Document Detail

Design, synthesis and biological evaluation of 3,5-diaryl-isoxazoline/isoxazole-pyrrolobenzodiazepine conjugates as potential anticancer agents.
MedLine Citation:
PMID:  20557981     Owner:  NLM     Status:  MEDLINE    
A series of 3,5-diaryl-isoxazoline/isoxazole linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates were prepared. These conjugates showed potent anticancer activity with GI(50) values in the range of <0.1-3.6 microM. Some of these PBD conjugates (6a-c) with promising anticancer activity were further investigated on the cell cycle distribution. Moreover, these PBD conjugates exhibited G0/G1 arrest, enhancement in the levels of p53 protein as well as mitochondrial-mediated intrinsic pathway, leading to release of cytochrome c, activation of caspase-3, cleavage of PARP and subsequent apoptotic cell death. Hence these PBD conjugates with 6a being the most potent one could be be taken up for preclinical studies either alone or in combination with existing therapies.
Ahmed Kamal; J Surendranadha Reddy; M Janaki Ramaiah; D Dastagiri; E Vijaya Bharathi; M Ameruddin Azhar; Farheen Sultana; S N C V L Pushpavalli; Manika Pal-Bhadra; Aarti Juvekar; Subrata Sen; Surekha Zingde
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-31
Journal Detail:
Title:  European journal of medicinal chemistry     Volume:  45     ISSN:  1768-3254     ISO Abbreviation:  Eur J Med Chem     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-09     Completed Date:  2010-11-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0420510     Medline TA:  Eur J Med Chem     Country:  France    
Other Details:
Languages:  eng     Pagination:  3924-37     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Masson SAS. All rights reserved.
Division of Organic Chemistry, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 607, India.
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MeSH Terms
Antineoplastic Agents / chemical synthesis,  chemistry*,  pharmacology*
Apoptosis / drug effects
Benzodiazepines / chemical synthesis,  chemistry*,  pharmacology*
Cell Cycle Proteins / metabolism
Cell Line, Tumor / drug effects
Cell Proliferation / drug effects
Drug Design*
Gene Expression Regulation, Neoplastic / drug effects
Inhibitory Concentration 50
Isoxazoles / chemical synthesis,  chemistry*,  pharmacology*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Cell Cycle Proteins; 0/Isoxazoles; 12794-10-4/Benzodiazepines

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