ISSN Print 2500–1094
ISSN Online 2542–1204
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)
ORIGINAL RESEARCH
Aminopyridine- and aminopyrimidine-based serine/threonine protein kinase inhibitors are drug candidates for treating drug-resistant tuberculosis
About authors
1 Laboratory of Bacterial Genetics, Department of Genetics and Biotechnology,
Vavilov Institute of General Genetics of RAS, Moscow, Russia
2 Novie Nauchnie Tekhnologii Ltd., Moscow, Russia
Correspondence should be addressed: Valery N. Danilenko
ul. Gubkina, d. 3, Moscow, Russia, 119991; ur.ggiv@direlav
About paper
Funding: this work was supported by the Ministry of Education and Science of the Russian Federation (Grant No. 14.576.21.0019 dated July 27, 2014; ID RFMEFI57614X0019).
Contribution of the authors to this work: Maslov DA — experiment planning, data collection, analysis and interpretation, drafting a manuscript; Bekker OB — experiment planning, data analysis and interpretation, drafting a manuscript; Alekseeva MG, Kniazeva LM, Mavletova DA — data collection, participation in drafting of a manuscript; Afanasyev II, Vasilevich NI — provision of compound under study, participation in drafting a manuscript; Danileno VN — experiment planning, data interpretation, participation in drafting of a manuscript.
Received: 2017-01-30
Accepted: 2017-02-11
Published online: 2017-03-13
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Fig. 1. Principle of Mycobacterium smegmatis aphVIII+ test system
KanR — increased resistance to kanamycin, KanS — reduced resistance to kanamycin, STPK — serine/threonine protein kinase. Detailed description is provided in the article.
Fig. 2. Diameter of bacterial growth inhibition halos around discs impregnated with aminopyridine- and aminopyrimidine-based compounds
The compounds were tested in the Mycobacterium smegmatis aphVIII+ test system at subinhibitory concentrations (nmol/disc; specified near the sample name) that do not produce a bacterial growth inhibition halo. Error bars represent standard deviation. Selected compounds are shown in red.
Fig. 3. Inhibition of phosphorylating activity of Mycobacterium tuberculosis PknA in vitro by compounds selected by the Mycobacterium smegmatis aphVIII+ test system
Error bars represent standard deviation. Positive control is shown in green. The most active compounds are shown in red.
Fig. 4. Chemical structures of aminopyridine- and aminopyrimidine-based compounds selected as potential antituberculosis agents
