EMICORON: A multi-targeting G4 ligand with a promising preclinical profile

Manuela Porru, Pasquale Zizza, Marco Franceschin, Carlo Leonetti, Annamaria Biroccio

Research output: Contribution to journalReview article

Abstract

BACKGROUND: During the last decade, guanine G-rich sequences folding into G-quadruplex (G4) structures have received a lot of attention and their biological role is now a matter of large debate. Rising amounts of experimental evidence have validated several G-rich motifs as molecular targets in cancer treatment. Despite that an increasing number of small molecules has been reported to possess excellent G4 stabilizing properties, none of them has progressed through the drug-development pipeline due to their poor drug-like properties. In this context, the identification of G4 ligands with more favorable pharmacological properties and with a well-defined target activity could be fruitful for anticancer therapy application.

SCOPE OF REVIEW: This manuscript outlines the current state of knowledge regarding EMICORON, a G4-interactive molecule structurally and biologically similar, on the one side, to coronene and, on the other side, to a bay-monosubstituted perylene.

MAJOR CONCLUSIONS: Overall this work evidences that EMICORON, a new promising G4 ligand, possesses a marked antitumoral activity both standing alone and in combination with chemotherapeutics. Moreover, EMICORON represents a good example of multimodal class of antitumoral drug, able to simultaneously affect multiple targets participating in several distinct signaling pathways, thus simplifying the treatment modalities and improving the selectivity against cancer cells.

GENERAL SIGNIFICANCE: Due to the importance of G4 forming sequences in crucial biological processes participating in tumor progression, their successful targeting with small molecules could represent a very important innovation in the development of effective therapeutic strategies against cancer. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

Original languageEnglish
Pages (from-to)1362-1370
Number of pages9
JournalBiochimica et Biophysica Acta - General Subjects
Volume1861
Issue number5 Pt B
DOIs
Publication statusPublished - May 2017

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G-Quadruplexes
Ligands
Molecules
Perylene
Pharmaceutical Preparations
Neoplasms
Oncology
Guanine
Biological Phenomena
Tumors
Pipelines
Innovation
Cells
Pharmacology
EMICORON
Therapeutics
coronene

Keywords

  • Animals
  • Antineoplastic Agents
  • Antineoplastic Combined Chemotherapy Protocols
  • Binding Sites
  • Cell Proliferation
  • DNA, Neoplasm
  • Drug Design
  • G-Quadruplexes
  • Guanosine
  • Humans
  • Imides
  • Ligands
  • Models, Molecular
  • Neoplasms
  • Piperidines
  • Signal Transduction
  • Structure-Activity Relationship
  • Telomere
  • Tumor Burden
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Review

Cite this

EMICORON : A multi-targeting G4 ligand with a promising preclinical profile. / Porru, Manuela; Zizza, Pasquale; Franceschin, Marco; Leonetti, Carlo; Biroccio, Annamaria.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1861, No. 5 Pt B, 05.2017, p. 1362-1370.

Research output: Contribution to journalReview article

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abstract = "BACKGROUND: During the last decade, guanine G-rich sequences folding into G-quadruplex (G4) structures have received a lot of attention and their biological role is now a matter of large debate. Rising amounts of experimental evidence have validated several G-rich motifs as molecular targets in cancer treatment. Despite that an increasing number of small molecules has been reported to possess excellent G4 stabilizing properties, none of them has progressed through the drug-development pipeline due to their poor drug-like properties. In this context, the identification of G4 ligands with more favorable pharmacological properties and with a well-defined target activity could be fruitful for anticancer therapy application.SCOPE OF REVIEW: This manuscript outlines the current state of knowledge regarding EMICORON, a G4-interactive molecule structurally and biologically similar, on the one side, to coronene and, on the other side, to a bay-monosubstituted perylene.MAJOR CONCLUSIONS: Overall this work evidences that EMICORON, a new promising G4 ligand, possesses a marked antitumoral activity both standing alone and in combination with chemotherapeutics. Moreover, EMICORON represents a good example of multimodal class of antitumoral drug, able to simultaneously affect multiple targets participating in several distinct signaling pathways, thus simplifying the treatment modalities and improving the selectivity against cancer cells.GENERAL SIGNIFICANCE: Due to the importance of G4 forming sequences in crucial biological processes participating in tumor progression, their successful targeting with small molecules could represent a very important innovation in the development of effective therapeutic strategies against cancer. This article is part of a Special Issue entitled {"}G-quadruplex{"} Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.",
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author = "Manuela Porru and Pasquale Zizza and Marco Franceschin and Carlo Leonetti and Annamaria Biroccio",
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T1 - EMICORON

T2 - A multi-targeting G4 ligand with a promising preclinical profile

AU - Porru, Manuela

AU - Zizza, Pasquale

AU - Franceschin, Marco

AU - Leonetti, Carlo

AU - Biroccio, Annamaria

N1 - Copyright © 2016 Elsevier B.V. All rights reserved.

PY - 2017/5

Y1 - 2017/5

N2 - BACKGROUND: During the last decade, guanine G-rich sequences folding into G-quadruplex (G4) structures have received a lot of attention and their biological role is now a matter of large debate. Rising amounts of experimental evidence have validated several G-rich motifs as molecular targets in cancer treatment. Despite that an increasing number of small molecules has been reported to possess excellent G4 stabilizing properties, none of them has progressed through the drug-development pipeline due to their poor drug-like properties. In this context, the identification of G4 ligands with more favorable pharmacological properties and with a well-defined target activity could be fruitful for anticancer therapy application.SCOPE OF REVIEW: This manuscript outlines the current state of knowledge regarding EMICORON, a G4-interactive molecule structurally and biologically similar, on the one side, to coronene and, on the other side, to a bay-monosubstituted perylene.MAJOR CONCLUSIONS: Overall this work evidences that EMICORON, a new promising G4 ligand, possesses a marked antitumoral activity both standing alone and in combination with chemotherapeutics. Moreover, EMICORON represents a good example of multimodal class of antitumoral drug, able to simultaneously affect multiple targets participating in several distinct signaling pathways, thus simplifying the treatment modalities and improving the selectivity against cancer cells.GENERAL SIGNIFICANCE: Due to the importance of G4 forming sequences in crucial biological processes participating in tumor progression, their successful targeting with small molecules could represent a very important innovation in the development of effective therapeutic strategies against cancer. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

AB - BACKGROUND: During the last decade, guanine G-rich sequences folding into G-quadruplex (G4) structures have received a lot of attention and their biological role is now a matter of large debate. Rising amounts of experimental evidence have validated several G-rich motifs as molecular targets in cancer treatment. Despite that an increasing number of small molecules has been reported to possess excellent G4 stabilizing properties, none of them has progressed through the drug-development pipeline due to their poor drug-like properties. In this context, the identification of G4 ligands with more favorable pharmacological properties and with a well-defined target activity could be fruitful for anticancer therapy application.SCOPE OF REVIEW: This manuscript outlines the current state of knowledge regarding EMICORON, a G4-interactive molecule structurally and biologically similar, on the one side, to coronene and, on the other side, to a bay-monosubstituted perylene.MAJOR CONCLUSIONS: Overall this work evidences that EMICORON, a new promising G4 ligand, possesses a marked antitumoral activity both standing alone and in combination with chemotherapeutics. Moreover, EMICORON represents a good example of multimodal class of antitumoral drug, able to simultaneously affect multiple targets participating in several distinct signaling pathways, thus simplifying the treatment modalities and improving the selectivity against cancer cells.GENERAL SIGNIFICANCE: Due to the importance of G4 forming sequences in crucial biological processes participating in tumor progression, their successful targeting with small molecules could represent a very important innovation in the development of effective therapeutic strategies against cancer. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

KW - Animals

KW - Antineoplastic Agents

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Binding Sites

KW - Cell Proliferation

KW - DNA, Neoplasm

KW - Drug Design

KW - G-Quadruplexes

KW - Guanosine

KW - Humans

KW - Imides

KW - Ligands

KW - Models, Molecular

KW - Neoplasms

KW - Piperidines

KW - Signal Transduction

KW - Structure-Activity Relationship

KW - Telomere

KW - Tumor Burden

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Review

U2 - 10.1016/j.bbagen.2016.11.010

DO - 10.1016/j.bbagen.2016.11.010

M3 - Review article

C2 - 27838395

VL - 1861

SP - 1362

EP - 1370

JO - Biochimica et Biophysica Acta - General Subjects

JF - Biochimica et Biophysica Acta - General Subjects

SN - 0304-4165

IS - 5 Pt B

ER -