Anti-tumor activity of a new series of benzoxazepine derivatives in breast cancer.
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.
Samanta
Krishnananda
K
Endocrinology, Central Drug Research Institute, Lucknow 226 001, UP, India.
Chakravarti
Bandana
B
Mishra
Jitendra Kumar
JK
Dwivedi
Shailendra Kumar Dhar
SK
Nayak
Lakshma Vadithe
LV
Choudhry
Preeti
P
Bid
Hemant Kumar
HK
Konwar
Rituraj
R
Chattopadhyay
Naibedya
N
Panda
Gautam
G
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
D017607:Aluminum Compounds; D000970:Antineoplastic Agents; D018020:Lithium Compounds; D010077:Oxazepines; D013629:Tamoxifen; C042073:lithium aluminum hydride