Structure-activity relationships of furazano[3,4-b]pyrazines as mitochondrial uncouplers

被引：19
|
作者：
Kenwood, Brandon M. [1 ]
Calderone, Joseph A. [2 ,3 ]
Taddeo, Evan P. [1 ]
Hoehn, Kyle L. [1 ,4 ,5 ,6 ,7 ]
Santos, Webster L. [2 ,3 ]
机构：
[1] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA
[2] Virginia Tech, Dept Chem, Blacksburg, VA 24061 USA
[3] Virginia Tech, Virginia Tech Ctr Drug Discovery, Blacksburg, VA 24061 USA
[4] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA
[5] Univ Virginia, Cardiovasc Res Ctr, Charlottesville, VA 22908 USA
[6] Univ Virginia, Emily Cour Clin Canc Ctr, Charlottesville, VA 22908 USA
[7] Univ New S Wales, Dept Biotechnol & Biomol Sci, Kensington, NSW 2052, Australia
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 21期
关键词：
Mitochondrial uncoupler; Mitochondrial bioenergetics; Protonophore; Structure-activity relationships; Pyrazines; SUBSTITUTED PHENOLS; INSULIN-RESISTANCE; PLASMA-MEMBRANE; MECHANISM; PROTON; MODEL; FCCP; CELLS;
D O I：
10.1016/j.bmcl.2015.06.040
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Chemical mitochondrial uncouplers are lipophilic weak acids that transport protons into the mitochondrial matrix via a pathway that is independent of ATP synthase, thereby uncoupling nutrient oxidation from ATP production. These uncouplers have potential for the treatment of diseases such as obesity, Parkinson's disease, and aging. We have previously identified a novel mitochondrial protonophore, named BAM15, which stimulates mitochondrial respiration across a broad dosing range compared to carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). Herein, we report our investigations on the structure-activity relationship profile of BAM15. Our studies demonstrate the importance of the furazan, pyrazine, and aniline rings as well as pKa in maintaining its effective protonophore activity. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4858 / 4861
页数：4
相关论文
共 50 条
  • [31] Furoxano[3,4-b]pyrazines:: The first synthesis and X-ray structure
    Yudin, IL
    Sheremetev, AB
    Averkiev, BB
    Antipin, MY
    [J]. JOURNAL OF HETEROCYCLIC CHEMISTRY, 2005, 42 (04) : 691 - 694
  • [32] Synthesis and characterization of thieno[3,4-b]pyrazines.
    Sattler, DJ
    Funfar, MR
    Calhoun, TR
    Mitchell, KA
    Kenning, DD
    Rasmussen, SC
    [J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2001, 221 : U135 - U135
  • [33] The first synthesis of furazano[3,4-b] [1,6]naphthyridines
    Vasilev, Leonid S.
    Sheremetev, Aleksei B.
    Dorokhov, Vladimir A.
    Suponitsky, Kyrill Yu.
    [J]. JOURNAL OF HETEROCYCLIC CHEMISTRY, 2007, 44 (04) : 843 - 847
  • [34] Analgesic activity of 3,4-dichloromaleimides: structure-activity relationships
    Andricopulo, AD
    Willain, A
    Correa, R
    Santos, ARS
    Nunes, RJ
    Yunes, RA
    Cechinel, V
    [J]. PHARMAZIE, 1998, 53 (07): : 493 - 494
  • [35] Synthesis and anticonvulsant activity of some new pyrazolo[3,4-b]pyrazines and related heterocycles
    Farghaly, Abdel-Rahman
    Esmail, Sabah
    Abdel-Zaher, Ahmed
    Abdel-Hafez, Ali
    El-Kashef, Hussein
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2014, 22 (07) : 2166 - 2175
  • [36] Breast cancer growth and proliferation is suppressed by the mitochondrial targeted furazano[3,4-b]pyrazine BAM15
    Elizabeth R. M. Zunica
    Christopher L. Axelrod
    Eunhan Cho
    Guillaume Spielmann
    Gangarao Davuluri
    Stephanie J. Alexopoulos
    Martina Beretta
    Kyle L. Hoehn
    Wagner S. Dantas
    Krisztian Stadler
    William T. King
    Kathryn Pergola
    Brian A. Irving
    Ingeborg M. Langohr
    Shengping Yang
    Charles L. Hoppel
    L. Anne Gilmore
    John P. Kirwan
    [J]. Cancer & Metabolism, 9
  • [37] Breast cancer growth and proliferation is suppressed by the mitochondrial targeted furazano[3,4-b]pyrazine BAM15
    Zunica, Elizabeth R. M.
    Axelrod, Christopher L.
    Cho, Eunhan
    Spielmann, Guillaume
    Davuluri, Gangarao
    Alexopoulos, Stephanie J.
    Beretta, Martina
    Hoehn, Kyle L.
    Dantas, Wagner S.
    Stadler, Krisztian
    King, William T.
    Pergola, Kathryn
    Irving, Brian A.
    Langohr, Ingeborg M.
    Yang, Shengping
    Hoppel, Charles L.
    Gilmore, L. Anne
    Kirwan, John P.
    [J]. CANCER & METABOLISM, 2021, 9 (01)
  • [38] Comparative methods for the polymerization of thieno[3,4-b]pyrazines.
    Kenning, DD
    Rasmussen, SC
    [J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2002, 223 : B223 - B223
  • [39] Effects of chemical oxidants in the synthesis of polythieno[3,4-b]pyrazines
    Kenning, DD
    Rasmussen, SC
    [J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2004, 227 : U173 - U173
  • [40] 1,2,5-THIADIAZOLO[3,4-B]PYRAZINES
    TONG, YC
    [J]. JOURNAL OF HETEROCYCLIC CHEMISTRY, 1975, 12 (03) : 451 - 453
12345