(E)-3-(4-(N-(2-(thiophen-2-yl)methyl)sulfamoyl)phenyl)acrylic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(4-(N-(2-(thiophen-2-yl)methyl)sulfamoyl)phenyl)acrylic acid
• 英文别名: (E)-3-[4-(thiophen-2-ylmethylsulfamoyl)phenyl]prop-2-enoic acid
• 化学式: C₁₄H₁₃NO₄S₂
• 分子量: 323.394
• InChiKey: LAIQWQJXEIAYPM-VMPITWQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-(N-(2-(thiophen-2-yl)methyl)sulfamoyl)phenyl)acrylic acid 在 N-甲基吗啉 、 氯甲酸乙酯 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  In vitro and in vivo evaluation of novel cinnamyl sulfonamide hydroxamate derivative against colon adenocarcinoma

  摘要：

  The potential of cinnamic acid as an anti-inflammatory and anti-cancer agent has been studied previously. In our investigation, novel bio-isosters of cinnamyl sulfonamide hydroxamate were synthesized, characterized and confirmed for their structure and evaluated for cytotoxicity. Three NCEs namely, NMJ-1, -2 and -3 showed cell-growth inhibition in 6 human cancer cell lines with IC50 at the range of 3.3 +/- 0.15-44.9 +/- 2.6 mu M. The hydroxamate derivatives of cinnamyl sulfonamide are reported inhibitors of HDAC enzyme. Thus, the effectiveness of these molecules was determined by whole cell HDAC assay in HCT 116 cell line. NMJ-2 (0.41 +/- 0.01 mu M) exhibited better enzyme inhibition (IC50) compared to SAHA (2.63 +/- 0.07). In order to evaluate induction of apoptosis by treatment, Hoechst 33342 and AO/EB nuclear staining methods were used. Further, cell cycle analysis, Annexin V binding and caspase 3/7 activation assays were performed by flow cytometry where NMJ-2 significantly arrested the cell cycle at G(2)/M phase, increased Annexin V binding to the cell surface and activation of caspase-3/7. Bax/Bcl-2 ratio was observed by Western blot and showed an increase with NMJ-2 treatment. This was comparable to standard SAHA. The acute toxicity study (OECD-425) showed that NMJ-2 was safe up to 2000 mg/kg in rats. 1,2-Dimethyl hydrazine (DMH) was used to produce experimental colon adenocarcinoma in Wistar rats. 5-FU and NMJ-2 (100 mg/kg p.o. and 10 mg/kg i.p. once daily for 21 days, respectively) were administered to the respective groups. Both treatments significantly reduced ACFs, adenocarcinoma count, TNF-alpha, IL-6, nitrite and nitrate levels in colonic tissue. Our findings indicate that NMJ-2 has potent anti-cancer activity against colon cancer, by acting through HDAC enzyme inhibition and activation of intrinsic mitochondrial apoptotic pathway, with additional anti-inflammatory activity. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

  DOI：

  10.1016/j.cbi.2015.03.015
• 作为产物：
  描述：

  肉桂酸 在 碳酸氢钠 作用下， 以 水 为溶剂， 反应 8.0h， 生成 (E)-3-(4-(N-(2-(thiophen-2-yl)methyl)sulfamoyl)phenyl)acrylic acid
  参考文献：
  名称：

  In vitro and in vivo evaluation of novel cinnamyl sulfonamide hydroxamate derivative against colon adenocarcinoma

  摘要：

  The potential of cinnamic acid as an anti-inflammatory and anti-cancer agent has been studied previously. In our investigation, novel bio-isosters of cinnamyl sulfonamide hydroxamate were synthesized, characterized and confirmed for their structure and evaluated for cytotoxicity. Three NCEs namely, NMJ-1, -2 and -3 showed cell-growth inhibition in 6 human cancer cell lines with IC50 at the range of 3.3 +/- 0.15-44.9 +/- 2.6 mu M. The hydroxamate derivatives of cinnamyl sulfonamide are reported inhibitors of HDAC enzyme. Thus, the effectiveness of these molecules was determined by whole cell HDAC assay in HCT 116 cell line. NMJ-2 (0.41 +/- 0.01 mu M) exhibited better enzyme inhibition (IC50) compared to SAHA (2.63 +/- 0.07). In order to evaluate induction of apoptosis by treatment, Hoechst 33342 and AO/EB nuclear staining methods were used. Further, cell cycle analysis, Annexin V binding and caspase 3/7 activation assays were performed by flow cytometry where NMJ-2 significantly arrested the cell cycle at G(2)/M phase, increased Annexin V binding to the cell surface and activation of caspase-3/7. Bax/Bcl-2 ratio was observed by Western blot and showed an increase with NMJ-2 treatment. This was comparable to standard SAHA. The acute toxicity study (OECD-425) showed that NMJ-2 was safe up to 2000 mg/kg in rats. 1,2-Dimethyl hydrazine (DMH) was used to produce experimental colon adenocarcinoma in Wistar rats. 5-FU and NMJ-2 (100 mg/kg p.o. and 10 mg/kg i.p. once daily for 21 days, respectively) were administered to the respective groups. Both treatments significantly reduced ACFs, adenocarcinoma count, TNF-alpha, IL-6, nitrite and nitrate levels in colonic tissue. Our findings indicate that NMJ-2 has potent anti-cancer activity against colon cancer, by acting through HDAC enzyme inhibition and activation of intrinsic mitochondrial apoptotic pathway, with additional anti-inflammatory activity. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

  DOI：

  10.1016/j.cbi.2015.03.015

文献信息

• In vitro and in vivo evaluation of novel cinnamyl sulfonamide hydroxamate derivative against colon adenocarcinoma
  作者：Neetinkumar D. Reddy、M.H. Shoja、B.S. Jayashree、Pawan G. Nayak、Nitesh Kumar、V. Ganga Prasad、K. Sreedhara R. Pai、C. Mallikarjuna Rao

  DOI：10.1016/j.cbi.2015.03.015

  日期：2015.5

  The potential of cinnamic acid as an anti-inflammatory and anti-cancer agent has been studied previously. In our investigation, novel bio-isosters of cinnamyl sulfonamide hydroxamate were synthesized, characterized and confirmed for their structure and evaluated for cytotoxicity. Three NCEs namely, NMJ-1, -2 and -3 showed cell-growth inhibition in 6 human cancer cell lines with IC50 at the range of 3.3 +/- 0.15-44.9 +/- 2.6 mu M. The hydroxamate derivatives of cinnamyl sulfonamide are reported inhibitors of HDAC enzyme. Thus, the effectiveness of these molecules was determined by whole cell HDAC assay in HCT 116 cell line. NMJ-2 (0.41 +/- 0.01 mu M) exhibited better enzyme inhibition (IC50) compared to SAHA (2.63 +/- 0.07). In order to evaluate induction of apoptosis by treatment, Hoechst 33342 and AO/EB nuclear staining methods were used. Further, cell cycle analysis, Annexin V binding and caspase 3/7 activation assays were performed by flow cytometry where NMJ-2 significantly arrested the cell cycle at G(2)/M phase, increased Annexin V binding to the cell surface and activation of caspase-3/7. Bax/Bcl-2 ratio was observed by Western blot and showed an increase with NMJ-2 treatment. This was comparable to standard SAHA. The acute toxicity study (OECD-425) showed that NMJ-2 was safe up to 2000 mg/kg in rats. 1,2-Dimethyl hydrazine (DMH) was used to produce experimental colon adenocarcinoma in Wistar rats. 5-FU and NMJ-2 (100 mg/kg p.o. and 10 mg/kg i.p. once daily for 21 days, respectively) were administered to the respective groups. Both treatments significantly reduced ACFs, adenocarcinoma count, TNF-alpha, IL-6, nitrite and nitrate levels in colonic tissue. Our findings indicate that NMJ-2 has potent anti-cancer activity against colon cancer, by acting through HDAC enzyme inhibition and activation of intrinsic mitochondrial apoptotic pathway, with additional anti-inflammatory activity. (C) 2015 Elsevier Ireland Ltd. All rights reserved.