Lipophilic methylene violet analogues as modulators of mitochondrial function and dysfunction

Sandipan Roy Chowdhury, Omar Khdour, Indrajit Bandyopadhyay, Sidney Hecht

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

In an effort to identify methylene blue analogues having improved antioxidant activity, a series of new methylene violet analogues have been designed and synthesized. The analogues were prepared following a synthetic route that is more efficient than the previously reported methods, both in terms of yield and purity of the final products. The route involves the Smiles rearrangement as one of the crucial steps. Smiles rearrangement of suitably substituted diphenyl sulfide intermediates afforded the corresponding phenothiazine analogues in high yields, which were subsequently converted to the final products. The methylene violet analogues were evaluated for their ability to preserve mitochondrial function in Friedreich's ataxia (FRDA) lymphocytes. The analogues were shown to be efficient ROS scavengers, and able to protect cultured FRDA lymphocytes from oxidative stress resulting from inhibition of complex I. The analogues also preserved mitochondrial membrane potential and augmented ATP production. The analogues were found to be better antioxidants than the parent compounds methylene blue and methylene violet.

Original languageEnglish (US)
Pages (from-to)5537-5547
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume25
Issue number20
DOIs
StatePublished - Oct 15 2017

Fingerprint

Modulators
Friedreich Ataxia
Lymphocytes
Methylene Blue
Antioxidants
Oxidative stress
Mitochondrial Membrane Potential
Oxidative Stress
Adenosine Triphosphate
Membranes
methylene violet
diphenyl sulfide
phenothiazine

Keywords

  • Cytoprotection
  • Friedreich's ataxia
  • Methylene blue
  • Methylene violet
  • Mitochondria
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Lipophilic methylene violet analogues as modulators of mitochondrial function and dysfunction. / Roy Chowdhury, Sandipan; Khdour, Omar; Bandyopadhyay, Indrajit; Hecht, Sidney.

In: Bioorganic and Medicinal Chemistry, Vol. 25, No. 20, 15.10.2017, p. 5537-5547.

Research output: Contribution to journalArticle

@article{7686aad5ded945679bc828c9a74fccbe,
title = "Lipophilic methylene violet analogues as modulators of mitochondrial function and dysfunction",
abstract = "In an effort to identify methylene blue analogues having improved antioxidant activity, a series of new methylene violet analogues have been designed and synthesized. The analogues were prepared following a synthetic route that is more efficient than the previously reported methods, both in terms of yield and purity of the final products. The route involves the Smiles rearrangement as one of the crucial steps. Smiles rearrangement of suitably substituted diphenyl sulfide intermediates afforded the corresponding phenothiazine analogues in high yields, which were subsequently converted to the final products. The methylene violet analogues were evaluated for their ability to preserve mitochondrial function in Friedreich's ataxia (FRDA) lymphocytes. The analogues were shown to be efficient ROS scavengers, and able to protect cultured FRDA lymphocytes from oxidative stress resulting from inhibition of complex I. The analogues also preserved mitochondrial membrane potential and augmented ATP production. The analogues were found to be better antioxidants than the parent compounds methylene blue and methylene violet.",
keywords = "Cytoprotection, Friedreich's ataxia, Methylene blue, Methylene violet, Mitochondria, Reactive oxygen species",
author = "{Roy Chowdhury}, Sandipan and Omar Khdour and Indrajit Bandyopadhyay and Sidney Hecht",
year = "2017",
month = "10",
day = "15",
doi = "10.1016/j.bmc.2017.08.021",
language = "English (US)",
volume = "25",
pages = "5537--5547",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "20",

}

TY - JOUR

T1 - Lipophilic methylene violet analogues as modulators of mitochondrial function and dysfunction

AU - Roy Chowdhury, Sandipan

AU - Khdour, Omar

AU - Bandyopadhyay, Indrajit

AU - Hecht, Sidney

PY - 2017/10/15

Y1 - 2017/10/15

N2 - In an effort to identify methylene blue analogues having improved antioxidant activity, a series of new methylene violet analogues have been designed and synthesized. The analogues were prepared following a synthetic route that is more efficient than the previously reported methods, both in terms of yield and purity of the final products. The route involves the Smiles rearrangement as one of the crucial steps. Smiles rearrangement of suitably substituted diphenyl sulfide intermediates afforded the corresponding phenothiazine analogues in high yields, which were subsequently converted to the final products. The methylene violet analogues were evaluated for their ability to preserve mitochondrial function in Friedreich's ataxia (FRDA) lymphocytes. The analogues were shown to be efficient ROS scavengers, and able to protect cultured FRDA lymphocytes from oxidative stress resulting from inhibition of complex I. The analogues also preserved mitochondrial membrane potential and augmented ATP production. The analogues were found to be better antioxidants than the parent compounds methylene blue and methylene violet.

AB - In an effort to identify methylene blue analogues having improved antioxidant activity, a series of new methylene violet analogues have been designed and synthesized. The analogues were prepared following a synthetic route that is more efficient than the previously reported methods, both in terms of yield and purity of the final products. The route involves the Smiles rearrangement as one of the crucial steps. Smiles rearrangement of suitably substituted diphenyl sulfide intermediates afforded the corresponding phenothiazine analogues in high yields, which were subsequently converted to the final products. The methylene violet analogues were evaluated for their ability to preserve mitochondrial function in Friedreich's ataxia (FRDA) lymphocytes. The analogues were shown to be efficient ROS scavengers, and able to protect cultured FRDA lymphocytes from oxidative stress resulting from inhibition of complex I. The analogues also preserved mitochondrial membrane potential and augmented ATP production. The analogues were found to be better antioxidants than the parent compounds methylene blue and methylene violet.

KW - Cytoprotection

KW - Friedreich's ataxia

KW - Methylene blue

KW - Methylene violet

KW - Mitochondria

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=85029429750&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029429750&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2017.08.021

DO - 10.1016/j.bmc.2017.08.021

M3 - Article

VL - 25

SP - 5537

EP - 5547

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 20

ER -