{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T06:07:08Z","timestamp":1760854028066},"reference-count":26,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[1999,8,1]],"date-time":"1999-08-01T00:00:00Z","timestamp":933465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[1999,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            6-Anilinouracils are selective inhibitors of DNA polymerase III, the enzyme required for the replication of chromosomal DNA in gram-positive bacteria (N. C. Brown, L. W. Dudycz, and G. E. Wright, Drugs Exp. Clin. Res. 12:555\u2013564, 1986). A new class of 6-anilinouracils based on N-3 alkyl substitution of the uracil ring was synthesized and analyzed for activity as inhibitors of the gram-positive bacterial DNA polymerase III and the growth of gram-positive bacterial pathogens. Favorable in vitro properties of N-3-alkyl derivatives prompted the synthesis of derivatives in which the R group at N-3 was replaced with more-hydrophilic methoxyalkyl and hydroxyalkyl groups. These hydroxyalkyl and methoxyalkyl derivatives displayed\n            <jats:italic>\n              K\n              <jats:sub>i<\/jats:sub>\n            <\/jats:italic>\n            values in the range from 0.4 to 2.8 \u03bcM against relevant gram-positive bacterial DNA polymerase IIIs and antimicrobial activity with MICs in the range from 0.5 to 15 \u03bcg\/ml against a broad spectrum of gram-positive bacteria, including methicillin-resistant staphylococci and vancomycin-resistant enterococci. Two of these hydrophilic derivatives displayed protective activity in a simple mouse model of lethal staphylococcal infection.\n          <\/jats:p>","DOI":"10.1128\/aac.43.8.1982","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:35:20Z","timestamp":1539045320000},"page":"1982-1987","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Inhibitors of DNA Polymerase III as Novel Antimicrobial Agents against Gram-Positive Eubacteria"],"prefix":"10.1128","volume":"43","author":[{"suffix":"Jr.","given":"Paul M.","family":"Tarantino","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester, Massachusetts 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengxin","family":"Zhi","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester, Massachusetts 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George E.","family":"Wright","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester, Massachusetts 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neal C.","family":"Brown","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester, Massachusetts 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1093\/nar\/6.3.1203","article-title":"Antibody to B. subtilis DNA polymerase III: use in the purification of enzyme and the study of its structure.","volume":"6","author":"Barnes M. 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