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One of the mechanisms by which polyamine levels in AMs are elevated is enhanced uptake of exogenous polyamines. In this study, the possibility of targeting polyamine uptake as a treatment for PCP was examined. Four anthracene- and one benzene-polyamine conjugates that are potential polyamine transport inhibitors, including<jats:italic>N<\/jats:italic>1-anthracen-9-ylmethyl-butane-1,4-diamine;<jats:italic>N<\/jats:italic>-(4-aminobutyl)-<jats:italic>N<\/jats:italic>-anthracen-9-ylmethylbutane-1,4-diamine;<jats:italic>N<\/jats:italic>-[4-(4-aminobutylamino)butyl]-<jats:italic>N<\/jats:italic>-anthracen-9-ylmethylbutane-1,4-diamine;<jats:italic>N<\/jats:italic>-(4-amino-butyl)-<jats:italic>N<\/jats:italic>\u2032-(10-{[4-(4-amino-butylamino)butylamino]-methyl}anthracen-9-ylmethyl)butane-1,4-diamine (44-Ant-44); and benzene-polyamine conjugate<jats:italic>N<\/jats:italic>-(4-amino-butyl)-<jats:italic>N<\/jats:italic>\u2032-(4-{[4-(4-amino-butylamino)butylamino]-methyl}benzyl)butane-1,4-diamine (44-Bn-44), were tested. Compounds 44-Ant-44 and 44-Bn-44 were found to have a very low toxicity to AMs in vitro and were evaluated for their therapeutic effect on PCP in vivo. Sprague-Dawley rats infected with<jats:italic>P. carinii<\/jats:italic>for 28 days were intranasally instilled with 50 \u03bcl of a 1 mM solution of 44-Bn-44 or 44-Ant-44 every 2 days. Twenty-one days after initiation of the treatment, three to five rats from each group were sacrificed and examined for lung pathology, organism burden, and apoptosis of AMs. Both 44-Bn-44 and 44-Ant-44 reduced organism burdens; however, only 44-Ant-44 decreased the severity of the infection with reduced lung inflammation, increased clearance of exudates, increased air space, and decreased apoptosis of AMs. 44-Ant-44 also significantly prolonged the survival of treated animals. These results suggest that polyamine uptake is a potential target for treatment of PCP.<\/jats:p>","DOI":"10.1128\/aac.00662-09","type":"journal-article","created":{"date-parts":[[2009,10,6]],"date-time":"2009-10-06T01:21:07Z","timestamp":1254792067000},"page":"5259-5264","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Polyamine Transport as a Target for Treatment of<i>Pneumocystis<\/i>Pneumonia"],"prefix":"10.1128","volume":"53","author":[{"given":"Chung-Ping","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"IV","given":"Otto","family":"Phanstiel","sequence":"additional","affiliation":[{"name":"Department of Medical Education, University of Central Florida, Orlando, Florida 32816"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark E.","family":"Lasbury","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoujin","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202"},{"name":"Department of Obstetrics and Gynecology, Beijing Hospital, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela J.","family":"Durant","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bi-Hua","family":"Cheng","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Science, Chang Gung University and Department of Obstetrics and Gynecology, Kaohsiung Medical Center, Chang Gung Memorial Hospital, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Hung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202"},{"name":"Graduate Institute of Clinical Medical Science and Department of Laboratory Medicine, China Medical University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0022-3565(25)10541-7","volume":"274","year":"1995","unstructured":"Aziz, S. 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