1-(3-nitrophenyl)-9H-pyrido[3,4-b]indole-3-carbohydrazide | 1085709-08-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 1-(3-nitrophenyl)-9H-pyrido[3,4-b]indole-3-carbohydrazide
• CAS: 1085709-08-5
• 化学式: C₁₈H₁₃N₅O₃
• 分子量: 347.333
• InChiKey: UUHJMJYFDBJNDK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(3-nitrophenyl)-9H-pyrido[3,4-b]indole-3-carbohydrazide 在 盐酸 、 sodium nitrite 作用下， 以 水 为溶剂， 生成
  参考文献：
  名称：

  Development of novel β-carboline-based hydroxamate derivatives as HDAC inhibitors with antiproliferative and antimetastatic activities in human cancer cells

  摘要：

  A series of novel beta-carboline-based hydroxamate derivatives 12a-k were designed and synthesized, and their biological activities in a series of in vitro assays were evaluated. Several of these beta-carboline derivatives not only showed excellent HDAC1/3/6 inhibitory effects, but also displayed significant antitumor activities against five human cancer cells. The most potent compound 12f demonstrated the highest anticancer potency against cancer cell lines with IC50 values of 0.53-1.56 mu M, which was considerably more potent than harmine (IC50 = 46.7-55.3 mu M) and also three-to ten-fold lower than that of SAHA (IC50=4.48-6.26 mu M). Immunoblot analysis revealed that 12f dose-dependently inhibited histone H3 and a-tubulin acetylation, confirming its HDAC inhibitory effects. Moreover, 12f significantly arrested HepG2 cells at G2/M phase through inhibiting cell cycle related protein CDK1 and cyclin B in a concentration dependent manner. Interestingly, 12f also exerted strong anti-metastasis activity by simultaneously reducing the protein level of MMP2 and MMP9 and inhibiting MAPK signaling pathway. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.12.061
• 作为产物：
  描述：

  L-色氨酸 在 硫酸 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 48.0h， 生成 1-(3-nitrophenyl)-9H-pyrido[3,4-b]indole-3-carbohydrazide
  参考文献：
  名称：

  β-咔啉3-（取代-咔唑）衍生物的合成及抗肿瘤活性

  摘要：

  合成了一系列在C-3处带有取代的碳酰肼部分的β-咔啉衍生物，并评估了其对八种人类癌细胞系的抗肿瘤活性。通常，β-咔啉N-（取代的亚苄基）碳酰肼显示出比其N-（亚烷基）碳酰肼类似物更大的抗肿瘤活性。β-咔啉N-（取代的亚苄基）碳酰肼的N 9甲基化导致抗肿瘤活性降低。在所测试的化合物中，苄基碳酰肼3，4，11，13，16，21和22是最活跃的，具有IC对于八种肿瘤细胞系中的六种，有50种小于10μM。衍生物4对所有测试的细胞系表现出最显着的活性，对肾脏（786-0）细胞系具有显着的细胞毒性（IC 50  = 0.04μM）。在Ehrlich实体癌测定中测定化合物4的体内抗肿瘤活性。

  DOI：

  10.1016/j.bmc.2011.08.059

文献信息

• Design, Synthesis and Bioactivity Evaluation of Novel β-carboline 1,3,4-oxadiazole Derivatives
  作者：Zhi-Jun Zhang、Jing-Jing Zhang、Zhi-Yan Jiang、Guo-Hua Zhong

  DOI：10.3390/molecules22111811

  日期：——

  A series of novel β-carboline 1,3,4-oxadiazole derivatives were designed and synthesized, and the in vitro cytotoxic activity against Sf9 cells and growth inhibitory activity against Spodoptera litura were evaluated. Bioassay results showed that most of these compounds exhibited excellent in vitro cytotoxic activity. Especially, compound 37 displayed the best efficacy in vitro (IC50 = 3.93 μM), and

  设计并合成了一系列新型β-咔啉1,3,4-恶二唑衍生物，并评估了其体外对Sf9细胞的细胞毒活性和对斜纹夜蛾的生长抑制活性。生物测定结果表明，这些化合物中的大多数表现出优异的体外细胞毒活性。特别是，化合物 37 在体外表现出最佳功效（IC50 = 3.93 μM），并且比喜树碱（CPT）（IC50 = 18.95 μM）强五倍。此外，化合物 5 和 37 可以诱导细胞凋亡和细胞周期停滞并刺激 Sf9 细胞中的 Sf-caspase-1 活化。体内生物测定还表明，化合物5和37可以显着抑制斜纹夜蛾幼虫的生长，降低幼虫和蛹的重量。根据这些生物测定结果，
• Synthesis and antiviral activity of β-carboline derivatives bearing a substituted carbohydrazide at C-3 against poliovirus and herpes simplex virus (HSV-1)
  作者：Anelise S. Nazari Formagio、Patricia R. Santos、Karine Zanoli、Tania Ueda-Nakamura、Lilian T. Düsman Tonin、Celso V. Nakamura、Maria Helena Sarragiotto

  DOI：10.1016/j.ejmech.2009.07.005

  日期：2009.11

  Several novel 1,3-disubstituted β-carboline derivatives bearing a substituted carbohydrazide group at C-3 were synthesized and evaluated for their antiviral activity against vaccinal poliovirus (VP) and herpes simplex virus type 1 (HSV-1). The cytotoxicity and selectivity index of the active compounds were also evaluated. Among the synthesized derivatives, compounds 10 and 11 displayed potent activity

  合成了几种新颖的在C-3带有一个取代的碳酰肼基团的1,3-二取代的β-咔啉衍生物，并评估了它们对疫苗脊髓灰质炎病毒（VP）和1型单纯疱疹病毒（HSV-1）的抗病毒活性。还评估了活性化合物的细胞毒性和选择性指数。在合成的衍生物中，化合物10和11对疫苗的脊髓灰质炎病毒和HSV-1病毒均显示出有效的活性。化合物10表现出对HSV-1病毒的最高选择性指数（SI = 2446.8）和低细胞毒性（CC 50  = 1150.0±67.3μM）。病毒产量抑制试验表明化合物10能够在病毒吸附之前和期间抑制HSV-1斑块的形成。在化合物处理过的细胞中观察到的特征性小噬斑图案表明，化合物10抑制了病毒向邻近细胞的传播。通过使用Lipinski规则确定亲脂性，拓扑极性表面积（TPSA），吸收率（％ABS）和简单分子描述符，对预测新型合成β-咔啉衍生物的ADME性质进行了计算研究。
• Synthesis and evaluation of novel hybrids β -carboline-4-thiazolidinones as potential antitumor and antiviral agents
  作者：Valéria Aquilino Barbosa、Paula Baréa、Renata Sespede Mazia、Tania Ueda-Nakamura、Willian Ferreira da Costa、Mary Ann Foglio、Ana Lucia T. Goes Ruiz、João Ernesto de Carvalho、Débora Barbosa Vendramini–Costa、Celso Vataru Nakamura、Maria Helena Sarragiotto

  DOI：10.1016/j.ejmech.2016.10.018

  日期：2016.11

  -carboxamide series (18–23) showed a potent activity and high selectivity for glioma (U251) and ovarian (OVCAR-3) cancer cell lines. Also, some β-carboline-4-thiazolidinone hybrids showed potent antiviral activity against Herpes simplex virus type-1. The N-(2-substituted-aryl-4-thiazolidinone)-carboxamide moiety in 18, 19 and 22 confer a potent anti-HSV-1 activity for these derivatives, which presented

  合成了一系列新颖的杂种β-咔啉-4-噻唑烷酮，并评估了其对人癌细胞的体外抗肿瘤活性以及对单纯疱疹病毒1型（HSV-1）的抗病毒活性。从N' - （咪唑烷-2-亚基-4-噻唑烷酮） - β咔啉-3-碳酰肼系列（9-11），Ç ompounds 9C和11d中是最活跃的，表现出生长抑制50％（GI 50）的值小于对于所有测试的细胞系，均大于5μM 化合物9c中，轴承4 -二甲氨基苯基在C-1 β选择-咔啉来进行有关细胞死亡和细胞周期图的进一步研究，重点是人肾腺癌细胞系786-0。用25μM的化合物9c处理在处理15小时后会诱导细胞死亡，其特征在于磷脂酰丝氨酸的暴露和膜完整性的丧失。此外，用12.5μM的处理可促进亚G1阻滞，这表明细胞死亡。N-（2-取代-芳基-4-噻唑烷酮）-β-咔啉-3-羧酰胺系列（18-23）的衍生物显示出对神经胶质瘤（U251）和卵巢癌（OVCAR-3）的强活性和高选择
• Synthesis and antitumor activity of novel 1-substituted phenyl 3-(2-oxo-1,3,4-oxadiazol-5-yl) β-carbolines and their Mannich bases
  作者：Franciele Cristina Savariz、Mary Ann Foglio、Ana Lucia T. Goes Ruiz、Willian Ferreira da Costa、Marina de Magalhães Silva、Josué Carinhanha Caldas Santos、Isis Martins Figueiredo、Emerson Meyer、João Ernesto de Carvalho、Maria Helena Sarragiotto

  DOI：10.1016/j.bmc.2014.10.031

  日期：2014.12

  for their in vitro antitumor activity against seven human cancer cell lines. Compounds of 4a–e series showed a broad spectrum of antitumor activity, with GI50 values lower than 15 μM for five cell lines. The derivative 4b, having the N,N-dimethylaminophenyl group at C-1, displayed the highest activity with GI50 in the range of 0.67–3.20 μM. A high selectivity and potent activity were observed for some

  一系列新型的1-（取代的苯基）-3-（2-氧代-1,3,4-恶二唑-5-基）β-咔啉（4a – e）和相应的曼尼希碱5 – 9（a – c合成）并评估其对七种人类癌细胞系的体外抗肿瘤活性。4a – e系列化合物显示出广泛的抗肿瘤活性，五个细胞系的GI 50值低于15μM。在C-1处具有N，N-二甲基氨基苯基的衍生物4b在GI 50下表现出最高的活性在0.67–3.20μM的范围内。观察到某些Mannich碱基具有较高的选择性和强活性，特别是对耐药卵巢（NCI-ADR / RES）细胞系（5a，5b，6a，6c和9b）和卵巢（OVCAR-03）细胞系（5b，图6a，6c，9a，9b和9c）。另外，通过使用UV和荧光光谱分析研究了化合物4b与DNA的相互作用。这些研究表明4b通过插入结合与ctDNA相互作用。
• Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) β-carboline derivatives
  作者：Anelise S. Nazari Formagio、Lilian T. Düsman Tonin、Mary Ann Foglio、Christiana Madjarof、João Ernesto de Carvalho、Willian Ferreira da Costa、Flávia P. Cardoso、Maria Helena Sarragiotto

  DOI：10.1016/j.bmc.2008.10.008

  日期：2008.11

  Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50) < 100 mu M) for all eight different types of human cancer cell lines tested. The b-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI50 values lying in the nanomolar concentration range (GI(50) = 10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50) = 0.06 mu M), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents. (C) 2008 Elsevier Ltd. All rights reserved.