Aromatic diamidines as antiparasitic agents

Expert Opinion on Investigational Drugs

Volumn 14, Issue 8, 2005, Pages 957-972

  Soeiro, M N C ^a   De Souza, E M ^a   Stephens, C E ^b   Boykin, D W ^b  

^a INSTITUTO OSWALDO CRUZ   (Brazil)

^b GEORGIA STATE UNIVERSITY   (United States)

Author keywords

Aromatic diamidines; Chaga's disease; Chemotherapy; Leishmania; Malaria; Parasites; Trypanosomes

Indexed keywords

2,5 BIS(4 AMIDINOPHENYL)FURAN; ALLOPURINOL; AMPHOTERICIN B; ANTIMALARIAL AGENT; ANTIPARASITIC AGENT; ANTITRYPANOSOMAL AGENT; AROMATIC DIAMIDINE DERIVATIVE; BENZIMIDAZOLE; BIGUANIDE DERIVATIVE; CHLOROQUINE; COTRIMOXAZOLE; CPG 40215A; DB 289; DB 844; DIAMIDINE DERIVATIVE; DIMINAZENE ACETURATE; EFLORNITHINE; FLUCONAZOLE; FURAMIDINE DERIVATIVE; GAMMA INTERFERON; HEXAMIDINE ISETIONATE; MELARSOPROL; MILTEFOSINE; NITROFURAL; NITROFURAN DERIVATIVE; PENTAMIDINE; PENTAMIDINE DERIVATIVE; PENTAMIDINE ISETHIONATE; PROPAMIDINE ISETHIONATE; TRYPAN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ABSCESS; AFRICAN TRYPANOSOMIASIS; ANTIBIOTIC RESISTANCE; ANTIPROTOZOAL ACTIVITY; BRONCHOSPASM; CARDIOTOXICITY; CHAGAS DISEASE; CHEMOTHERAPY; CLINICAL TRIAL; COUGHING; DISEASE MODEL; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG FORMULATION; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TRANSPORT; ERYTHEMA; HUMAN; HYPOCALCEMIA; HYPOGLYCEMIA; HYPOTENSION; IN VITRO STUDY; IN VIVO STUDY; INSULIN DEPENDENT DIABETES MELLITUS; KIDNEY FAILURE; LEISHMANIASIS; LEUKOPENIA; LIVER DYSFUNCTION; MALARIA; MORBIDITY; MORTALITY; NEPHROTOXICITY; NONHUMAN; PANCREAS DISEASE; PARASITOSIS; PNEUMOCYSTOSIS; REVIEW; TASTE DISORDER; THROMBOCYTOPENIA; TRYPANOSOMA;

ANIMALS; ANTIPARASITIC AGENTS; DRUGS, INVESTIGATIONAL; HUMANS; PARASITIC DISEASES; PENTAMIDINE;

EID: 23644434124     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.14.8.957     Document Type: Review

References (167)

1. CUSHION MT, WALZER PD, COLLINS MS et al.: Highly active anti-Pneumocystis carinii compounds in a library of novel piperazine-linked bisbenzamidines and related compounds. Antimicrob. Agents Chemother. (2004) 48:4209-4216.
2. MEHTA A, SHAHA C: Apoptotic death in Leishmania donovani promastigotes in response to respiratory chain inhibition: complex II inhibition results in increased pentamidine cytotoxicity. J. Biol. Chem. (2004) 279(12):11798-11813.
3. DE SOUZA EM, LANSIAUX A, BAILLY C et al.: Phenyl substitution of furamidine markedly potentiates its antiparasitic activity against Trypanosoma cruzi and Leishmania (l) amazonensis. Biochem. Pharmacol. (2004) 68:593-600.
4. DEETZ TR, SAWYER MH, BILLMAN G, SCHUSTER FL, VISVESVARA GS: Successful treatment of Balamuthia amoebic encephalitis: presentation of 2 cases. Clin. Infect. Dis. (2003) 37(10):1304-1312.
5. LIONAKIS MS, LEWIS RE, SAMONIS G, KONTOYIANNIS DP: Pentamidine is active in vitro against Fusarium species. Antimicrob. Agents Chemother. (2003) 47(10):3252-3259.
6. MACHARIA JC, BOURDICHON AJ, GICHERU MM: Efficacy of Trypan: a diminazene-based drug as antileishmanial agent. Acta Trop. (2004) 92:267-272.
7. BRYCESON AD, CHULAY JD, MUGAMBI M et al.: Visceral leishmaniasis unresponsive to antimonial drugs. II. Response to high dosage sodium stibogluconate or prolonged treatment with pentamidine. Trans. R. Soc. Trop. Med. Hyg. (1985) 79:705-714.
8. TIDWELL RR, BOYKIN DW: Minor groove binders as antimicrobial agents. In: Small molecule DNA and RNA binder: synthesis to nucleic acid complexes. Wiley-VCH, New York, USA (2003):416-460.
9. LINDSAY DS, BLAGBURN BL, HALL JE, TIDWELL RR: Activity of pentamidine and pentamidine analogs against Toxoplasma gondii in cell cultures. Antimicrob. Agents Chemother. (1991) 35:1914-1916.
10. DENISE H, BARRETT MP: Uptake and mode of action of drugs used against sleeping sickness. Biochem. Pharmacol. (2001) 61:1-5.
11. APTED FI: Present status of chemotherapy and chemopropylaxis of human trypanosomiasis in the Eastern hemisphere. Pharmacol. Ther. (1980) 11(2):391-413.
12. JUNG S, SCHELPER RL, VISVESVARA GS, CHANG HT: Balamuthia mandrillaris meningoencephalitis in an immunocomperent patient: an unusual clinical course and a favorable outcome. Arch. Pathol. Lab. Med. (2004) 128(4):466-468.
13. PEREZ-SANTONJA JJ, KILVINGTON S, HUGHES R, TUFAIL A, MATHESON M, DART JK: Persistently culture positive acanthamoeba keratitis: in vivo resistance and in vitro sensitivity. Ophthalmology (2003) 110(8):1593-600.
14. PERRINE D, CHENU JP, GEORGES P, LANCELOT JC, SATURNINO C, ROBBA M: Amoebicidal efficiencies of various diamidines against two strains of Acanthamoeba polyphaga. Antimicrob. Agents Chemother. (1995) 39(2):339-342.
15. RUEBUSH TK, CONTACOS PG, STECK FA: Chemotherapy of Babesia microti infections in Mongolian Jirds. Antimicrob. Agents Chemother. (1980) 18(2):289-291.
16. CALONGE MM, BAYOUMI AE, CUBRIA JC, BALANA-FOUCE R, ORDONEZ D: Effects of cationic diamidines on polyamine metabolism in the trypanosomatid Crithidia fasciculata. Life Sci. (1996) 59:PL191-PL197.
17. BLAGBURN BL, SUNDERMANN CA, LINDSAY DS, HALL JE, TIDWELL RR: Inhibition of Cryptosporidium parvum in neonatal Hsd:(ICR)BR Swiss mice by polyether ionophores and aromatic amidines. Antimicrob. Agents Chemother. (1991) 35:1520-1523.
18. BELL CA, DYKSTRA CC, NAIMAN NA, CORY M, FAIRLEY TA, TIDWELL RR: Structure-activity studies of dicationically substituted bis-benzimidazoles against Giardia lamblia: correlation of antigiardial activity with DNA binding affinity and giardial topoisomerase II inhibition. Antimicrob. Agents Chemother. (1993) 37(12):2668-2673.
19. LANTERI CA, TRUMPOWER BL, TIDWELL RR, MESHNICK SR: DB75, a novel trypanocidal agent, disrupts mitochondrial function in Saccharomyces cerevisiae. Antimicrob. Agents Chemother. (2004) 48:3968-3974.
20. MILETTI KE, LEIBOWITZ MJ: Pentamidine inhibition of group I intron splicing in Candida albicans correlates with growth inhibition. Antimicrob. Agents Chemother. (2000) 44(4):958-966.
21. DEL POETA M, SCHELL WA, DYKSTRA CC et al.: Structure in vitro activity relationships of pentamidine analogues and dication-substituted bis-benzimidazoles as new antifungal agents. Antimicrob. Agents Chemother. (1998) 42(10):2495-2502.
22. BARCHIESI F, DEL POETA M, MORBIDUCCI V, ANCARANI F, SCALISE G: Effect of pentamidine on the growth of Cryptococcus neoformans. J. Antimicrob. Chemother. (1994) 33(6):1229-1232.
23. AFELTRA J, MEIS JF, VITALE RG, MOUTON JW, VERWEIJ PE: In vitro activities of pentamidine pyrimethamine trimethoprim and sulfonamides against Aspergillus species. Antimicrob. Agents Chemother. (2002) 46(6):2029-2031.
24. AFELTRA J, DANNAOUI E, MEIS JFGM, RODRIGUEZ-TUDELA JL, VERWEIJ PE, NETWORK E: In vitro Synergistic Interaction between Amphotericin B and Pentamidine against Scedosporium prolificans. Antimicrob. Agents Chemother. (2002) 46:3323-26.
25. CROWELL AL, STEPHENS CE, KUMAR A, BOYKIN DW, SECOR WE: Activities of dicarionic compounds against Trichomonas vaginalis. Antimicrob. Agents Chemother. (2004) 48(9):3602-3605.
26. BOYKIN DW, KUMAR A, SPYCHALA J et al.: Dicarionic diaryl furans as anti-Pneumocystis carinii agents. J. Med. Chem. (1995) 38:912-916.
27. VASCONCELLES MJ, BERNARDO MV, KING C, WELLER FA, ANTIN JH: Aerosolized pentamidine as pneumocystis prophylaxis after bone marrow transplantation is inferior to other regimens and is associated with decreased survival and an increased risk of other infections. Biol. Blood Marrow Transplant. (2000) 6(1):35-43.
28. PUCKOWSKA A, BIELAWSKI K, BIELAWSKA A, MIDURA-NOWACZEK K: Aromatic analogues of DNA minor groove binders-synthesis and biological evaluation. Eur. J. Med. Chem. (2004) 39(1):99-105.
29. LANSIAUX A, TANIOUS F, MISHAL Z et al.: Distribution of furamidine analogues in tumor cells: targeting of the nucleus or mitochondria depending on the amidine substitution. Cancer Res. (2002) 62:7219-7229.
30. BAILLY C, DASSONNEVILLE L, CARRASCO C et al.: Relationships between topoisomerase II inhibition, sequence-specificity and DNA binding mode of dicationic diphenylfuran derivatives. AntiCancer Drug Des. (1999) 14(1):47-60.
31. NEIDLE S, KELLAND LR, TRENT JO et al.: Cytotoxicity of bis-(phenylamidinium) furan alkyl derivatives in human tumor cell line: relation to DNA minor groove binding. Bioorg. Med. Chem. Lett. (1997) 7:1403-1406.
32. SCHOENBACH, EB, GREENSPAN EM: The pharmacology, mode of action and therapeutic potentialities of stilbamidine, pentamidine, propamidine and other aromatic diamidines - a review. Medicine (Baltimore) (1948) 27:327-377.
33. WILSON WD, NGUYEN B, TANIOUS FA et al.: Dications that target the DNA minor groove: compound design and preparation, DNA interactions, cellular distribution and biological activity. Curr. Med. Chem. (2005) 5:380-408.
34. OBAJI J, LEE-PACK LR, GUTIERREZ C, CHAN CK: The pulmonary effects of long-term exposure to aerosol pentamidine: a 5-year surveillance study in HIV-infected patients. Chest (2003) 123(6):1983-1987.
35. COYLE P, CARR AD, DEPCZYNSKI BB, CHISHOLM DJ: Diabetes mellitus associated with pentamidine use in HIV-infected patients. Med. J. Aust. (1996) 165(10):587-588.
36. PELUCIO MT, ROTHENHAUS T, SMITH M, WARD DJ: Fatal pancreatitis as a complication of therapy for HIV infection. J. Emerg. Med. (1995) 13(5):633-637.
37. GLIKSON M, DRESNER-FEIGIN R, POLLACK A, WOLF D, GALUN E, KASPA RT: Pentamidine-induced cardiotoxicity. Isr. J. Med. Sci. (1990) 26(10):588-589.
38. KURYSHEV YA, FICKER E, WANG L et al.: Pentamidine-induced long QT syndrome and block of hERG trafficking. J. Pharm. Exp. Therap. (2005) 312(1):316-323.
39. SEAL D, HAY J, KIRKNESS C et al.: Successful medical therapy of Acanthamoeba keratitis with topical chlorhexidine and propamidine. Eye (1996) 10:413-421.
40. DUGUID IG, DART JK, MORLET N et al.: Outcome of Acanthamoeba keratitis treated with polyhexamethyl biguanide and propamidine. Ophthalmology (1997) 104(10):1587-1592.
41. ALIZADEH H, SILVANY RE, MEYER DR, DOUGHERTY JM, McCULLEY JP: In vitro amoebicidal activity of propamidine and pentamidine isethionate against Acanthamoeba species and toxicity to corneal tissues. Cornea (1997) 16(1):94-100.
42. BRASSEUR G, FAVENNEC L, PERRINE D, CHENU JP, BRASSEUR P: Successful treatment of Acanthamoeba keratitis by hexamidine. Cornea (1994) 13:459-462.
43. CLEMENT B, IMMEL M, TERLINDEN R, WINGEN FJ: Reduction of amidoxime derivatives to pentamidine in vivo. Arch. Pharm. (Weinheim) (1992) 325(1):61-62.
44. LEON W, BRUN R, KRASSNER SM: Effect of berenil on growth, mitochondrial DNA and respiration of Leishmania tarentolae promastigotes. J. Protozool. (1977) 24(3):444-448.
45. MUKHOPADHYAY R, MADHUBALA R: Anti-leishmanial activity of berenil and methylglyoxal bis-(guanylhydrazone) and its correlation with S-adenosylmethionine decarboxylase and polyamines. Int. J. Biochem. Cell Biol. (1995) 27(1):55-59.
46. LYNEN L, VAN DAMME W: Local application of diminazene aceturate: an effective treatment for cutaneous leishmaniasis? Ann. Soc. Belg. Med. Trop. (1992) 72(1):13-19.
47. VAN NIEUWENHOVE S: Present strategies in the treatment of human African trypanosomiasis. In: Progress in human African trypanosomiasis, sleeping sickness. Dumas M, Bouteille B, Buguet A (Eds), Springer-Verlag, Paris, France (1999):253-280.
48. ATOUGUIA J, COSTA J: Therapy of human African trypanosomiasis: current situation. Mem. Inst. Oswaldo Cruz (1999) 94(2):221-224.
49. EGBE-NWIYI TN, IGBOKWE IO, ONYEYILI PA: The pathogenicity of diminazene aceturate-resistant Trypanosoma brucei in rats after treatment with the drug. J. Comp. Pathol. (2003) 128(2-3):188-191.
50. BOYKIN DW, KUMAR A, BENDER BK, HALL JE, TIDWELL RR: Anti-pneumocystis activity of bis-amidoximes and bis-O-alkylamidoximes. Bioorg. Med. Chem. Let. (1996) 6:3017-3020.
51. RAHMATHULLAH SM, HALL JE, BRENDER BC, McCURDY DR, TIDWELL RR, BOYKIN DW: Prodrugs for Amidines: Synthesis and Anti-Pneumocystis carinii Activity of Carbamates of 2,5-bis-[4-amidinophenyl]furan. J. Med. Chem. (1999) 42: 3994-4000.
52. BOUTEILLE B, OUKEM O, BISSER S, DUMAS M: Treatment perspectives for human African trypanosomiasis. Fundam. Clin. Pharmacol (2003) 17:171-181.
53. ISMAIL MA, BRUN R, EASTERBROOK JD, TANIOUS FA, WILSON WD, BOYKIN DW: Synthesis and antiprotozoal activity of aza-analogues of furamidine. J. Med. Chem. (2003) 46(22):4761-4769.
54. ANSEDE JH, ANBAZHAGAN M, BRUN R, EASTERBROOK JD, HALL JE, BOYKIN DW: O-alkoxyamidine prodrugs of furamidine: in vitro transport and microsomal metabolism as indicators of in vivo efficacy in a mouse model of Trypanosoma brucei rhodesiense infection. J. Med. Chem. (2004) 47(17):4335-4338.
55. ISMAIL MA, BRUN R, WENZLER T, TANIOUS FA, WILSON WD, BOYKIN DW: Novel dicationic imidazo[1,2-a]pyridines and 5,6,7,8-tetrahydro-imidazo[1,2-a]pyridines as antiprotozoal agents. J. Med. Chem. (2004) 47(14):3658-3664.
56. BRUN R, BUHLER Y, SANDMEIER U et al.: In vitro trypanocidal activities of new S-adenosylmethionine decarboxylase inhibitors. Antimicrob. Agents Chemother. (1996) 40:1442-1447.
57. BACCHI CJ, BRUN R, CROFT SL, ALICEA K, BUHLER Y: In vivo trypanocidal activities of new S-adenosylmethionine decarboxylase inhibitors. Antimicrob. Agents Chemother. (1996) 40(6):1448-1453.
58. BRUN R, BURRI C, GICHUKI CW: The story of CGP-40215: studies on its efficacy and pharmacokinetics in African green monkey infected with Trypanosoma brucei rhodesiense. Trop. Med. Int. Health. (2001) 6(5):362-368.
59. WILSON WD, TANIOUS FA, DING D et al.: Nucleic acid interactions of unfused aromatic cations: evaluation of proposed minor-groove, major-groove and intercalation binding modes. J. Am. Chem. Soc. (1998) 120:10310-10321.
60. BOYKIN DW, KUMAR A, XIAO G et al.: 2,5-bis[4-(N-alkylamidino) phenyl]furans as anti-Pneumocystis carinii agents. J. Med. Chem. (1998) 41:124-129.
61. NGUYEN B, LEE MP, HAMELBERG D et al.: Strong binding in the DNA minor groove by an aromatic diamidine with a shape that does not match the curvature of the groove. J. Am. Chem. Soc. (2002) 124(46):13680-13681.
62. NGUYEN B, HAMELBERGE D, BAILLY C et al.: Caracterization of a novel DNA minor-groove complex. Biophys. J. (2004) 86:1028-1041.
63. MESA-VALLE CM, RODRIGUES-CABEZAS MN, MORALEDA-LINDEZ V, CRACIUNESCU D, SANCHEZ-MORENO M, OSUNA A: In vitro and in vivo activity of two Pt (IV) salts against Leishmania donovani. Int. J. Exp. Clin. Pharmcol (1998) 57(3):160-172.
64. FUSAI T, BOULARD Y, DURAND R et al.: Ultrastructural changes in parasites induced by nanoparticle-bound pentamidine in a Leishmania major/mouse model. Parasite (1997) 4(2):133-139.
65. CROFT SL, BRAZIL RP: Effect of pentamidine isethionate on the ultrastructure and morphology of Leishmania mexicana amazonensis in vitro. Ann. Trop. Med. Parasitol. (1982) 76:37-43.
66. LANGRETH SG, BERMAN JD, RIORDAN GP, LEE LS: Fine-structural alterations in Leishmania tropica within human macrophages exposed to antileishmanial drugs in vitro. J. Protozool. (1983) 30(3):555-561.
67. HENTZER B, KOBAYASI T: The ultrastructural changes of Leishmania tropica after treatment with pentamidine. Ann. Trop. Med. Parasitol. (1977) 71(2):157-166.
68. DELAIN E, BRACK C, RIOU G, FESTY B: Ultrastructural alterations of Trypanosoma cruzi kinetoplast induced by the interaction of a trypanocidal drug (hydroxystilbamidine) with the kinetoplast DNA. J. Ultrastruct. Res. (1971) 37(1):200-218.
69. BASSELIN M, BADET-DENISOT MA, ROBERT-GERO M: Modification of kinetoplast DNA minicircle composition in pentamidine-resistant Leishmania. Acta Trop. (1998) 70:43-61.
70. JOHNSON R, CUBRIA JC, REGUERA RM, BALANA-FOUCE R, ORDONEZ D: Interaction of cationic diamidines with Leishmania infantum DNA. Biol. Chem. (1998) 379(7):925-930.
71. MAYENCE A, EYNDE JJV, LE COUR JL, WALKER LA, TEKWANI BL, HUANG TL: Piperazine-linked bisbenzamidines: a novel class of antileishmanial agents. (2004) 39:547-553.
72. MacADAM RF, WILLIAMSON J: Drug effects on the fine structure of Trypanosoma rhodesiense: diamidines. Trans. R. Soc. Trop. Med. Hyg. (1972) 66(6):897-904.
73. AGBE A, YIELDING KL: Kinetoplasts play an important role in the drug responses of Trypanosoma brucei. J. Parasitol. (1995) 81(6):968-973.
74. MORENO SN: Pentamidine is an uncoupler of oxidative phosphorylation in rat liver mitochondria. Arch. Biochem. Biophys. (1996) 326(1):15-20.
75. TERADA H, NAGAMUNE H, MORIKAWA N, IKUNO M: Uncoupling of oxidative phosphorylation by divalent cationic cyanine dye. Participation of phosphate transporter. Biochim. Biophys. Acta. (1985) 807(2):168-176.
76. 2+, pentamidine and WR-6026 on mitochondrial membrane potential in situ. Biochem. J (1992) 284(2):463-467.
77. SHAPIRO TA, ENGLUND PT: Selective cleavage of kinetoplast DNA minicircles promoted by antitrypanosomal drugs. Proc. Natl. Acad. Sci. USA (1990) 87(3):950-954.
78. GENESTRA M, ECHEVARRIA A, CYSNE-FINKELSTEIN L, LEON LL: Protein kinase A of Leishmania amazonensis as a potential target for methoxy-amidine. Arzneimittelforschung (2001) 51(11):920-923.
79. MORTY RE, TROEBERG L, PIKE RN et al.: A trypanosome oligopeptidase as a target for the trypanocidal agents pentamidine, diminazene and suramin. FEBS Lett. (1998) 433(3):251-256.
80. BASSELIN M, BADET-DENISOT MA, LAWRENCE F, ROBERT-GERO M: Effect of pentamidine on polyamine level and biosynthesis in wild-type, pentamidine-treated, and pentamidine-resistant Leishmania. Exp. Parasitol. (1997) 85:274-282.
81. DYKSTRA CC, TIDWELL RR: Inhibition of topoisomerases from Pneumocystis carinii by aromatic dicationic molecules. J. Protozool. (1991) 38(6):785-815.
82. SANDS M, KRON MA, BROWN RB: Pentamidine: a review. Rev. Infect. Dis. (1985) 7(5):625-634.
83. MARCUS SL, KOPELMAN R, KOLL B, BACCHI CJ: Effects of exogenous polyamine and trypanocides on the DNA polymerase activities from Trypanosoma brucei brucei, mouse thymus and murine leukemia virus. Mol. Biochem. Parasitol. (1982) 5(4):231-243.
84. DYKSTRA CC, McCLERNON DR, ELWELL LP, TIDWELL RR: Selective inhibition of topoisomerases from Pneumocystis carinii compared with that of topoisomerases from mammalian cells. Antimicrob. Agents Chemother. (1994) 38(9):1890-1898.
85. BRAY PG, BARRETT MP, WARD SA, DE KONING HP: Pentamidine uptake and resistance in pathogenic protozoa: past, present and future. Trends Parasitol. (2003) 19:232-239.
86. MASER P, LUSCHER A, KAMINSKY R: Drug transport and drug resistance in African trypanosomes. Drug Resist Updat. (2003) 6(5):281-290.
87. BARRETT MP, FAIRLAMB AH: The biochemical basis of arsenical-diamidine crossresistance in African trypanosomes. Parasitol Today. (1999) 15(4):136-140.
88. MASER P, SUTTERLIN C, KRALLI A, KAMINSKY R: A nucleoside transporter from Trypanosoma brucei involved in drug resistance. Science (1999) 285(5425):242-244.
89. BASSELIN M, LAWRENCE F, ROBERT-GERO M: Pentamidine uptake in Leishmania donovani and Leishmania amazonensis promastigotes and axenic amastigotes. Biochem. J. (1996) 315:631-634.
90. CARTER NS, BERGER BJ, FAIRLAMB AH: Uptake of diamidine drugs by the P2 nucleoside transporter in melarsen-sensitive and -resistant Trypanosoma brucei brucei. J. Biol. Chem. (1995) 270(47):28153-28157.
91. BERGER BJ, CARTER NS, FAIRLAMB AH: Characterization of pentamidine-resistant Trypanosoma brucei brucei. Mol. Biochem. Parasitol. (1995) 69(2):289-298.
92. DAMPER D, PATTON CL: Pentamidine transport in Trypanosoma brucei-kinetics and specificity. Biochem. Pharmacol (1976) 25(3):271-276.
93. CARTER NS, BARRETT MP, DE KONING HP: A drug resistance determinant in Trypanosoma brucei. Trends Microbiol. (1999) 7(12):469-471.
94. NOK AJ: Arsenicals (melarsoprol), pentamidine and suramin in the treatment of human African trypanosomiasis. Parasitol. Res. (2003) 90(1):71-79.
95. MATOVU E, STEWART ML, GEISER F et al.: Mechanisms of arsenical and diamidine uptake and resistance in Trypanosoma brucei. Eukaryot. Cell (2003) 2(5):1003-1008.
96. DE KONING HP: Uptake of pentamidine in Trypanosoma brucei brucei is mediated by three distinct transporters: implications for cross-resistance with arsenicals. Mol. Pharmacol. (2001) 59(3):586-592.
97. FAIRLAMB AH, CARTER NS, CUNNINGHAM M, SMITH K: Characterisation of melarsen-resistant Trypanosoma brucei brucei with respect to cross-resistance to other drugs and trypanothione metabolism. Mol. Biochem. Parasitol. (1992) 53(1-2):213-222.
98. BASSELIN M, DENISE H, COOMBS GH, BARRETT MP: Resistence to Pentamidine in Leishmania mexicana Involves Exclusion of the Drug from the Mitochondrion. Antimicrob. Agents Chem. (2002) 46(12):3731-3738.
99. STEAD AMW, BRAY PG, EDWARDS IG et al.: Diamidine compounds: novel antimalarials with two levels of selectivity against Plasmodium falciparum. Mol. Pharmacol. (2001) 59:1298-1306.
100. BIAGINI GA, PASINI EM, HUGHES R et al. Characterization of the choline carrier of Plasmodium falciparum: a route for the selective delivery of novel antimalarial drugs. Blood (2004) 104:3372-3377.
101. CUNNINGHAM AC: Parasitic adaptive mechanisms in infection by Leishmania. Exp. Mol. Pathol. (2002) 72(2):132-141.
102. WHO: The world health report. Genova. World Health Organization (2002).
103. YEPEZ JY, DAGER JVS: Quimioterapia de la leishmaniasis cutánea localizada. Bol. de Malariol. Y Salud Amb. (2003) 1:9-20.
104. TEMPORAL RM, CYSNE-FINKELSTEIN L, ECHEVARRIA A et al.: Effects of amidine derivatives on parasite-macrophage interaction and evaluation of toxicity. Arzneimittelforschung (2002) 52(6):489-493.
105. COOMBS GH, HART DT, CAPALDO J: Proteinase inhibitors as antileishmanial agents. Trans. R. Soc. Trop. Med. Hyg. (1982) 76(5):660-663.
106. OUELLETTE M, DRUMMELSMITH J, PAPADOPOULOU B: Leishmaniasis: drugs in the clinic, resistance and new developments. Drug Resist. Updat. (2004) 7(4-5):257-266.
107. BERMAN JD: Human leishmaniasis: clinical, diagnostic, and chemotherapeutic developments in the last 10 years. Clin. Infect. Dis. (1997) 24:684-703.
108. AMATO VS, DE PAULA JG, IMAMURA R et al.: Treatment of american cutaneous leishmaniasis, with lesions in the mucosa, using pentamidine isethionate. Rev. Soc. Bras. Med. Trop. (1996) 29(5):477-481.
109. BECKER I, VOLKOW P, VELASCO-CASTREJON O et al.: The efficacy of pentamidine combined with allopurinol and immunotherapy for the treatment of patients with diffuse cutaneous leishmaniasis. Parasitol. Res. (1999) 85(3):165-170.
110. MBONGO N, LOISEAU PM, LAWRENCE F, BORIES C, CRACIUNESCU DG, ROBERT GERO M: In vitro sensitivity of Leishmania donovani to organometallic derivatives of pentamidine. Parasitol Res. (1997) 83(5):515-517.
111. MBONGO N, LOISEAU PM, CRACIUNESCU DG, ROBERT-GERO M: Synergistic effect of Ir-(COT)-pentamidine alizarin red and pentamidine, amphotericin B, and paromomycin on Leishmania donovani. Acta Trop. (1998) 70(2):239-245.
112. DURAND R, PAUL M, RIVOLLET D et al.: Activity of pentamidine-loaded poly (D,L-lactide) nanoparticles against Leishmania infantum in a murine model. Parasite (1997) 4(4):331-336.
113. DENIAU M, DURAND R, BORIES C et al.: In vitro study of leishmanicidal agents with drug carriers. Ann. Parasitol. Hum. Comp. (1993) 68(1):34-37.
114. KAYSER O, MASIHI KN, KIDERLEN AF: Natural products and synthetic compounds as immunomodulators. Expert. Rev. Anti. Infect. Ther. (2003) 1(2):319-335.
115. BANERJEE G, NANDI G, MAHATO SB, PAKRASHI A, BASU MK: Drug delivery system: targeting of pentamidines to specific sites using sugar grafted liposomes. J. Antimicrob. Chemother. (1996) 38(1):145-150.
116. BRENDLE JJ, OUTLAW A, KUMAR A et al.: Antileishmanial activities of several classes of aromatic dications. Antimicrob. Agents Chemother. (2002) 46:797-807.
117. STEPHENS CE, BRUN R, SALEM MM et al.: The activity of diguanidino and 'reversed' diamidino 2,5-diarylfurans versus Trypanosoma cruzi and Leishmania donovani. Bioorg. Med. Chem. Lett. (2003) 13(12):2065-2069.
118. DO CAMPO R, MORENO SN: Current chemotherapy of human African trypanosomiasis. Parasitol. Res. (2003) 90(1):10-13.
119. RASEROKA BH, ORMEROD WE: Protection of the sleeping sickness trypanosome from chemotherapy by different parts of the brain. East Afr. Med. J. (1985) 62(7):452-458.
120. DOUA F, MIEZAN TW, SANON SINGARO JR, BOA YAPO F, BALTZ T: The efficacy of pentamidine in the treatment of early-late stage Trypanosoma brucei gambiense trypanosomiasis. Am. J. Trop. Med. Hyg. (1996) 55(6):586-588.
121. MIEZAN TW, BRONNER U, DOUA F, CATTAND P, ROMBO L: Long-term exposure of Trypanosoma brucei gambiense to pentamidine in vitro. Trans. R. Soc. Trop. Med. Hyg. (1994) 88(3):332-333.
122. LEGROS D, FOURNIER C, GASTELLU EM, MAISO F, SZUMILIN E: Therapeutic failure of melarsoprol among patients treated for late stage T. b. gambiense human African trypanosomiasis in Uganda Bull. Soc. Pathol. Exot. (1999) 92(3):171-172.
123. DONKOR IO, HUANG TL, TAO B et al.: Trypanocidal activity of conformationally restricted pentamidine congeners. J. Med. Chem. (2003) 46(6):1041-1048.
124. DARDONVILLE C, BRUN R: Bisguanidine, bi(2-aminoimidazoline), and polyamine derivatives as potent and selective chemotherapeutic agents against Trypanosoma brucei rhodesiense. J. Med. Chem. (2004) 47:2296-2307.
125. BURRI C, YERAMIAN PD, ALLEN JL et al.: Efficacy and safety of DB289, a new oral drug for treatment of first stage sleeping sickness: an open-label, non-controlled Phase II Trial. Presented at the 52nd Annual Meeting of the American Society of Tropical Medicine and Hygiene. Philadelphia, PA, USA (2003):3-7.
126. STURK LM, BROCK JL, BAGNELL CR, HALL JE, TIDWELL RR: Distribution and quantitation of the anti-trypanosomal diamidine 2,5-bis(4-amidinophenyl) furan (DB75) and its N-methoxy prodrug DB289 in murine brain tissue. Acta Trop. (2004) 91:131-143.
127. HIRST SI, STAPLEY LA: Parasitology: the dawn of a new millennium. Parasitol. Today (2000) 16(1):1-3.
128. COURA RJ, DE CASTRO SL: A critical review on Chagas' disease chemotherapy. Mem. Inst. Oswaldo Cruz (2002) 97:3-24.
129. URBINA JA: Chemotherapy of Chagas disease. Curr Pharm Des. (2002) 8:287-295.
130. ROWLAND EC, MOORE-LAI D, SEED JR, STEPHENS CE, BOYKIN DW: Inhibition of in vitro intracellular growth of Trypanosoma cruzi by dicationic compounds. J. Parasitol. (2003) 89(5):1078-1080.
131. BORGES MN, MESSEDER JC, FIGUEROA-VILLAR JD: Synthesis, anti-Trypanosoma cruzi activity and micelle interaction studies of bisguanylhydrazones analogous to pentamidine. Eur. J. Med. Chem. (2004) 39:925-929.
132. PETERSEN E: Malaria chemoprophylaxis: when should we use it and what are the options? Expert Rev. Anti-Infect. Ther. (2004) 2(1):119-132.
133. HEISCHKEIL R: Effectiveness of trypanocides berenil and pentamidine in rodent malaria (Plasmodium vinckei). Z. Tropenmed. Parasitol. (1971) 22(3):243-249.
134. DAS B, GUPTA R, MADHUBALA R: Combined action of inhibitors of S-adenosylmethionine decarboxylase with an antimalarial drug, chloroquine, on Plasmodium falciparum. J. Eukaryot. Microbiol. (1997) 44:12-17.
135. DAS BP, BOYKIN DW: Synthesis and antiprotozoal activity of 2,5-bis(4-guanyl-phenyl) thiophenes and pyrroles. J. Med. Chem. (1977) 20:1219-1222.
136. DAS BP, WALLACE RA, BOYKIN DW: Synthesis and Antitrypanosomal Activity of Some Bis(4-Guanylphenyl) Five and Six Membered Ring Heterocyclics. J. Med. Chem. (1980) 23:578-581.
137. BELL CA, HALL JE, KYLE DE et al.: Structure-activity relationships of analogs of pentamidine against Plasmodium falciparum and Leishmania mexicana amazonensis. Antimicrob. Agents Chemother. (1990) 34(7):1381-1386.
138. MAYENCE A, VANDEN EYNDE JJ, KROGSTAD FM, KROGSTAD DJ, CUSHION MT, HUANG TL: Parallel solution-phase synthesis of conformationally restricted congeners of pentamidine and evaluation of their antiplasmodial activities. J. Med. Chem. (2004) 47(10):2700-2705.
139. YERAMIAN P, KRUDSOOD S, CHALERMRUT K et al.: Efficacy of DB289 in acute uncomplicated P. falciparum/P. vivax malaria. Presented at the 52nd Annual Meeting of the American Society of Tropical Medicine and Hygiene, Philadelphia, PA, USA (2003):3-7.
140. WAZIR JF, ANSARI NA: Pneumocystis carinii infection. Update and review. Arch. Pathol. Lab. Med. (2004) 128(9):1023-1027.
141. FISHMAN JA: Treatment of infection due to Pneumocystis carinii. Antimicrob. Agents Chemother. (1998) 42(6):1309-1314.
142. YOUNG FE, NIGHTINGALE SL, COOPER EC, TRAPNELL CB: Aerosolized pentamidine. Approved for HIV-infected individuals at high risk for Pneumocystis carinii pneumonia. Arch. Intern. Med. (1989) 149(11):2412-2413.
143. HAND IL, WIZNIA A, PORRICOLA M: Administration of aerosolized pentamidine to HIV-infected infants. Ann. NY Acad Sci. (1993) 29(693):300-301.
144. PEARSON RD, HEWLETT EL: Pentamidine for the treatment of Pneumocystis carinii pneumonia and other protozoal diseases. Ann. Intern. Med. (1985) 103(5):782-786.
145. CHAN M, LEE-PACK LR, FAVELL K, CHAN CK: Acute pulmonary effects of three nebulizers for administering aerosol pentamidine: comparison of Parineb to Fisoneb and Respirgard II. J. Aerosol Med. (1996) 9(4):521-526.
146. LU CP, WU HP, CHUANG LM, LIN BJ, CHUANG CY, TAI TY: Pentamidine-induced hyperglycemia and ketosis in acquired immunodeficiency syndrome. Pancreas (1995) 11(3):315-316.
147. JULES-ELYSEE KM, STOVER DE, ZAMAN MB, BERNARD EM, WHITE DA: Aerosolized pentamidine: effect on diagnosis and presentation of Pneumocystis carinii pneumonia. Ann. Intern. Med. (1990) 112(10):750-757.
148. LEVINE SJ, KENNEDY D, SHELHAMER JH et al.: Diagnosis of Pneumocystis carinii pneumonia by multiple lobe, site-directed bronchoalveolar lavage with immunofluorescent monoclonal antibody staining in human immunodeficiency virus-infected patients receiving aerosolized pentamidine chemoprophylaxis. Am. Rev. Respir. Dis. (1992) 146(4):838-843.
149. FAHY JV, CHIN DP, SCHNAPP LM et al.: Effect of aerosolized pentamidine prophylaxis on the clinical severity and diagnosis of Pneumocystis carinii pneumonia. Am. Rev. Respir. Dis. (1992) 146(4):844-848.
150. READ CA, CERRONE F, BUSSENIERS AE, WALDHORN RE, LAVELLE JP, PIERCE PF: Differential lobe lavage for diagnosis of acute Pneumocystis carinii pneumonia in patients receiving prophylactic aerosolized pentamidine therapy. Chest (1993) 103(5):1520-1523.
151. EWIG S, SCHAFER H, ROCKSTROH JK, PICKENHAIN A, LUDERITZ B: Effect of long-term primary aerosolized pentamidine prophylaxis on breakthrough Pneumocystis carinii pneumonia. Eur. Respir. J. (1996) 9(5):1006-1012.
152. NOLAN A, LAMEY PJ, MacFARLANE TW, AITCHISON TC, SHAW J, SIREL JY: The effect of nebulised pentamidine on the concentration of intraoral Candida albicans in HIV-infected patients. J. Med. Microbiol. (1994) 41(2):95-97.
153. TIDWELL RR, JONES SK, GERATZ JD et al.: Development of pentamidine analogues as new agents for the treatment of Pneumocystis carinii pneumonia. Ann. NY Acad. Sci. (1990) 616:421-441.
154. JONES SK, HALL JE, ALLEN MA et al.: Novel pentamidine analogs in the treatment of experimental Pneumocystis carinii pneumonia. Antimicrob. Agents Chemother. (1990) 34(6):1026-1030.
155. TIDWELL RR, JONES, SK, DYKSTRA CC, GORTON L, HALL JE: Treatment of Experimental Pneumocystis carinii pneumonia with 1,3-Di(4-Imidazolino-2-ethoxyphenoxy) Propane Lactate. J. Protozool. (1991) 38:148S-150S.
156. DONKOR IO, ASSEFA H, RATTENDI D et al.: Trypanocidal activity of dicationic compounds related to pentamidine. Eur. J. Med. Chem. (2001) 36(6):531-538.
157. TIDWELL RR, JONES SK, NAIMAN NA et al.: Activity of cationically substituted bisbenzimidazoles against experimental Pneumocystis carinii pneumonia. Antimicrob. Agents Chemother (1993) 37:1713-1716.
158. HUANG TL, ZHANG Q, WHITE AT et al.: Synthesis and Anti-Pneumocystis carinii Activity of Piperidine-linked Aromatic Diimidazolines. Bioorg. Med. Chem. Lett. (1996) 6:2087-2090.
159. HUANG TL, TAO B, QUARSHIE Y, QUEENER SF, DONKER IO: N,N′-Bis[4-(N-alkylamidino) phenyl]homopiperazines as Anti-Pneumocystis carinii Agents. Bioorg. Med. Chem. Lett. (2001) 11:2679-2681.
160. EYNDE JJV, MAYENCE A, HUANG TL et al.: Novel bisbenzamidines as potential drug candidates for the treatment of Pneumocystis carinii pneumonia. Bioorg. Med. Chem. Lett. (2004) 14:4545-4548.
161. HALL JE, KERRIGAN JE, RAMACHANDRAN K et al.: Anti-pneumocystis activities of aromatic diamidoxime prodrugs. Antimicrob. Agents Chemother. (1998) 42(3):666-674.
162. FRANCESCONI I, WILSON WD, TANIOUS FA et al.: 2,4-Diphenyl furan diamidines as novel anti-Pneumocystis carinii pneumonia agents. J. Med. Chem. (1999) 42(12):2260-2265.
163. YERAMIAN PD, CASTAGNINI LA, ALLEN JA, UMESH L, GOTUZZO E: Efficacy and safety of DB289, a new oral drug for treatment of Pneumocystis carinii pneumonia (PCP) in AIDS patients. Presented at the 43rd Annual InterscienceConference on Antimicrobial Agents in Chemotherapy Meeting. Chicago, IL, USA (2003):14-17.
164. DEL POETA M, SCHELL WA, DYKSTRA CC et al.: In vitro Antifungal Activity of a Series of Dication-Substituted Carbazoles, Furans and Benzimidazoles. Antimicrob. Agents Chemother. (1998) 42:2503-2510.
165. DONKOR IO, CLARK AM: In vitro antimicrobial activity of aromatic diamidines and diimidazoles related to pentamidine. Eur. J. Med. Chem. (1999) 34:639-643.
166. STEPHENS CE, TANIOUS F, KIM S et al.: Diguanidino and 'reversed' diamidino 2,5-diarylfurans as antimicrobial agents. J. Med. Chem. (2001) 44: 1741-1748.
167. CUSHION MT, CHEN F, KLOEPFER N: A cytotoxicity assay for evaluation of candidate anti-Pneumocystis carinii agents. Antimicrob. Agents Chemother. (1997) 41:379-384.