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J., Fenwick A., Savioli L., Molyneux D. H., <i>Lancet<\/i>, <b>373<\/b>, 1570\u20131575 (2009).","DOI":"10.1016\/S0140-6736(09)60233-6"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Steverding D., <i>Parasit. Vectors<\/i>, <b>7<\/b>, 317 (2014).","DOI":"10.1186\/1756-3305-7-317"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Simarro P. P., Cecchi G., Franco J. R., Paone M., Diarra A., Ruiz-Postigo J. A., Fevre E. M., Mattioli R. C., Jannin J. G., <i>PLoS Negl. Trop. Dis.<\/i>, <b>6<\/b>, e1859 (2012).","DOI":"10.1371\/journal.pntd.0001859"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Alvar J., V\u00e9lez I. D., Bern C., Herrero M., Desjeux P., Cano J., Jannin J., den Boer M., WHO Leishmaniasis Control Team, <i>PLoS ONE<\/i>, <b>7<\/b>, e35671 (2012).","DOI":"10.1371\/journal.pone.0035671"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Fivelman Q. L., Yardley V., Sutherland C. 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Rev.<\/i>, <b>23<\/b>, 456\u2013487 (2003).","DOI":"10.1002\/med.10040"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Miyata J., Nakashima H., Nemoto H., Kim H.-S., Wataya Y., Ihara M., <i>Heterocycles<\/i>, <b>49<\/b>, 101\u2013104 (1998).","DOI":"10.3987\/COM-98-S46"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Takasu K., Katagiri R., Tanaka Y., Toyota M., Kim H.-S., Wataya Y., Ihara M., <i>Heterocycles<\/i>, <b>54<\/b>, 607\u2013610 (2001).","DOI":"10.3987\/COM-00-S(I)91"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Fujishima H., Takeshita H., Toyota M., Kim H.-S., Wataya Y., Tanaka M., Sasaki T., Ihara M., <i>Chem. Pharm. Bull.<\/i>, <b>49<\/b>, 572\u2013575 (2001).","DOI":"10.1248\/cpb.49.572"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Kawakami M., Koya K., Ukai T., Tatsuta N., Ikegawa A., Ogawa K., Shishido T., Chen L. B., <i>J. Med. Chem.<\/i>, <b>41<\/b>, 130\u2013142 (1998).","DOI":"10.1021\/jm970590k"},{"key":"18","unstructured":"18) Koya K., Li Y., Wang H., Ukai T., Tatsuta N., Kawakami M., Shishido T., Chen L. B., <i>Cancer Res.<\/i>, <b>56<\/b>, 538\u2013543 (1996)."},{"key":"19","unstructured":"19) Britten C. D., Rowinsky E. K., Baker S. D., Weiss G. R., Smith L., Stephenson J., Rothenberg M., Smetzer L., Cramer J., Collins W., Von Hoff D. D., Eckhardt S., <i>Clin. Cancer Res.<\/i>, <b>6<\/b>, 42\u201349 (2000)."},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Chen L. B., <i>Annu. Rev. Cell Biol.<\/i>, <b>4<\/b>, 155\u2013181 (1988).","DOI":"10.1146\/annurev.cb.04.110188.001103"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Johnson L. V., Walsh M. L., Chen L. B., <i>Proc. Natl. Acad. Sci. U.S.A.<\/i>, <b>77<\/b>, 990\u2013994 (1980).","DOI":"10.1073\/pnas.77.2.990"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Modica-Napolitano J. S., Aprille J. R., <i>Adv. 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Neurosci.<\/i>, <b>4<\/b>, 930\u2013939 (2013).","DOI":"10.1021\/cn300210g"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Kim H.-S., Shibata Y., Wataya Y., Tsuchiya K., Masuyama A., Nojima M., <i>J. Med. Chem.<\/i>, <b>42<\/b>, 2604\u20132609 (1999).","DOI":"10.1021\/jm990014j"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Desjardins R. E., Canfield C. J., Haynes J. D., Chulay J. D., <i>Antimicrob. Agents Chemother.<\/i>, <b>16<\/b>, 710\u2013718 (1979).","DOI":"10.1128\/AAC.16.6.710"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Peters W., Portus J. H., Robinson B. L., <i>Ann. Trop. Med. Parasitol.<\/i>, <b>69<\/b>, 155\u2013171 (1975).","DOI":"10.1080\/00034983.1975.11686997"},{"key":"34","unstructured":"34) Peters W., Richards W. H. 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Ber.<\/i>, <b>102<\/b>, 3603\u20133604 (1969).","DOI":"10.1002\/cber.19691021040"},{"key":"54","unstructured":"54) Basic Blue 3 (<b>37a<\/b>) is commercially available from MP Biomedicals (purity: dye content <i>ca.<\/i> 60%). The <i>in vitro<\/i> evaluation of <b>37a<\/b> was carried out using synthetic one (&gt;95% purity), but the <i>in vivo<\/i> evaluation was done using purchased one (<i>ca.<\/i> 60% purity). Compounds <b>37b<\/b>\u2013<b>e<\/b> with high purity (&gt;95%) were used for <i>in vitro<\/i> and <i>in vivo<\/i> assays."},{"key":"55","doi-asserted-by":"crossref","unstructured":"55) Takasu K., Terauchi H., Inoue H., Takahashi M., Sekita S., Ihara M., <i>Heterocycles<\/i>, <b>64<\/b>, 215\u2013221 (2004).","DOI":"10.3987\/COM-04-S(P)14"},{"key":"56","doi-asserted-by":"crossref","unstructured":"56) Yang M., Arai C., Baker Md A., Lu J., Ge J.-F., Pudhom K., Takasu K., Kasai K., Kaiser M., Brun R., Yardley V., Itoh I., Ihara M., <i>J. Med. 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