Synthesis and anticancer activities of novel 3,5-disubstituted-1,2,4-oxadiazoles

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 10, 2009, Pages 2739-2741

  Kumar, Dalip ^a   Patel, Gautam ^a   Johnson, Emmanuel O ^b   Shah, Kavita ^b  

^a BIRLA INSTITUTE OF TECHNOLOGY AND SCIENCE   (India)

^b PURDUE UNIVERSITY   (United States)

Author keywords

1,2,4 Oxadiazole; Anticancer agent; Selective cytotoxicity

Indexed keywords

1,2,4 OXADIAZOLE DERIVATIVE; CARBOXYLIC ACID DERIVATIVE; OXIME DERIVATIVE;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; DRUG CYTOTOXICITY; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SPECIFICITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IN VITRO STUDY; REACTION ANALYSIS; STRUCTURE ACTIVITY RELATION;

ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; OXADIAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 65449146373     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.03.158     Document Type: Article

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12. Synthesis of amidoxime 2: To a mixture of appropriate benzonitrile (10 mmol) and hydroxyl-amine hydrochloride (20 mmol) in 50 mL of ethanol was added dropwise aqueous solution of sodium hydroxide (20 mmol, 10 mL) while maintaining temperature at 0 °C. The resulting mixture was allowed to reflux with stiring for 18 h. Ethanol was distilled off under reduced pressure and the crude product was taken into 50 mL of water. The pH (∼2) of the solution was adjusted with 1N HCl and the aqueous phase was washed with ethylacetate (2 × 25 mL). Upon cooling (0 °C) and neutralization with sodium carbonate gave off white precipitate which was filtered, washed and air dried at 60 °C to afford pure amidoxime 2.
13. Synthesis of 3,5-disubstituted-1,2,4-oxadiazole 3: A solution of appropriate carboxylic acid (0.8 mmol) in dry DMF (1 mL) was cooled to 0 °C and added dicyclohexylcarbodiimide (1.2 mmol) under nitrogen atmosphere and stirred the reaction mixture at the same temperature for 1 h. To this reaction mixture appropriate benzamidoxime 2 (0.8 mmol) was added and stirred at 0 °C for 0.5 h. The reaction mixture was slowly brought to 30 °C, and stirring continued for another 3 h. Gradually temperature was raised to 110 °C, and further stirred for 10 h. The reaction mixture was cooled to 25 °C and poured into ice-cold water (25 mL). Upon addition of ethylacetate (25 mL) and stirring for 10 min, crystals of dicyclohexylurea separated out and removed by filtration. Separated aqueous phase was extracted with ethylacetate (2 × 20 mL) and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate. Ethylacetate was distilled off and the residue thus obtained was purified by flash column chromatography using ethylacetate-hexane (0-25%) as eluent to afford pure oxadiazole 3.
14. 3, 200 MHz)
15. 3 cells per well for 12 h. Cells were incubated with various concentrations of the compounds ranging from 10 nM-1 mM. After 24 h, MTT (3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazoliumbromide) was added to the final concentration of 0.5 mg/ml and incubated for 30 min. The cells were washed twice with PBS and lysed in dimethylsulfoxide, and the absorbance was measured at 570 nm.