- Synthesis and antiproliferative activity of RITA and its analogs
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The synthesis of RITA and a variety of five-membered heterocyclic triads by the cyclocondensation of 1,4-bis(5-substituted-2-thienyl or 2-furyl)-1,3-butadiynes with water or Na2S·9H2O in the presence of KOH in DMSO is described. The study on the antiproliferative activities against K562, MCF-7, A549, and HCT116 tumor cells has revealed that some of the heterocyclic triads show higher antiproliferative activities than RITA, depending on the structures of substituents, the property of heteroatoms as well as their numbers.
- Jiang, Jianhua,Ding, Chao,Li, Lulu,Gao, Chunmei,Jiang, Yuyang,Tan, Chunyan,Hua, Ruimao
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p. 6635 - 6638
(2015/01/16)
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- Efficient synthesis of RITA and its analogues: Derivation of analogues with improved antiproliferative activity via modulation of p53/miR-34a pathway
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A novel approach to synthesize RITA by practical palladium-catalyzed C-C bond-forming Suzuki reactions at room temperature was developed, which was used for deriving a series of substituted tricyclic α-heteroaryl (furan/thiophene) analogues of RITA under mild conditions. These novel analogues showed notable antiproliferative activity against cancer cell lines with wild-type p53 (i.e., HCT116, A549, MCF-7 and K562), but much less activity in HCT116/p53-/- cells. In particular, compound 1f demonstrated promising antiproliferative activity compared to RITA, with IC50 = 28 nM in MCF-7 vs. 54 nM for RITA, and cancer cell selectivity. Compound 1f markedly activated p53 in HCT116 cells at 100 nM, triggering apoptosis. Importantly, we found that both RITA and compound 1f induced G 0/G1 cell cycle arrest by up-regulating miR-34a, which in turn down-regulated the expression of cell cycle-related proteins CDK4 and E2F1. In summary, this study reports an effective synthetic approach for RITA and its analogues, and elucidates a novel antiproliferative mechanism of these compounds. The Royal Society of Chemistry 2012.
- Lin, Jinshun,Jin, Xiuli,Bu, Yiwen,Cao, Deliang,Zhang, Nannan,Li, Shangfu,Sun, Qinsheng,Tan, Chunyan,Gao, Chunmei,Jiang, Yuyang
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p. 9734 - 9746
(2013/01/16)
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