title: 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.
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani, Rajasthan 333 031, India. dalipk@bits-pilani.ac.in
authors.forename: Dalip
authors.initials: D
authors.lastname: Kumar
authors.forename: Gautam
authors.initials: G
authors.lastname: Patel
authors.forename: Angela K
authors.initials: AK
authors.lastname: Chavers
authors.forename: Kuei-Hua
authors.initials: KH
authors.lastname: Chang
authors.forename: Kavita
authors.initials: K
authors.lastname: Shah
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002264:Carboxylic Acids / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003500:Cyclization; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D020128:Inhibitory Concentration 50; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D010091:Oximes / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D006834:Hydrazines; D010069:Oxadiazoles; D010091:Oximes; D054852:Small Molecule Libraries