trypanothione | 109658-48-2

• 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: trypanothione
• 英文别名: N¹,N⁸-bis(glutathionyl)spermidine；Bis(gamma-glutamyl-cysteinyl-glycinyl)spermidine；(2S)-2-amino-5-[[(2R)-1-[[2-[4-[3-[[2-[[(2R)-2-[[(4S)-4-amino-4-carboxybutanoyl]amino]-3-sulfanylpropanoyl]amino]acetyl]amino]propylamino]butylamino]-2-oxoethyl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid
• CAS: 109658-48-2
• 化学式: C₂₇H₄₉N₉O₁₀S₂
• 分子量: 723.872
• InChiKey: PHDOXVGRXXAYEB-VJANTYMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -9.1
• 重原子数：
  48
• 可旋转键数：
  27
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  315
• 氢给体数：
  13
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  trypanothione 在 Escherichia coli glyoxalase I 作用下， 生成
  参考文献：
  名称：

  Ni2+-activated glyoxalase I from Escherichia coli: Substrate specificity, kinetic isotope effects and evolution within the βαβββ superfamily

  摘要：

  The Escherichia coli glyoxalase system consists of the metalloenzymes glyoxalase I and glyoxalase II. Little is known regarding Ni2+-activated E. coli glyoxalase I substrate specificity, its thiol cofactor preference, the presence or absence of any substrate kinetic isotope effects on the enzyme mechanism, or whether glyoxalase I might catalyze additional reactions similar to those exhibited by related beta alpha beta beta beta structural superfamily members. The current investigation has shown that this two-enzyme system is capable of utilizing the thiol cofactors glutathionylspermidine and trypanothione, in addition to the known tripeptide glutathione, to convert substrate methylglyoxal to non-toxic D-lactate in the presence of Ni2+ ion. E. coli glyoxalase I, reconstituted with either Ni2+ or Cd2+, was observed to efficiently process deuterated and non-deuterated phenylglyoxal utilizing glutathione as cofactor. Interestingly, a substrate kinetic isotope effect for the Ni2+-substituted enzyme was not detected; however, the proton transfer step was observed to be partially rate limiting for the Cd2+-substituted enzyme. This is the first non-Zn2+-activated GlxI where a metal ion-dependent kinetic isotope effect using deuterium-labelled substrate has been observed. Attempts to detect a glutathione conjugation reaction with the antibiotic fosfomycin, similar to the reaction catalyzed by the related superfamily member FosA, were unsuccessful when utilizing the E. coli glyoxalase I E56A mutein. (c) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jinorgbio.2011.11.008
• 作为产物：
  描述：

  亚精胺 在 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 生成 trypanothione
  参考文献：
  名称：

  Solid phase applications of Dde and the analogue Nde: Synthesis of trypanothione disulphide

  摘要：

  Bis - Dde and Nde spermidine derivatives selectively protected on the primary amines were readily prepared and attached via the secondary amine group to a p-nitrophenyl-1-chloroformate pre-activated HMPA resin. Deprotection for Nde was monitored by colour change and UV absorption at 290 nm following which the trypanothione backbone was assembled by standard Fmoc procedures. Release from the resin with TFA and subsequent oxidation gave the trypanothione disulphide in > 80% overall yield. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(97)01010-1
• 作为试剂：
  描述：

  (S_CS_S)-L-methionine sulfoxide 在 乙二胺四乙酸 、 trypanoredoxin I 、 Trypanosoma cruzi N-terminally His-tagged methionine sulfoxide reductase type A 、 Trypanosoma cruzi trypanothione reductase 、 trypanothione 、 还原型辅酶II(NADPH)四钠盐 作用下， 生成 L-蛋氨酸
  参考文献：
  名称：

  Functional characterization of methionine sulfoxide reductase A from Trypanosoma spp.

  摘要：

  Methionine is an amino acid susceptible to being oxidized to methionine sulfoxide (MetSO). The reduction of MetSO to methionine is catalyzed by methionine sulfoxide reductase (MSR), an enzyme present in almost all organisms. In trypanosomatids, the study of antioxidant systems has been mainly focused on the involvement of trypanothione, a specific redox component in these organisms. However, no information is available concerning their mechanisms for repairing oxidized proteins, which would be relevant for the survival of these pathogens in the various stages of their life cycle. We report the molecular cloning of three genes encoding a putative A-type MSR in trypanosomatids. The genes were expressed in Escherichia coli, and the corresponding recombinant proteins were purified and functionally characterized. The enzymes were specific for L-Met(S)SO reduction, using Trypanosoma cruzi tryparedoxin I as the reducing substrate. Each enzyme migrated in electrophoresis with a particular profile reflecting the differences they exhibit in superficial charge. The in vivo presence of the enzymes was evidenced by immunological detection in replicative stages of T cruzi and Trypanosoma brucei. The results support the occurrence of a metabolic pathway in Trypanosoma Spp. involved in the critical function of repairing oxidized macromolecules. (C) 2010 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.freeradbiomed.2010.10.695

文献信息

• [EN] GOLD COMPOUNDS AND THEIR USE IN THERAPY<br/>[FR] COMPOSÉS D'OR ET LEUR UTILISATION DANS LE CADRE D'UNE THÉRAPIE
  申请人：AUSPHERIX LTD

  公开号：WO2018220171A1

  公开（公告）日：2018-12-06

  Compound of formula (I) and pharmaceutically acceptable salts and solvates thereof are described, wherein: Px selected from (P1), (P2) or (P3); The compounds are useful in the prevention or treatment of a bacterial infection.

  描述了化合物的公式（I）及其药用可接受的盐和溶剂化合物，其中：Px选自（P1）、（P2）或（P3）；这些化合物在预防或治疗细菌感染方面是有用的。
• COMPOUNDS USEFUL AGAINST KINETOPLASTIDEAE PARASITES
  申请人：Davioud-Charvet Elisabeth

  公开号：US20120214996A1

  公开（公告）日：2012-08-23

  Dibenzylidene and heterobenzylideneacetone derivatives, related 4-piperidones, related 4-thiopyranones and the corresponding sulfinyl- and sulfonyl-analogues for their use for prophylaxis or treatment of trypanosomiasis and leishmaniasis.

  二苄基亚烷和杂二苄基亚烷乙酮衍生物，相关的4-哌啶酮，相关的4-噻opyranones以及相应的亚磺酰基和磺酰基类似物，用于预防或治疗锥虫病和利什曼病。
• Benzofuranyl 3,5-bis-Polyamine derivatives as time-Dependent inhibitors of trypanothione reductase
  作者：Chris J. Hamilton、Ahilan Saravanamuthu、Alan H. Fairlamb、Ian M. Eggleston

  DOI：10.1016/s0968-0896(03)00344-4

  日期：2003.8

  inhibitors of the protozoan oxidoreductase trypanothione reductase are reported. These molecules were designed as simplified mimetics of the naturally occurring spermidine-bridged macrocyclic alkaloid lunarine 1, a known time-dependent inhibitor of trypanothione reductase. In this series of compounds the bis-polyaminoacrylamide derivatives 2-4 were all shown to be competitive inhibitors, but only the b

  报道了作为原生动物氧化还原酶锥虫硫酮还原酶的时间依赖性抑制剂的3，5-二取代苯并呋喃衍生物的合成和评价。这些分子被设计为天然存在的亚精胺桥联的大环生物碱lunarine 1的简化模拟物，后者是一种已知的时间依赖性的锥虫硫醚还原酶抑制剂。在这一系列化合物中，双-聚氨基丙烯酰胺衍生物2-4均被证明是竞争性抑制剂，但只有双4-甲基-哌嗪-1-基-丙基丙烯酰胺衍生物4表现出时间依赖性。已经确定了1和4的时间依赖性锥虫硫醚还原酶失活的动力学，并在本文中进行了比较和讨论。
• BISNAPHTHALIMIDOPROPYL DERIVATIVE COMPOUNDS WITH ANTI-PARASITE AND ANTI-CANCER ACTIVITY
  申请人：Cordeiro Da Silva Anabela

  公开号：US20090062329A1

  公开（公告）日：2009-03-05

  The bisnaphthalimidopropyl derivatives with anti-parasitic and anti-cancer activity. Bisnaphthalimidopropyl derivatives (A) BNIPPut, BNIPDapen, BNIPDhex, BNIPDahep, BNIPDaoct, BNIPDanon, BNTPDadec, BNIPDadod, BNPDpta, BNIPDeta were synthesized in yields ranging from 50-70 and their cytotoxicity against colon cancer cells (CaCo-2) and the parasite Leishmania infantum determined using the MTT assay and by luciferase activity present in parasite, respectively. Cytotoxicity within CaCo-2 cells was manifested with IC 50 values between 0.3 and 22 m M after 48 h of compounds incubation. Against Leishmania infantum , IC 50 values were encompassed within a narrower concentration range of 0.39-2.09 m M, for pro-mastigote form, and between 5.24 and 17.42 m M, for axenic amastigote and between 2.43 and 9.52 m M, for intracellular amastigote forms. These compounds can be an alternative to the normal therapeutic in the fields below (A), could be a solution to the toxicity and resistance related to the compounds existent in the market. Point of diversity.

  这些双萘酰亚胺丙基衍生物具有抗寄生虫和抗癌活性。双萘酰亚胺丙基衍生物（A）BNIPPut、BNIPDapen、BNIPDhex、BNIPDahep、BNIPDaoct、BNIPDanon、BNTPDadec、BNIPDadod、BNPDpta、BNIPDeta的合成产率在50-70之间，并通过MTT测定和寄生虫Leishmania infantum中的荧光素酶活性评估它们对结肠癌细胞（CaCo-2）的细胞毒性。在48小时化合物孵育后，CaCo-2细胞内的细胞毒性表现为IC50值在0.3和22 m M之间。对于Leishmania infantum，IC50值在0.39-2.09 m M的较窄浓度范围内，适用于原鞭毛体形式，以及在5.24和17.42 m M之间，适用于离体无菌性无鞭毛体和在2.43和9.52 m M之间，适用于细胞内无鞭毛体形式。这些化合物可能是以下领域中常规治疗的替代品（A），可能是解决市场上现有化合物相关毒性和耐药性的解决方案。多样性的观点。
• N5-substituted benzo¬2,3|azepino¬4,5-b|indol-6-ones for treating tropical diseases
  申请人：Molisa GmbH

  公开号：EP1757607A1

  公开（公告）日：2007-02-28

  The present invention relates to novel N5-substituted-benzo[2,3]azepino[4,5-b]indol-6-ones of the general formula (1): and pharmaceutically acceptable salts thereof, the use of these compounds as pharmaceutically active agents, especially for the prophylaxis and/or treatment of South American trypanosomiasis, African trypanosomiasis, sleeping sickness, Kala-Azar, visceral leishmaniasis, Baghdad boil or Aleppo boil, cutaneous leishmaniasis (CL), espundia, Chagas disease, mucocutaneous leishmaniasis (MCL), trichomoniasis, urogenital trichomonosis, giardiasis, lamblia dysentery, amoebiasis, primary amebic meningoencephalitis (PAM), keratitis or meningitis, coccidiosis, sarcosporidosis, toxoplasmosis, Malaria tropica, Malaria tertiana, Malaria quartana, pneumocystis carinii, pneumonia, pneumocystosis, Balantidium dysentery, and oriental sore. Furthermore, the present invention is directed towards pharmaceutical compositions containing at least one of the N5-substituted-benzo[2,3]azepino[4,5-b]indol-6-ones and/or pharmaceutically acceptable salts thereof.

  本发明涉及一种新型的N5-取代苯并[2,3]哌啶[4,5-b]吲哚-6-酮，其通式为(1)，以及其药学上可接受的盐，这些化合物作为药物活性剂的用途，特别用于南美锥虫病、非洲锥虫病、睡眠病、卡拉阿扎尔病、内脏利什曼病、巴格达疖或阿勒颇疖、皮肤利什曼病（CL）、恩普迪亚、查加斯病、粘膜皮肤利什曼病（MCL）、滴虫病、泌尿生殖道滴虫病、贾第虫病、贾第虫病性痢疾、阿米巴病、原发性阿米巴脑膜脑炎（PAM）、角膜炎或脑膜炎、球虫病、肉囊虫病、弓形虫病、疟疾疟疾、三日疟、四日疟、肺孢子虫肺炎、肺孢子虫病、巴兰蒂迪痢疾和东方疮的预防和/或治疗。此外，本发明还涉及含有至少一种N5-取代苯并[2,3]哌啶[4,5-b]吲哚-6-酮和/或其药学上可接受的盐的药物组合物。