title: Anti-tumor activity of a new series of benzoxazepine derivatives in breast cancer.
abstract: A series of new benzoxazepine derivatives substituted with different alkoxy and aryloxy group were synthesized comprising synthetic steps of Mitsunobu reaction, lithium aluminum hydride (LAH) reduction, followed by debenzylation and finally intramolecular Mitsunobu cyclization. The new benzoxazepines specifically inhibited growth of breast cancer cell lines, MCF-7 and MDA-MB-231, but lack cytotoxicity to normal HEK-293 cells. The cell growth inhibition induced by the active compounds was due to cell cycle arrest at G(0)/G(1) phase. The active compound could cause significant reduction in tumor volume of MCF-7 xenograft tumor in nude mice model and their activity was comparable to that of tamoxifen citrate at 16mgkg(-1) dose at 30days of treatment. The identified most active compounds of the series have specific advantages as anti-cancer agent in breast cancer than tamoxifen.
authors.affiliation: Endocrinology, Central Drug Research Institute, Lucknow 226 001, UP, India.
authors.forename: Krishnananda
authors.initials: K
authors.lastname: Samanta
authors.forename: Bandana
authors.initials: B
authors.lastname: Chakravarti
authors.forename: Jitendra Kumar
authors.initials: JK
authors.lastname: Mishra
authors.forename: Shailendra Kumar Dhar
authors.initials: SK
authors.lastname: Dwivedi
authors.forename: Lakshma Vadithe
authors.initials: LV
authors.lastname: Nayak
authors.forename: Preeti
authors.initials: P
authors.lastname: Choudhry
authors.forename: Hemant Kumar
authors.initials: HK
authors.lastname: Bid
authors.forename: Rituraj
authors.initials: R
authors.lastname: Konwar
authors.forename: Naibedya
authors.initials: N
authors.lastname: Chattopadhyay
authors.forename: Gautam
authors.initials: G
authors.lastname: Panda
mesh_terms: D017607:Aluminum Compounds / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003500:Cyclization; D005260:Female; D016193:G1 Phase; D006801:Humans; D018020:Lithium Compounds / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D010077:Oxazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D016192:Resting Phase, Cell Cycle; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D017607:Aluminum Compounds; D000970:Antineoplastic Agents; D018020:Lithium Compounds; D010077:Oxazepines; D013629:Tamoxifen; C042073:lithium aluminum hydride