Document Detail


Synthesis, anticancer activity and mitochondrial mediated apoptosis inducing ability of 2,5-diaryloxadiazole-pyrrolobenzodiazepine conjugates.
MedLine Citation:
PMID:  20732817     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A series of 2,5-diaryloxadiazole linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates have been prepared and evaluated for their anticancer activity. These conjugates have shown promising activity with GI50 values ranging from <0.1 to 0.29 microM. It is observed that some of these conjugates particularly 4a, 4d, 4i and 4l exhibit significant anticancer activity. Some detailed biological assays relating to the cell cycle aspects associated to Bax and caspases have been examined with a view to understand the mechanism of action of these conjugates.
Authors:
Ahmed Kamal; D Dastagiri; M Janaki Ramaiah; E Vijaya Bharathi; J Surendranadha Reddy; G Balakishan; Pranjal Sarma; S N C V L Pushpavalli; Manika Pal-Bhadra; Aarti Juvekar; Subrata Sen; Surekha Zingde
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-01
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  18     ISSN:  1464-3391     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-06     Completed Date:  2010-12-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  6666-77     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Chemical Biology Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 607, India. ahmedkamal@iict.res.in
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / chemical synthesis*,  chemistry,  therapeutic use
Apoptosis*
Benzodiazepines / chemical synthesis,  chemistry*,  therapeutic use
Caspases / metabolism
Cell Cycle / drug effects
Cell Line, Tumor
Cyclin-Dependent Kinase 2 / metabolism
Humans
Male
Mice
Mice, Inbred NOD
Mitochondria / drug effects*
Neoplasms / drug therapy
Oxadiazoles / chemical synthesis,  chemistry*
Tumor Suppressor Protein p53 / metabolism
Xenograft Model Antitumor Assays
bcl-2-Associated X Protein / metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Oxadiazoles; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; 12794-10-4/Benzodiazepines; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 3.4.22.-/Caspases

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