhibition of cell migration was also observed, pointing to the possibility of reducing the risk of metastases. With their solubility profile and log D7.4, all the synthesized compounds follow Lipinski's rule of five for good permeability (absorption) potential.
authors.forename: Lulzime
authors.initials: L
authors.lastname: Ballazhi
authors.forename: Faik
authors.initials: F
authors.lastname: Imeri
authors.forename: Ahmed
authors.initials: A
authors.lastname: Jashari
authors.forename: Emil
authors.initials: E
authors.lastname: Popovski
authors.forename: Goran
authors.initials: G
authors.lastname: Stojković
authors.forename: Aleksandar J
authors.initials: AJ
authors.lastname: Dimovski
authors.forename: Bozhana
authors.initials: B
authors.lastname: Mikhova
authors.forename: Kristina
authors.initials: K
authors.lastname: Mladenovska
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D015195:Drug Design; D004357:Drug Synergism; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D015394:Molecular Structure; D010539:Permeability; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D004317:Doxorubicin; D051057:Proto-Oncogene Proteins c-akt