2,3-dihydro-3,3-dimethylspiro[1H-4-oxanthracene-5,2'-oxiran]-10(5H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 2,3-dihydro-3,3-dimethylspiro[1H-4-oxanthracene-5,2'-oxiran]-10(5H)-one
• 英文别名: 2,2-dimethyl-3,4-dihydrospiro[benzo[g]chromene-10,20-oxiran]-5(2H)-one；epoxy-α-lapachone；Epoxy-Alpha-Lapachone；2,2-dimethylspiro[3,4-dihydrobenzo[g]chromene-10,2'-oxirane]-5-one
• 化学式: C₁₆H₁₆O₃
• 分子量: 256.301
• InChiKey: XGFZRMCJSKBFKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  重氮甲烷 、 ALPHA-拉杷醌 以 乙醚 为溶剂， 反应 48.0h， 生成 2,3-dihydro-3,3-dimethylspiro[1H-4-oxanthracene-5,2'-oxiran]-10(5H)-one
  参考文献：
  名称：

  Trypanocidal agents with low cytotoxicity to mammalian cell line: A comparison of the theoretical and biological features of lapachone derivatives

  摘要：

  Starting from alpha- and beta-lapachones, in this work we compared the biological and theoretical profile of several oxyran derivatives of lapachone as potential trypanocidal agents. Our biological results showed that the oxyrans tested act as trypanocidal agents against Trypanosoma cruzi with minimal cytotoxicity in the VERO cell line compared to naphthoquinones. The oxyran derivative of alpha-lapachone (7a) showed to be one of the most potent compounds. In our molecular modeling study, we analyzed the C-ring moiety and the redox center of beta-lapachone molecule as the moieties responsible for the trypanocidal and cytotoxic effects on mammalian cell line. The computational methods used to delineate the structural requirements for the trypanocidal profile pointed out that the transposition of the C-ring moiety of beta-lapachone, combined with its oxyran ring, introduced important molecular requirements for trypanocidal activity in the HOMO energy, HOMO orbital coefficient, LUMO density, electrostatic potential map, dipole moment vector, and calculated logP (c logP) parameter. This study could lead to the development of new antichagasic medicines based on alpha-lapachone analogs. (c) D2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.04.046

文献信息

• New oxirane derivatives of 1,4-naphthoquinones and their evaluation against T. cruzi epimastigote forms
  作者：Paula F. Carneiro、Samara B. do Nascimento、Antonio V. Pinto、Maria do Carmo F.R. Pinto、Guilherme C. Lechuga、Dilvani O. Santos、Helvécio M. dos Santos Júnior、Jackson A.L.C. Resende、Saulo C. Bourguignon、Vitor F. Ferreira

  DOI：10.1016/j.bmc.2012.06.027

  日期：2012.8

  New oxirane derivatives were synthesized using six naphthoquinones as the starting materials. Our biological results showed that these oxiranes acted as trypanocidal agents against Trypanosoma cruzi with minimal cytotoxicity in the VERO cell line compared to naphthoquinones. In particular, oxirane derivative 14 showed low cytotoxicity in a mammalian cell line and exhibited better activity against epimastigote forms of T. cruzi than the current drug used to treat Chagas disease, benznidazole. (C) 2012 Elsevier Ltd. All rights reserved.
• 2,3-Dihydro-3,3-dimethylspiro[1<i>H</i>-4-oxanthracene-5,2′-oxiran]-10(5<i>H</i>)-one
  作者：Vitor F. Ferreira、Antonio V. Pinto、Maria C. R. F. Pinto、Milton N. da Silva、Janet M. S. Skakle、Maria C. B. V. de Souza、Solange M. S. V. Wardell

  DOI：10.1107/s0108270102013665

  日期：2002.9.15

  The central six-membered ring in the title compound, C16H16O3, is almost planar (and almost coplanar with the aromatic ring), despite one of its C atoms being formally sp(3) hybridized. The planarity is a consequence of the C atom at the centre of the spirocyclic system also being part of the three-membered epoxide ring. The molecules are linked by pi-pi and C-H ... pi interactions.
• Synthesis and antimalarial activity of quinones and structurally-related oxirane derivatives
  作者：Paula F. Carneiro、Maria C.R.F. Pinto、Roberta K.F. Marra、Fernando de C. da Silva、Jackson A.L.C. Resende、Luiz F. Rocha e Silva、Hilkem G. Alves、Gleyce S. Barbosa、Marne C. de Vasconcellos、Emerson S. Lima、Adrian M. Pohlit、Vitor F. Ferreira

  DOI：10.1016/j.ejmech.2015.11.020

  日期：2016.1

  A series of eighteen quinones and structurally-related oxiranes were synthesized and evaluated for in vitro inhibitory activity against the chloroquine-sensitive 3D7 clone of the human malaria parasite Plasmodium falciparum. 2-amino and 2-allyloxynaphthoquinones exhibited important antiplasmodial activity (median inhibitory concentrations (IC50) < 10 mu M). Oxiranes 6 and 25, prepared respectively by reaction of alpha-lapachone and tetrachloro-p-quinone with diazomethane in a mixture of ether and ethanol, exhibited the highest antiplasmodial activity and low cytotoxicity against human fibroblasts (MCR-5 cell line). The active compounds could represent a good prototype for an antimalarial lead molecule. (C) 2015 Published by Elsevier Masson SAS.
• Trypanocidal agents with low cytotoxicity to mammalian cell line: A comparison of the theoretical and biological features of lapachone derivatives
  作者：Vitor F. Ferreira、Alessandra Jorqueira、Alessandra M.T. Souza、Milton N. da Silva、Maria C.B.V. de Souza、Robson M. Gouvêa、Carlos R. Rodrigues、Antonio V. Pinto、Helena C. Castro、Dilvani O. Santos、Humberto P. Araújo、Saulo C. Bourguignon

  DOI：10.1016/j.bmc.2006.04.046

  日期：2006.8

  Starting from alpha- and beta-lapachones, in this work we compared the biological and theoretical profile of several oxyran derivatives of lapachone as potential trypanocidal agents. Our biological results showed that the oxyrans tested act as trypanocidal agents against Trypanosoma cruzi with minimal cytotoxicity in the VERO cell line compared to naphthoquinones. The oxyran derivative of alpha-lapachone (7a) showed to be one of the most potent compounds. In our molecular modeling study, we analyzed the C-ring moiety and the redox center of beta-lapachone molecule as the moieties responsible for the trypanocidal and cytotoxic effects on mammalian cell line. The computational methods used to delineate the structural requirements for the trypanocidal profile pointed out that the transposition of the C-ring moiety of beta-lapachone, combined with its oxyran ring, introduced important molecular requirements for trypanocidal activity in the HOMO energy, HOMO orbital coefficient, LUMO density, electrostatic potential map, dipole moment vector, and calculated logP (c logP) parameter. This study could lead to the development of new antichagasic medicines based on alpha-lapachone analogs. (c) D2006 Elsevier Ltd. All rights reserved.