Biochimie, volume 133, pages 45-55

2-Guanidino-quinazolines as a novel class of translation inhibitors

Komarova Ekaterina S ¹

Osterman Ilya A ^{2, 3}

Pletnev P I ^{2, 3}

Ivanenkov Yan ^{2, 4, 5}

Majouga Alexander G. ^{2, 5}

Bogdanov Alexey A. ²

Sergiev Petr V. ^{2, 3}

Hide authors affiliations Show authors affiliations: 5 affiliations

Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119992, Russia. |

Chemistry Dept., Lomonosov Moscow State University, Moscow, 119991, Russia |

Skolkovo Institute of Science and Technology, Skolkovo, 143026, Russia |

⁴

Moscow Institute of Physics and Technology (State University), Moscow Region, 117303, Russia |

⁵

National University of Science and Technology (MISiS), Moscow, 119049, Russia |

Publication type: Journal Article

Publication date: 2017-02-01

Elsevier

Journal: Biochimie

Quartile SCImago

Quartile WOS

Impact factor: 3.9

ISSN: 03009084, 61831638

DOI: 10.1016/j.biochi.2016.11.008

Copy DOI

Biochemistry

General Medicine

Abstract

A variety of structurally unrelated organic compounds has been reported to have antibacterial activity. Among these, certain small-molecule translation inhibitors have attracted a great deal of attention, due to their relatively high selectivity against prokaryotes, and an appropriate therapeutic index with minor "off target" effects. However, ribosomes are being considered as poorly druggable biological targets, thereby making some routine computational-based approaches to rational drug design and its development rather ineffective. Taking this into account, diversity-oriented biological screening can reasonably be considered as the most advantageous strategy. Thus, using a high-throughput screening (HTS) platform, we applied a unique biological assay for in vitro evaluation of thousands of organic molecules, especially targeted against bacterial ribosomes and translation. As a result, we have identified a series of structurally diverse small-molecule compounds that induce a reporter strain sensitive to translation and DNA biosynthesis inhibitors. In a cell free system, several molecules were found to strongly inhibit protein biosynthesis. Among them, compounds bearing a 2-guanidino-quinazoline core demonstrated the most promising antibacterial activity. With regard to the preliminary structure-activity relationship (SAR) study, we revealed that relatively small substituents at positions 4, 6 and 8 of the quinazoline ring significantly enhance the target activity whereas modification of the guanidine group leads to decrease or loss of antibacterial potency. This novel class of translation inhibitors can properly be regarded as a promising starting point for the development of novel antibacterial therapeutic or screening tools.

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Citations by journals

	1 2
Combinatorial Chemistry and High Throughput Screening	Combinatorial Chemistry and High Throughput Screening, 2, 10% Combinatorial Chemistry and High Throughput Screening 2 publications, 10%
Bioorganic and Medicinal Chemistry Letters	Bioorganic and Medicinal Chemistry Letters, 2, 10% Bioorganic and Medicinal Chemistry Letters 2 publications, 10%
Nature Chemical Biology	Nature Chemical Biology, 1, 5% Nature Chemical Biology 1 publication, 5%
Anti-Infective Agents	Anti-Infective Agents, 1, 5% Anti-Infective Agents 1 publication, 5%
Journal of Antibiotics	Journal of Antibiotics, 1, 5% Journal of Antibiotics 1 publication, 5%
Pharmaceutical Chemistry Journal	Pharmaceutical Chemistry Journal, 1, 5% Pharmaceutical Chemistry Journal 1 publication, 5%
Frontiers in Microbiology	Frontiers in Microbiology, 1, 5% Frontiers in Microbiology 1 publication, 5%
Microorganisms	Microorganisms, 1, 5% Microorganisms 1 publication, 5%
European Journal of Pharmaceutical Sciences	European Journal of Pharmaceutical Sciences, 1, 5% European Journal of Pharmaceutical Sciences 1 publication, 5%
ChemMedChem	ChemMedChem, 1, 5% ChemMedChem 1 publication, 5%
Journal of Heterocyclic Chemistry	Journal of Heterocyclic Chemistry, 1, 5% Journal of Heterocyclic Chemistry 1 publication, 5%
Industrial & Engineering Chemistry Research	Industrial & Engineering Chemistry Research, 1, 5% Industrial & Engineering Chemistry Research 1 publication, 5%
Proceedings of the National Academy of Sciences of the United States of America	Proceedings of the National Academy of Sciences of the United States of America, 1, 5% Proceedings of the National Academy of Sciences of the United States of America 1 publication, 5%
Biomolecules	Biomolecules, 1, 5% Biomolecules 1 publication, 5%
RSC Medicinal Chemistry	RSC Medicinal Chemistry, 1, 5% RSC Medicinal Chemistry 1 publication, 5%
ACS Infectious Diseases	ACS Infectious Diseases, 1, 5% ACS Infectious Diseases 1 publication, 5%
Pharmaceuticals	Pharmaceuticals, 1, 5% Pharmaceuticals 1 publication, 5%
	1 2

Citations by publishers

	1 2 3
Springer Nature	Springer Nature, 3, 15% Springer Nature 3 publications, 15%
Bentham Science	Bentham Science, 3, 15% Bentham Science 3 publications, 15%
Elsevier	Elsevier, 3, 15% Elsevier 3 publications, 15%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 3, 15% Multidisciplinary Digital Publishing Institute (MDPI) 3 publications, 15%
Wiley	Wiley, 2, 10% Wiley 2 publications, 10%
American Chemical Society (ACS)	American Chemical Society (ACS), 2, 10% American Chemical Society (ACS) 2 publications, 10%
Frontiers Media S.A.	Frontiers Media S.A., 1, 5% Frontiers Media S.A. 1 publication, 5%
Proceedings of the National Academy of Sciences (PNAS)	Proceedings of the National Academy of Sciences (PNAS), 1, 5% Proceedings of the National Academy of Sciences (PNAS) 1 publication, 5%
Royal Society of Chemistry (RSC)	Royal Society of Chemistry (RSC), 1, 5% Royal Society of Chemistry (RSC) 1 publication, 5%
	1 2 3

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Komarova E. S. et al. 2-Guanidino-quinazolines as a novel class of translation inhibitors // Biochimie. 2017. Vol. 133. pp. 45-55.

GOST all authors (up to 50) Copy

Komarova E. S., Osterman I. A., Pletnev P. I., Ivanenkov Y., Majouga A. G., Bogdanov A. A., Sergiev P. V. 2-Guanidino-quinazolines as a novel class of translation inhibitors // Biochimie. 2017. Vol. 133. pp. 45-55.

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1016/j.biochi.2016.11.008

UR - https://doi.org/10.1016%2Fj.biochi.2016.11.008

TI - 2-Guanidino-quinazolines as a novel class of translation inhibitors

T2 - Biochimie

AU - Pletnev, P I

AU - Komarova, Ekaterina S

AU - Osterman, Ilya A

AU - Ivanenkov, Yan

AU - Majouga, Alexander G.

AU - Bogdanov, Alexey A.

AU - Sergiev, Petr V.

PY - 2017

DA - 2017/02/01 00:00:00

PB - Elsevier

SP - 45-55

VL - 133

SN - 0300-9084

SN - 6183-1638

ER -

BibTex

Cite this

BibTex Copy

@article{2017_Komarova,

author = {P I Pletnev and Ekaterina S Komarova and Ilya A Osterman and Yan Ivanenkov and Alexander G. Majouga and Alexey A. Bogdanov and Petr V. Sergiev},

title = {2-Guanidino-quinazolines as a novel class of translation inhibitors},

journal = {Biochimie},

year = {2017},

volume = {133},

publisher = {Elsevier},

month = {feb},

url = {https://doi.org/10.1016%2Fj.biochi.2016.11.008},

pages = {45--55},

doi = {10.1016/j.biochi.2016.11.008}

}

Found error?

Publisher

Elsevier

Journal

Biochimie

Quartile SCImago

Quartile WOS

Impact factor

3.9

ISSN

03009084 (Print)
61831638 (Electronic)

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