γ-(6-aminohexyl)folic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: γ-(6-aminohexyl)folic acid
• 英文别名: 5-(6-aminohexylamino)-2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methylamino]benzoyl]amino]-5-oxopentanoic acid
• 化学式: C₂₅H₃₃N₉O₅
• 分子量: 539.594
• InChiKey: DAWBZYKLNGOKLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  39
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  227
• 氢给体数：
  7
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5,10,15-tri(p-tolyl)-20-(p-carboxyphenyl)porphyrin succinimid-1-yl ester 、 γ-(6-aminohexyl)folic acid 在 吡啶 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 以34%的产率得到
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of folic acid targeted tetraphenylporphyrin as novel photosensitizers for selective photodynamic therapy

  摘要：

  Photodynamic therapy (PDT) is a cancer treatment involving systemic administration of a tumor-localizing photosensitizer; this, when activated by the appropriate light wavelength, interacts with molecular oxygen to form a toxic, short-lived species known as singlet oxygen, which is thought to mediate cellular death. Targeted PDT offers the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues.Two new conjugates of three components, folic acid/hexane-1,6-diamine/4-carboxyphenylporphyrine 1 and folic acid/2,2'-(ethylenedioxy)-bis-ethylamine/4-carboxyphenylporphyrine 2 were synthesized. The conjugates were characterized by H-1 NMR, MALDI, UV-visible spectroscopy, and fluorescence quantum yield. The targeted delivery of these photoactive compounds to KB nasopharyngeal cell line, which is one of the numerous tumor cell types that overexpress folate receptors was studied. It was found that after 24 h incubation, conjugates I and 2 cellular uptake was on average 7-fold higher than tetraphenylporphyrin (TPP) used as reference and that 1 and 2 cellular uptake kinetics increased steadily over the 24 h period, suggesting an active transport via receptor-mediated endocytosis. In corresponding results, conjugates I and 2 accumulation displayed a reduction of 70% in the presence of a competitive concentration of folic acid. Survival measurements demonstrated that KB cells were significantly more sensitive to conjugated porphyrins-mediated PDT. Under the same experimental conditions and the same photosensitizer concentration, TPP displayed no photocytotoxicity while conjugates 1 and 2 showed photodynamic activity with light dose values yielding 50% growth inhibition of 22.6 and 6.7 J/cm(2), respectively. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.02.025
• 作为产物：
  描述：

  N-Boc-1,6-己二胺 在 吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二甲基亚砜 为溶剂， 反应 20.0h， 生成 γ-(6-aminohexyl)folic acid
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of folic acid targeted tetraphenylporphyrin as novel photosensitizers for selective photodynamic therapy

  摘要：

  Photodynamic therapy (PDT) is a cancer treatment involving systemic administration of a tumor-localizing photosensitizer; this, when activated by the appropriate light wavelength, interacts with molecular oxygen to form a toxic, short-lived species known as singlet oxygen, which is thought to mediate cellular death. Targeted PDT offers the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues.Two new conjugates of three components, folic acid/hexane-1,6-diamine/4-carboxyphenylporphyrine 1 and folic acid/2,2'-(ethylenedioxy)-bis-ethylamine/4-carboxyphenylporphyrine 2 were synthesized. The conjugates were characterized by H-1 NMR, MALDI, UV-visible spectroscopy, and fluorescence quantum yield. The targeted delivery of these photoactive compounds to KB nasopharyngeal cell line, which is one of the numerous tumor cell types that overexpress folate receptors was studied. It was found that after 24 h incubation, conjugates I and 2 cellular uptake was on average 7-fold higher than tetraphenylporphyrin (TPP) used as reference and that 1 and 2 cellular uptake kinetics increased steadily over the 24 h period, suggesting an active transport via receptor-mediated endocytosis. In corresponding results, conjugates I and 2 accumulation displayed a reduction of 70% in the presence of a competitive concentration of folic acid. Survival measurements demonstrated that KB cells were significantly more sensitive to conjugated porphyrins-mediated PDT. Under the same experimental conditions and the same photosensitizer concentration, TPP displayed no photocytotoxicity while conjugates 1 and 2 showed photodynamic activity with light dose values yielding 50% growth inhibition of 22.6 and 6.7 J/cm(2), respectively. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.02.025

文献信息

• [EN] CONJUGATE HAVING TUMOR SELECTIVITY FOR TARGETED TREATMENT<br/>[FR] CONJUGUÉ PRÉSENTANT UNE SÉLECTIVITÉ VIS-À-VIS DES TUMEURS QUI PEUT ÊTRE UTILISÉ POUR UN TRAITEMENT CIBLÉ
  申请人：DONGSUNG PHARM CO LTD

  公开号：WO2013051778A1

  公开（公告）日：2013-04-11

  본 발명은 표적 치료에 관한 종양에 선택성이 있는 콘쥬게이트(conjugate)에 관한 것으로, 보다 상세하게는 광 및 음향 과민제, 혈관형성 억제제 및 타이로신 카이나제 억제제의 성질을 결합한 것을 특징으로 하는 표적 치료에 관한 종양에 선택성이 있는 콘쥬게이트에 관한 것이다. 상기 콘쥬게이트는 광 및 음향 과민제, 혈관형성 억제제 및 타이로신 카이나제 억제제, 표적 리간드 및 링커를 포함하는 것을 특징으로 할 수 있다. 본 발명인표적 치료에 관한 종양에 선택성이 있는 콘쥬게이트 및 이의 응용은 광역학치료제에 보다 특이적으로 그리고 약리학적으로 관련이 있는 본 발명은 혈관형성과 타이로신 카이나제 억제제의 성질을 가지며, 암 및 다른 질환 치료를 위한 의약품을 제조에 사용될 수 있다. 특히 본 발명은 curcuminoids와 포르피린 conjugates에 기초한 약물, 암과 다른 질환 상태 치료를 위한 curcuminoids와 porphyrins conjugate에 기초한 화합물을 기반으로 한 화합물 제법과 관련이 있다. 발명은 또한 이 조성물에 기초한 치료법과 관련이 있고, 그것이 제안된 약물의 항암, 항혈관형성, 억제 효과를 제공할 수 있고, 수용액에서 우수한 용해성, 생체 이용률, 안정성, 암과 다른 질환 치료에서 독성의 결여라는 유리한 효과를 갖고 있다. 나아가 본 발명은 암 및 기타 질병 상태의 치료를 위한 구강, 비강 및 직장 투여용으로 사용될 수 있다.
• Design, synthesis, and biological evaluation of folic acid targeted tetraphenylporphyrin as novel photosensitizers for selective photodynamic therapy
  作者：Raphaël Schneider、Frédéric Schmitt、Céline Frochot、Yves Fort、Natacha Lourette、François Guillemin、Jean-François Müller、Muriel Barberi-Heyob

  DOI：10.1016/j.bmc.2005.02.025

  日期：2005.4

  Photodynamic therapy (PDT) is a cancer treatment involving systemic administration of a tumor-localizing photosensitizer; this, when activated by the appropriate light wavelength, interacts with molecular oxygen to form a toxic, short-lived species known as singlet oxygen, which is thought to mediate cellular death. Targeted PDT offers the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues.Two new conjugates of three components, folic acid/hexane-1,6-diamine/4-carboxyphenylporphyrine 1 and folic acid/2,2'-(ethylenedioxy)-bis-ethylamine/4-carboxyphenylporphyrine 2 were synthesized. The conjugates were characterized by H-1 NMR, MALDI, UV-visible spectroscopy, and fluorescence quantum yield. The targeted delivery of these photoactive compounds to KB nasopharyngeal cell line, which is one of the numerous tumor cell types that overexpress folate receptors was studied. It was found that after 24 h incubation, conjugates I and 2 cellular uptake was on average 7-fold higher than tetraphenylporphyrin (TPP) used as reference and that 1 and 2 cellular uptake kinetics increased steadily over the 24 h period, suggesting an active transport via receptor-mediated endocytosis. In corresponding results, conjugates I and 2 accumulation displayed a reduction of 70% in the presence of a competitive concentration of folic acid. Survival measurements demonstrated that KB cells were significantly more sensitive to conjugated porphyrins-mediated PDT. Under the same experimental conditions and the same photosensitizer concentration, TPP displayed no photocytotoxicity while conjugates 1 and 2 showed photodynamic activity with light dose values yielding 50% growth inhibition of 22.6 and 6.7 J/cm(2), respectively. (c) 2005 Elsevier Ltd. All rights reserved.