- Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives
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This work deals with the design and synthesis of 18 barbituric acid derivatives bearing 1,3-dimethylbarbituric acid and cinnamic acid scaffolds to find potent anticancer agents. The target molecules were obtained through Knoevenagel condensation and acylation reaction. The cytotoxicity was assessed by the MTT assay. Flowcytometry was performed to determine the cell cycle arrest, apoptosis, ROS levels and the loss of MMP. The ratios of GSH/GSSG and the MDA levels were determined by using UV spectrophotometry. The results revealed that introducing substitutions (CF3, OCF3, F) on the meta- of the benzyl ring of barbituric acid derivatives led to a considerable increase in the antiproliferative activities compared with that of corresponding ortho- and para-substituted barbituric acid derivatives. Mechanism investigation implied that the 1c could increase the ROS and MDA level, decrease the ratio of GSH/GSSG and MMP, and lead to cell cycle arrest. Further research is needed for structural optimization to enhance hydrophilicity, thereby improve the biological activity of these compounds.
- Liu, Yue,Li, Peng-Xiao,Mu, Wen-Wen,Sun, Ya-Lei,Liu, Ren-Min,Yang, Jie,Liu, Guo-Yun
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- Synthesis, antiproliferative activity, and mechanism of action of a series of 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides
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Several new 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides 12a-s and 17t-v were synthesized by stirring in pyridine the (E)-3-(2-R1-3-R2-4-R3-phenyl) acrylic acid chlorides 11c-k and 11t-v with the appropriate anthranilamide derivatives 10a-c or the 5-iodoanthranilic acid 13. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell line panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). COMPARE analysis, effects on tubulin polymerization in cells and with purified tubulin, and effects on cell cycle distribution for 17t, the most active of the series, indicate that these new antiproliferative compounds act as antitubulin agents.
- Raffa, Demetrio,Maggio, Benedetta,Plescia, Fabiana,Cascioferro, Stella,Plescia, Salvatore,Raimondi, Maria Valeria,Daidone, Giuseppe,Tolomeo, Manlio,Grimaudo, Stefania,Di Cristina, Antonietta,Pipitone, Rosaria Maria,Bai, Ruoli,Hamel, Ernest
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supporting information; experimental part
p. 2786 - 2796
(2011/07/08)
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- Benzo[b]pyrano[3,2-h]acridin-7-one cinnamate compounds
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A compound selected from those of formula (I): wherein: X and Y represent a group selected from hydrogen, halogen, alkoxy, nitro, cyano, alkyl, alkenyl, polyhaloalkyl and —NRaRb wherein Ra and Rb are as defined
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Page/Page column 8
(2008/06/13)
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- PHARMACEUTICALLY ACTIVE BENZOXAZOLE, BENZTHIAZOLE AND BENZIMIDAZOLE ACID DERIVATIVES
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Compounds of formula (I): wherein R1, R2 and R3 are independently, hydrogen, halogen, CF3, OR6, NR7R8, NR8COR10, NR8SO2R10 or C1-6 alkyl optionally substituted by hydroxy, C1-6 alkoxy or NR7R8; R4 is NR8CONR8R9, NR8COR9, NR8SO2R9, or W-CONR8R9, where W is a bond, C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene; and R5 is Formula (A) methods for their synthesis, pharmaceutical compositions comprising them and their use in medicine, in particular for the treatment of cancer.
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Page 43; 44; 46
(2010/02/07)
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