Journal of Medicinal Chemistry, volume 61, issue 7, pages 2753-2775
Structure Guided Lead Generation toward Nonchiral M. tuberculosis Thymidylate Kinase Inhibitors
Song Lijun
1
,
Merceron Romain
2, 3
,
Gracia Begoña
4, 5
,
Lucía Quintana Ainhoa
4, 5
,
Risseeuw Martijn
1
,
Hulpia Fabian
1
,
Cos Paul
6
,
A. Ainsa Jose
4, 5
,
Munier-Lehmann Hélène
7
,
Savvides Savvas N.
2, 3
,
2
VIB Center for Inflammation Research, Zwijnaarde, Ghent 9052, Belgium
|
4
Grupo de Genética de Micobacterias, Departamento de Microbiología, Facultad de Medicina, and BIFI, Universidad de Zaragoza, Zaragoza, Spain
|
5
Ciber Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain
|
7
Unit of Chemistry and Biocatalysis, Department of Structural Biology and Chemistry, Institut Pasteur, CNRS UMR3523, 28 Rue du Dr. Roux, Cedex 15 75724 Paris, France
|
Publication type: Journal Article
Publication date: 2018-03-06
Journal:
Journal of Medicinal Chemistry
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 7.3
ISSN: 00222623, 15204804
Drug Discovery
Molecular Medicine
Abstract
In recent years, thymidylate kinase (TMPK), an enzyme indispensable for bacterial DNA biosynthesis, has been pursued for the development of new antibacterial agents including against Mycobacterium tuberculosis, the causative agent for the widespread infectious disease tuberculosis (TB). In response to a growing need for more effective anti-TB drugs, we have built upon our previous efforts toward the exploration of novel and potent Mycobacterium tuberculosis TMPK ( MtTMPK) inhibitors, and reported here the design of a novel series of non-nucleoside inhibitors of MtTMPK. The inhibitors display hitherto unexplored interactions in the active site of MtTMPK, offering new insights into structure-activity relationships. To investigate the discrepancy between enzyme inhibitory activity and the whole-cell activity, experiments with efflux pump inhibitors and efflux pump knockout mutants were performed. The minimum inhibitory concentrations of particular inhibitors increased significantly when determined for the efflux pump mmr knockout mutant, which partly explains the observed dissonance.
Citations by journals
|
1
2
3
4
|
|
|
European Journal of Medicinal Chemistry
|
European Journal of Medicinal Chemistry
4 publications, 15.38%
|
|
Journal of Medicinal Chemistry
|
Journal of Medicinal Chemistry
3 publications, 11.54%
|
|
Molecules
|
Molecules
2 publications, 7.69%
|
|
ChemistrySelect
|
ChemistrySelect
2 publications, 7.69%
|
|
Journal of Agricultural and Food Chemistry
|
Journal of Agricultural and Food Chemistry
2 publications, 7.69%
|
|
Combinatorial Chemistry and High Throughput Screening
|
Combinatorial Chemistry and High Throughput Screening
1 publication, 3.85%
|
|
Chemistry Africa
|
Chemistry Africa
1 publication, 3.85%
|
|
Current Pharmaceutical Design
|
Current Pharmaceutical Design
1 publication, 3.85%
|
|
Canadian Journal of Chemistry
|
Canadian Journal of Chemistry
1 publication, 3.85%
|
|
Bioorganic Chemistry
|
Bioorganic Chemistry
1 publication, 3.85%
|
|
PLoS ONE
|
PLoS ONE
1 publication, 3.85%
|
|
Journal of Organic Chemistry
|
Journal of Organic Chemistry
1 publication, 3.85%
|
|
Organic and Biomolecular Chemistry
|
Organic and Biomolecular Chemistry
1 publication, 3.85%
|
|
Journal of Enzyme Inhibition and Medicinal Chemistry
|
Journal of Enzyme Inhibition and Medicinal Chemistry
1 publication, 3.85%
|
|
Drug Design, Development and Therapy
|
Drug Design, Development and Therapy
1 publication, 3.85%
|
|
European Journal of Organic Chemistry
|
European Journal of Organic Chemistry
1 publication, 3.85%
|
|
Applied Biochemistry and Microbiology
|
Applied Biochemistry and Microbiology
1 publication, 3.85%
|
|
Current Organic Synthesis
|
Current Organic Synthesis
1 publication, 3.85%
|
|
1
2
3
4
|
Citations by publishers
|
1
2
3
4
5
6
|
|
|
American Chemical Society (ACS)
|
American Chemical Society (ACS)
6 publications, 23.08%
|
|
Elsevier
|
Elsevier
5 publications, 19.23%
|
|
Bentham Science
|
Bentham Science
3 publications, 11.54%
|
|
Wiley
|
Wiley
3 publications, 11.54%
|
|
Multidisciplinary Digital Publishing Institute (MDPI)
|
Multidisciplinary Digital Publishing Institute (MDPI)
2 publications, 7.69%
|
|
Springer Nature
|
Springer Nature
1 publication, 3.85%
|
|
Canadian Science Publishing
|
Canadian Science Publishing
1 publication, 3.85%
|
|
Public Library of Science (PLoS)
|
Public Library of Science (PLoS)
1 publication, 3.85%
|
|
Royal Society of Chemistry (RSC)
|
Royal Society of Chemistry (RSC)
1 publication, 3.85%
|
|
Taylor & Francis
|
Taylor & Francis
1 publication, 3.85%
|
|
Dove Medical Press
|
Dove Medical Press
1 publication, 3.85%
|
|
Pleiades Publishing
|
Pleiades Publishing
1 publication, 3.85%
|
|
1
2
3
4
5
6
|
- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
{"yearsCitations":{"type":"bar","data":{"show":true,"labels":[2019,2020,2021,2022,2023,2024],"ids":[0,0,0,0,0,0],"codes":[0,0,0,0,0,0],"imageUrls":["","","","","",""],"datasets":[{"label":"Citations number","data":[5,9,6,0,5,1],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":["19.23","34.62","23.08",0,"19.23","3.85"],"barThickness":null}]},"options":{"indexAxis":"x","maintainAspectRatio":true,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":1,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Citations per year","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"journals":{"type":"bar","data":{"show":true,"labels":["European Journal of Medicinal Chemistry","Journal of Medicinal Chemistry","Molecules","ChemistrySelect","Journal of Agricultural and Food Chemistry","Combinatorial Chemistry and High Throughput Screening","Chemistry Africa","Current Pharmaceutical Design","Canadian Journal of Chemistry","Bioorganic Chemistry","PLoS ONE","Journal of Organic Chemistry","Organic and Biomolecular Chemistry","Journal of Enzyme Inhibition and Medicinal Chemistry","Drug Design, Development and Therapy","European Journal of Organic Chemistry","Applied Biochemistry and Microbiology","Current Organic Synthesis"],"ids":[8171,3673,1770,8021,22576,13844,26931,12406,21147,4196,24963,8697,541,864,24856,19472,12511,20129],"codes":[0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0],"imageUrls":["\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/iLiQsFqFaSEx6chlGQ5fbAwF6VYU3WWa08hkss0g_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/bRyGpdm98BkAUYiK1YFNpl5Z7hPu6Gd87gbIeuG3_medium.webp","\/storage\/images\/resized\/iLiQsFqFaSEx6chlGQ5fbAwF6VYU3WWa08hkss0g_medium.webp","\/storage\/images\/resized\/doUaFUZdxUEQjLi1TwZjGHi8HXYNWWSk04dSC6Xh_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/doUaFUZdxUEQjLi1TwZjGHi8HXYNWWSk04dSC6Xh_medium.webp","\/storage\/images\/resized\/qZfu8vVyaDIo81Au73p6SNE8AGGzf73yfiTC33bu_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/PRGhlgB4OKRltSNtT39eA6wlnOTGRap1QQ6FQHih_medium.webp","\/storage\/images\/resized\/iLiQsFqFaSEx6chlGQ5fbAwF6VYU3WWa08hkss0g_medium.webp","\/storage\/images\/resized\/leiAYcRDGTSl5B1eCnwpSGqmDEUEfDPPoYisFGhT_medium.webp","\/storage\/images\/resized\/5YZtvLvkPZuc2JHOaZsjCvGSHFCuC3drUwN3YAc5_medium.webp","\/storage\/images\/resized\/wVWp6zaxUsMdR03dYMdOZoesUrVGtNMWkHKByIvT_medium.webp","\/storage\/images\/resized\/bRyGpdm98BkAUYiK1YFNpl5Z7hPu6Gd87gbIeuG3_medium.webp","\/storage\/images\/resized\/oZgeErrVFhuDksyqFURLvYS1wtVSBWczh001igGo_medium.webp","\/storage\/images\/resized\/doUaFUZdxUEQjLi1TwZjGHi8HXYNWWSk04dSC6Xh_medium.webp"],"datasets":[{"label":"","data":[4,3,2,2,2,1,1,1,1,1,1,1,1,1,1,1,1,1],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":[15.38,11.54,7.69,7.69,7.69,3.85,3.85,3.85,3.85,3.85,3.85,3.85,3.85,3.85,3.85,3.85,3.85,3.85],"barThickness":13}]},"options":{"indexAxis":"y","maintainAspectRatio":false,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":null,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Journals","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"publishers":{"type":"bar","data":{"show":true,"labels":["American Chemical Society (ACS)","Elsevier","Bentham Science","Wiley","Multidisciplinary Digital Publishing Institute (MDPI)","Springer Nature","Canadian Science Publishing","Public Library of Science (PLoS)","Royal Society of Chemistry (RSC)","Taylor & Francis","Dove Medical Press","Pleiades Publishing"],"ids":[40,17,39,11,202,8,6942,344,123,18,417,101],"codes":[0,0,0,0,0,0,0,0,0,0,0,0],"imageUrls":["\/storage\/images\/resized\/iLiQsFqFaSEx6chlGQ5fbAwF6VYU3WWa08hkss0g_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/doUaFUZdxUEQjLi1TwZjGHi8HXYNWWSk04dSC6Xh_medium.webp","\/storage\/images\/resized\/bRyGpdm98BkAUYiK1YFNpl5Z7hPu6Gd87gbIeuG3_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/qZfu8vVyaDIo81Au73p6SNE8AGGzf73yfiTC33bu_medium.webp","\/storage\/images\/resized\/PRGhlgB4OKRltSNtT39eA6wlnOTGRap1QQ6FQHih_medium.webp","\/storage\/images\/resized\/leiAYcRDGTSl5B1eCnwpSGqmDEUEfDPPoYisFGhT_medium.webp","\/storage\/images\/resized\/5YZtvLvkPZuc2JHOaZsjCvGSHFCuC3drUwN3YAc5_medium.webp","\/storage\/images\/resized\/wVWp6zaxUsMdR03dYMdOZoesUrVGtNMWkHKByIvT_medium.webp","\/storage\/images\/resized\/oZgeErrVFhuDksyqFURLvYS1wtVSBWczh001igGo_medium.webp"],"datasets":[{"label":"","data":[6,5,3,3,2,1,1,1,1,1,1,1],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":[23.08,19.23,11.54,11.54,7.69,3.85,3.85,3.85,3.85,3.85,3.85,3.85],"barThickness":13}]},"options":{"indexAxis":"y","maintainAspectRatio":false,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":null,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Publishers","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}}}
Metrics
Cite this
GOST |
RIS |
BibTex |
MLA
Cite this
GOST
Copy
Song L. et al. Structure Guided Lead Generation toward Nonchiral M. tuberculosis Thymidylate Kinase Inhibitors // Journal of Medicinal Chemistry. 2018. Vol. 61. No. 7. pp. 2753-2775.
GOST all authors (up to 50)
Copy
Song L., Merceron R., Gracia B., Lucía Quintana A., Risseeuw M., Hulpia F., Cos P., A. Ainsa J., Munier-Lehmann H., Savvides S. N., Van Calenbergh S. Structure Guided Lead Generation toward Nonchiral M. tuberculosis Thymidylate Kinase Inhibitors // Journal of Medicinal Chemistry. 2018. Vol. 61. No. 7. pp. 2753-2775.
Cite this
RIS
Copy
TY - JOUR
DO - 10.1021/acs.jmedchem.7b01570
UR - https://doi.org/10.1021%2Facs.jmedchem.7b01570
TI - Structure Guided Lead Generation toward Nonchiral M. tuberculosis Thymidylate Kinase Inhibitors
T2 - Journal of Medicinal Chemistry
AU - Song, Lijun
AU - Merceron, Romain
AU - Gracia, Begoña
AU - Van Calenbergh, Serge
AU - Lucía Quintana, Ainhoa
AU - Risseeuw, Martijn
AU - Hulpia, Fabian
AU - Cos, Paul
AU - A. Ainsa, Jose
AU - Munier-Lehmann, Hélène
AU - Savvides, Savvas N.
PY - 2018
DA - 2018/03/06 00:00:00
PB - American Chemical Society (ACS)
SP - 2753-2775
IS - 7
VL - 61
SN - 0022-2623
SN - 1520-4804
ER -
Cite this
BibTex
Copy
@article{2018_Song,
author = {Lijun Song and Romain Merceron and Begoña Gracia and Serge Van Calenbergh and Ainhoa Lucía Quintana and Martijn Risseeuw and Fabian Hulpia and Paul Cos and Jose A. Ainsa and Hélène Munier-Lehmann and Savvas N. Savvides},
title = {Structure Guided Lead Generation toward Nonchiral M. tuberculosis Thymidylate Kinase Inhibitors},
journal = {Journal of Medicinal Chemistry},
year = {2018},
volume = {61},
publisher = {American Chemical Society (ACS)},
month = {mar},
url = {https://doi.org/10.1021%2Facs.jmedchem.7b01570},
number = {7},
pages = {2753--2775},
doi = {10.1021/acs.jmedchem.7b01570}
}
Cite this
MLA
Copy
Song, Lijun, et al. “Structure Guided Lead Generation toward Nonchiral M. tuberculosis Thymidylate Kinase Inhibitors.” Journal of Medicinal Chemistry, vol. 61, no. 7, Mar. 2018, pp. 2753-2775. https://doi.org/10.1021%2Facs.jmedchem.7b01570.