{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:53:13Z","timestamp":1791359593235,"version":"4.3.1"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Emergence of drug\u2010resistant\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    necessitates the development of new drugs. Here, we studied the activity of new piperazine nitrofuranylamides against a collection of clinical strains from an multidrug\u2010resistant tuberculosis (MDR\u2010TB) high\u2010burden country. A series of nitrofuranylamides\n                    <jats:bold>9\u201315<\/jats:bold>\n                    was synthesized and evaluated using a collection of diverse clinical strains representing globally spread genotypes (Beijing, LAM, and Haarlem; susceptible, MDR, and pre\u2010extensively drug resistant). Minimal inhibitory concentrations (MIC) were determined using a resazurin assay. Whole\u2010genome sequencing was performed on an Illumina HiSeq platform. Although clinical isolates differed in their MICs, some tested compounds\u2014namely\n                    <jats:bold>11<\/jats:bold>\n                    and\n                    <jats:bold>12<\/jats:bold>\n                    \u2014showed higher MICs regardless of the clinical strain. In contrast, compounds\n                    <jats:bold>13\u201315<\/jats:bold>\n                    exhibited promising activity (MIC\u2009&lt;\u20090.1\u2009\u00b5g\/mL) against the majority of strains. Moreover,\n                    <jats:bold>13<\/jats:bold>\n                    and\n                    <jats:bold>14<\/jats:bold>\n                    were previously shown to have low toxicity in JCL:ICR mice and low cytotoxicity against human cell lines. A closer look at structural variation indicated that the presence of a pyridine\u2010 or quinoline\u2010type aryl substituent leads to a broader spectrum of activity. The additional nitro group in\n                    <jats:bold>14<\/jats:bold>\n                    appears to contribute significantly to its activity. A nonsynonymous mutation in the efflux pump gene\n                    <jats:italic>Rv3728<\/jats:italic>\n                    (372\u2009A\u2009&gt;\u2009V, GCC\u2009\u2192\u2009GTC) in one of the Haarlem genotype strains may speculatively correlate with its high\u2010level intrinsic resistance to nitrofurans. Further biological research is warranted to investigate the mechanism of action of the most promising compounds.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70355","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:31:33Z","timestamp":1791358293000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Evaluation of New Nitrofuranylamides With Collection of\n                    <i>Mycobacterium tuberculosis<\/i>\n                    Clinical Strains From Multidrug\u2010Resistant Tuberculosis High\u2010Burden Country"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0437-2162","authenticated-orcid":false,"given":"Georgi M.","family":"Dobrikov","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry with Centre of Phytochemistry Bulgarian Academy of Sciences Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Dogonadze","sequence":"additional","affiliation":[{"name":"St. Petersburg Research Institute of Phthisiopulmonology St. Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vyazovaya","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Epidemiology and Evolutionary Genetics St. Petersburg Pasteur Institute St. Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0052-8763","authenticated-orcid":false,"given":"Violeta","family":"Valcheva","sequence":"additional","affiliation":[{"name":"Stephan Angeloff Institute of Microbiology Bulgarian Academy of Sciences Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6906-6225","authenticated-orcid":false,"given":"Viacheslav","family":"Zhuravlev","sequence":"additional","affiliation":[{"name":"St. Petersburg Research Institute of Phthisiopulmonology St. Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5924-0576","authenticated-orcid":false,"given":"Igor","family":"Mokrousov","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Epidemiology and Evolutionary Genetics St. Petersburg Pasteur Institute St. Petersburg Russia"},{"name":"Henan International Joint Laboratory of Children's Infectious Diseases, Children's Hospital Affiliated to Zhengzhou University Henan Children's Hospital Zhengzhou Children's Hospital Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.chembiol.2019.10.010","article-title":"Antitubercular Triazines: Optimization and Intrabacterial Metabolism","volume":"27","author":"Wang X.","year":"2020","journal-title":"Cell Chemical Biology"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1007\/s40265-022-01817-w","article-title":"The Struggle to End a Millennia\u2010Long Pandemic: Novel Candidate and Repurposed Drugs for the Treatment of Tuberculosis","volume":"82","author":"Edwards B. D.","year":"2022","journal-title":"Drugs"},{"issue":"9","key":"e_1_2_8_4_1","doi-asserted-by":"crossref","DOI":"10.1128\/aac.00474-23","article-title":"Discovery and Characterization of Antimycobacterial Nitro\u2010Containing Compounds With Distinct Mechanisms of Action and In Vivo Efficacy","volume":"67","author":"Eke I. E.","year":"2023","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009663","article-title":"Nitrofurans: Revival of An \u2018Old\u2019 Drug Class in the Fight Against Antibiotic Resistance","volume":"17","author":"Le V. V. H.","year":"2021","journal-title":"PLoS Pathogens"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1021\/acsmedchemlett.5b00141","article-title":"Nitrofuranyl Methyl Piperazines as New Anti\u2010TB Agents: Identification, Validation, Medicinal Chemistry, and PK Studies","volume":"6","author":"Yempalla K. R.","year":"2015","journal-title":"ACS Medicinal Chemistry Letters"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ejmech.2019.01.050","article-title":"Attachment of a 5\u2010nitrofuroyl Moiety to Spirocyclic Piperidines Produces Non\u2010Toxic Nitrofurans That Are Efficacious In Vitro Against Multidrug\u2010Resistant Mycobacterium tuberculosis","volume":"166","author":"Krasavin M.","year":"2019","journal-title":"European Journal of Medicinal Chemistry"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26010207"},{"issue":"14","key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.3390\/molecules29143364","article-title":"Molecular Periphery Design Allows Control of the New Nitrofurans Antimicrobial Selectivity","volume":"29","author":"Vinogradova L.","year":"2024","journal-title":"Molecules"},{"key":"e_1_2_8_10_1","unstructured":"R. E.Lee R. P. Tangallapally R. Yendapally M. McNeil and A. 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