title: Novel chiral ferrocenylpyrazolo[1,5-a][1,4]diazepin-4-one derivatives--synthesis, characterization and inhibition against lung cancer cells.
abstract: A series of novel 2-ferrocenyl-7-hydroxy-5-phenethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepin-4-one derivatives with optical activity (2) was synthesized in the microwave-assisted condition and characterized by means of IR, (1)H NMR and mass spectroscopy, and furthermore confirmed by X-ray analysis of a representative compound (R)-2a. Preliminary biological evaluation showed that some compounds could suppress the growth of A549, H322 and H1299 lung cancer cells. Among the tested compounds, 2b-d were more effective and might perform their action through cell cycle arrest for A549 cell. Whereas these compounds inhibited growth of H1299 and H322 cells by inducing apoptosis. The anti-tumor activities of these compounds were related to the nature of substituents in benzene moiety. In addition, the results indicated also that compounds 2b-d possessed notable cytotoxicity and selectivity for A549 vs H1299 and H322 lung cancer cells.
authors.affiliation: Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Shanda Nanlu 27, Jinan, Shandong 250100, PR China.
authors.forename: Shi-Li
authors.initials: SL
authors.lastname: Shen
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Shao
authors.forename: Ji-Zhuang
authors.initials: JZ
authors.lastname: Luo
authors.forename: Jin-Ting
authors.initials: JT
authors.lastname: Liu
authors.forename: Jun-Ying
authors.initials: JY
authors.lastname: Miao
authors.forename: Bao-Xiang
authors.initials: BX
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001389:Azirines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018360:Crystallography, X-Ray; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D055664:Electrochemical Techniques; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D006860:Hydrogen Bonding; D008175:Lung Neoplasms / Q000473:pathology; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D001381:Azepines; D001389:Azirines; D004095:Dihydropyridines; D005296:Ferrous Compounds; D011720:Pyrazoles; C584611:ferrocenylpyrazolo(1,5-a)(1,4)diazepin-4-one; C069267:diazipine