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Synthesis of novel 1,2,4-oxadiazoles and analogues as potential anticancer agents.

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.
AuthorsDalip Kumar, Gautam Patel, Angela K Chavers, Kuei-Hua Chang, Kavita Shah
JournalEuropean journal of medicinal chemistry (Eur J Med Chem) Vol. 46 Issue 7 Pg. 3085-92 (Jul 2011) ISSN: 1768-3254 [Electronic] France
PMID21481985 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Masson SAS. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Carboxylic Acids
  • Hydrazines
  • Oxadiazoles
  • Oximes
  • Small Molecule Libraries
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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