1-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)propan-2-yl 2-methoxy-2-(naphthalen-1-yl)acetate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 1-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)propan-2-yl 2-methoxy-2-(naphthalen-1-yl)acetate
• 英文别名: 1-(1,3-Dimethyl-2,6-dioxopurin-7-yl)propan-2-yl 2-methoxy-2-naphthalen-1-ylacetate；1-(1,3-dimethyl-2,6-dioxopurin-7-yl)propan-2-yl 2-methoxy-2-naphthalen-1-ylacetate
• 化学式: C₂₃H₂₄N₄O₅
• 分子量: 436.467
• InChiKey: ARAUAPYQZOJCJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  94
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-萘乙醇酸 在 4-二甲氨基吡啶 、 calcium sulfate 、 氯化亚砜 、 lithium hydroxide monohydrate 、 三乙胺 、 silver(l) oxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 苯 为溶剂， 反应 83.0h， 生成 1-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)propan-2-yl 2-methoxy-2-(naphthalen-1-yl)acetate
  参考文献：
  名称：

  Synthesis of novel proxyphylline derivatives with dual Anti-Candida albicans and anticancer activity

  摘要：

  Three out of 16 newly synthesized 1,3-dimethylxanthine derivatives (proxyphylline analogues) exhibited consistencies between antifungal and anticancer properties. Proxyphylline possessing 1-(10H-phenothiazin-10-yl)propan-2-yl (6) and polybrominated benzimidazole (41) or benzotriazole moiety (42) remained selectively cidal against Candida albicans (lg R >= 3 at conc. of 31, 36 and 20 mu M, respectively) however not against normal mammalian Vero cell line in vitro (IC50 >= 280 mu M) and Galleria mellonella in vivo. These compounds also displayed moderate antineoplastic activity against human breast adenocarcinoma (MCF-7) cell line (EC50 = 80 mu M) and high against peripheral blood T lymphoblast (CCRF-CEM) (EC50 = 6.3-6.5 mu M). In addition, 6 and 42 exerted: (1) dual activity against fungal adhesion and damage mature biofilm; (2) necrosis of planktonic cells due to loss of membrane function and of structural integrity; (3) biochemical (inhibition of sessile cell respiration) and morphological changes in cell wall polysaccharide contents. Therefore, leading proxyphylline derivatives can be employed to prevent cancer-associated biofilm Candida infections. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.02.077

文献信息

• Synthesis of novel proxyphylline derivatives with dual Anti-Candida albicans and anticancer activity
  作者：Paweł Borowiecki、Patrycja Wińska、Maria Bretner、Małgorzata Gizińska、Mirosława Koronkiewicz、Monika Staniszewska

  DOI：10.1016/j.ejmech.2018.02.077

  日期：2018.4

  Three out of 16 newly synthesized 1,3-dimethylxanthine derivatives (proxyphylline analogues) exhibited consistencies between antifungal and anticancer properties. Proxyphylline possessing 1-(10H-phenothiazin-10-yl)propan-2-yl (6) and polybrominated benzimidazole (41) or benzotriazole moiety (42) remained selectively cidal against Candida albicans (lg R >= 3 at conc. of 31, 36 and 20 mu M, respectively) however not against normal mammalian Vero cell line in vitro (IC50 >= 280 mu M) and Galleria mellonella in vivo. These compounds also displayed moderate antineoplastic activity against human breast adenocarcinoma (MCF-7) cell line (EC50 = 80 mu M) and high against peripheral blood T lymphoblast (CCRF-CEM) (EC50 = 6.3-6.5 mu M). In addition, 6 and 42 exerted: (1) dual activity against fungal adhesion and damage mature biofilm; (2) necrosis of planktonic cells due to loss of membrane function and of structural integrity; (3) biochemical (inhibition of sessile cell respiration) and morphological changes in cell wall polysaccharide contents. Therefore, leading proxyphylline derivatives can be employed to prevent cancer-associated biofilm Candida infections. (C) 2018 Elsevier Masson SAS. All rights reserved.