Abstract |
A library of 3,5-disubstituted-1,2,4-oxadiazoles 7-9 and their bioisosters, 1,3,4-oxadiazole 14 and 1,3,4-thiadiazole 16, were synthesized and evaluated in vitro for their anticancer potential against a panel of six human cancer cell lines. The key step in the synthesis of oxadiazoles 7-9 involve coupling of amidoxime 6 with an appropriate carboxylic acid followed by thermal cyclization. The bioisosteres, 1,3,4-oxadiazole 14 and 1,3,4-thiadiazole 16 were prepared from the reaction of a common precursor diacylhydrazine 13 with thionyl chloride and Lawesson's reagent, respectively. The anticancer studies on the synthesized compounds revealed that presence of a cyclopentyloxy or n-butyloxy on the C-3 aryl ring and piperdin-4-yl or trichloromethyl at the C-5 position of 1,2,4-oxadiazole is essential for good activity. In particular, 1,2,4-oxadiazole 7i and analogue 1,3,4-thiadiazole 16 exhibited significant activity against DU145 (IC(50): 9.3 μM) and MDA-MB-231 (IC(50): 9.2 μM) cell lines, respectively.
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Authors | Dalip Kumar, Gautam Patel, Angela K Chavers, Kuei-Hua Chang, Kavita Shah |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 46
Issue 7
Pg. 3085-92
(Jul 2011)
ISSN: 1768-3254 [Electronic] France |
PMID | 21481985
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Carboxylic Acids
- Hydrazines
- Oxadiazoles
- Oximes
- Small Molecule Libraries
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Topics |
- Antineoplastic Agents
(chemical synthesis, pharmacology)
- Carboxylic Acids
(chemistry)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Cyclization
- Drug Screening Assays, Antitumor
- Humans
- Hydrazines
(chemistry)
- Inhibitory Concentration 50
- Oxadiazoles
(chemical synthesis, pharmacology)
- Oximes
(chemistry)
- Small Molecule Libraries
(chemical synthesis, pharmacology)
- Stereoisomerism
- Structure-Activity Relationship
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