{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T05:37:08Z","timestamp":1760852228708},"reference-count":46,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2006,7,1]],"date-time":"2006-07-01T00:00:00Z","timestamp":1151712000000},"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":[[2006,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Bisbenzamidines, such as pentamidine isethionate, are aromatic dicationic compounds that are active against\n            <jats:italic>Pneumocystis<\/jats:italic>\n            and other microbes but are oftentimes toxic to the host. To identify potential anti-\n            <jats:italic>Pneumocystis<\/jats:italic>\n            agents, we synthesized bisbenzamidine derivatives in which the parent compound pentamidine was modified by a 1,4-piperazinediyl, alkanediamide, or 1,3-phenylenediamide moiety as the central linker. Several of the compounds were more active against\n            <jats:italic>P. carinii<\/jats:italic>\n            and less toxic than pentamidine in cytotoxicity assays. For this study, we evaluated nine bisbenzamidine derivatives representing a range of in vitro activities, from highly active to inactive, for the treatment of pneumocystosis in an immunosuppressed mouse model. Six of these in vitro-active compounds, 01, 02, 04, 06, 100, and 101, exhibited marked efficacies against infection at a dose of 10 mg\/kg of body weight, and four compounds, 01, 04, 100, and 101, showed significant increases in survival versus that of untreated infected control mice. Compound 100 was highly efficacious against the infection at 20 mg\/kg and 40 mg\/kg, with &gt;1,000-fold reductions in burden, and resulted in improved survival curves versus those for pentamidine-treated mice (at the same doses). All six bisbenzamidine compounds that exhibited high in vitro activity significantly decreased the infection in vivo; two compounds, 12 and 102, with marked to moderate in vitro activities had slight or no activity in vivo, while compound 31 was inactive in vitro and was also inactive in vivo. Thus, the selection of highly active compounds from in vitro cytotoxicity assays was predictive of activity in the mouse model of\n            <jats:italic>Pneumocystis<\/jats:italic>\n            pneumonia. We conclude that a number of these bisbenzamidine compounds, especially compound 100, may show promise as new anti-\n            <jats:italic>Pneumocystis<\/jats:italic>\n            drugs.\n          <\/jats:p>","DOI":"10.1128\/aac.00126-06","type":"journal-article","created":{"date-parts":[[2006,6,26]],"date-time":"2006-06-26T18:26:28Z","timestamp":1151346388000},"page":"2337-2343","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["In Vitro Selection and In Vivo Efficacy of Piperazine- and Alkanediamide-Linked Bisbenzamidines against\n            <i>Pneumocystis<\/i>\n            Pneumonia in Mice"],"prefix":"10.1128","volume":"50","author":[{"given":"Melanie T.","family":"Cushion","sequence":"first","affiliation":[{"name":"Research Service, Veterans Affairs Medical Center, Cincinnati, Ohio 45220"},{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0560"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter D.","family":"Walzer","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Medical Center, Cincinnati, Ohio 45220"},{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0560"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Ashbaugh","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Medical Center, Cincinnati, Ohio 45220"},{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0560"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Rebholz","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Medical Center, Cincinnati, Ohio 45220"},{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0560"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Brubaker","sequence":"additional","affiliation":[{"name":"The Christ Hospital, Department of Pathology, 2139 Auburn Avenue, Cincinnati, Ohio 45219"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Jacques","family":"Vanden Eynde","sequence":"additional","affiliation":[{"name":"Xavier University of Louisiana, College of Pharmacy, Division of Basic Pharmaceutical Sciences, New Orleans, Louisiana 10025"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annie","family":"Mayence","sequence":"additional","affiliation":[{"name":"Xavier University of Louisiana, College of Pharmacy, Division of Basic Pharmaceutical Sciences, New Orleans, Louisiana 10025"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tien L.","family":"Huang","sequence":"additional","affiliation":[{"name":"Xavier University of Louisiana, College of Pharmacy, Division of Basic Pharmaceutical Sciences, New Orleans, Louisiana 10025"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(00)00284-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.18.1.47"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1010.030981"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.12.2668"},{"key":"e_1_3_2_6_2","first-page":"273","volume":"1978","year":"1978","unstructured":"Bouchard, P., I. 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