{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:19:21Z","timestamp":1789665561562,"version":"4.0.1"},"reference-count":22,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Grant Agency of Charles University with Project","award":["349 721"],"award-info":[{"award-number":["349 721"]}]},{"name":"the Grant Agency of Charles University with Project","award":["20-19638Y"],"award-info":[{"award-number":["20-19638Y"]}]},{"name":"the Grant Agency of Charles University with Project","award":["NU21-05-00482"],"award-info":[{"award-number":["NU21-05-00482"]}]},{"DOI":"10.13039\/501100001824","name":"the Czech Science Foundation","doi-asserted-by":"publisher","award":["349 721"],"award-info":[{"award-number":["349 721"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001824","name":"the Czech Science Foundation","doi-asserted-by":"publisher","award":["20-19638Y"],"award-info":[{"award-number":["20-19638Y"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001824","name":"the Czech Science Foundation","doi-asserted-by":"publisher","award":["NU21-05-00482"],"award-info":[{"award-number":["NU21-05-00482"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003243","name":"the Ministry of Health of the Czech Republic","doi-asserted-by":"publisher","award":["349 721"],"award-info":[{"award-number":["349 721"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003243","name":"the Ministry of Health of the Czech Republic","doi-asserted-by":"publisher","award":["20-19638Y"],"award-info":[{"award-number":["20-19638Y"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003243","name":"the Ministry of Health of the Czech Republic","doi-asserted-by":"publisher","award":["NU21-05-00482"],"award-info":[{"award-number":["NU21-05-00482"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Multidrug-resistant tuberculosis (MDR-TB) poses a significant threat to mankind and as such earned its place on the WHO list of priority pathogens. New antimycobacterials with a mechanism of action different to currently used agents are highly required. This study presents the design, synthesis, and biological evaluation of 3-acylaminopyrazine-2-carboxamides derived from a previously reported inhibitor of human prolyl-tRNA synthetase. Compounds were evaluated in vitro against various strains of mycobacteria, pathogenic bacteria, and fungi of clinical significance. In general, high activity against mycobacteria was noted, while the antibacterial and antifungal activity was minimal. The most active compounds were 4\u2019-substituted 3-(benzamido)pyrazine-2-carboxamides, exerting MIC (Minimum Inhibitory Concentration) from 1.95 to 31.25 \u00b5g\/mL. Detailed structure\u2013activity relationships were established and rationalized in silico with regard to mycobacterial ProRS as a probable target. The active compounds preserved their activity even against multidrug-resistant strains of Mycobacterium tuberculosis. At the same time, they were non-cytotoxic against HepG2 human hepatocellular carcinoma cells. This project is the first step in the successful repurposing of inhibitors of human ProRS to inhibitors of mycobacterial ProRS with antimycobacterial activity.<\/jats:p>","DOI":"10.3390\/biom12111561","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T07:17:48Z","timestamp":1666768668000},"page":"1561","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Adenosine-Mimicking Derivatives of 3-Aminopyrazine-2-Carboxamide: Towards Inhibitors of Prolyl-tRNA Synthetase with Antimycobacterial Activity"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3327-3078","authenticated-orcid":false,"given":"Vinod Sukanth Kumar","family":"Pallabothula","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Ak. Heyrovsk\u00e9ho 1203\/8, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5850-5381","authenticated-orcid":false,"given":"Marek","family":"Kerda","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Ak. Heyrovsk\u00e9ho 1203\/8, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-9082","authenticated-orcid":false,"given":"Martin","family":"Juh\u00e1s","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Ak. Heyrovsk\u00e9ho 1203\/8, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4633-2062","authenticated-orcid":false,"given":"Ond\u0159ej","family":"Jan\u010fourek","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Ak. Heyrovsk\u00e9ho 1203\/8, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5670-7767","authenticated-orcid":false,"given":"Kl\u00e1ra","family":"Kone\u010dn\u00e1","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Ak. 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