In vitro antifungal activities of a series of dication-substituted carbazoles, furans, and benzimidazoles

被引:73
作者
Del Poeta, M
Schell, WA
Dykstra, CC
Jones, SK
Tidwell, RR
Kumar, A
Boykin, DW
Perfect, JR
机构
[1] Duke Univ, Med Ctr, Div Infect Dis & Int Hlth, Dept Med, Durham, NC 27710 USA
[2] Auburn Univ, Dept Pathobiol, Auburn, AL 36849 USA
[3] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA
[4] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA
[5] Univ Ancona, Osped Umberto 1, Inst Infect Dis & Publ Hlth, I-60121 Ancona, Italy
关键词
D O I
10.1128/AAC.42.10.2503
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Aromatic dicationic compounds possess antimicrobial activity against a wide range of eucaryotic pathogens, and in the present study an examination of the structures-functions of a series of compounds against fungi was performed, Sixty-seven dicationic molecules were screened for their inhibitory and fungicidal activities against Candida albicans and Cryptococcus neoformans. The MICs of a large number of compounds were comparable to those of the standard antifungal drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory compounds in this series were found to have excellent fungicidal activities. The MIC of one of the most potent compounds against C, albicans was 0.39 mu g/ml, and it was the most potent compound against C, neoformans (MIC, less than or equal to 0.09 mu g/ml). Selected compounds were also found to be active against Aspergillus fumigatus, Fusarium solani, Candida species other than C, albicans, and fluconazole-resistant strains of C, albicans and C, neoformans. Since some of these compounds have been safely given to animals, these classes of molecules have the potential to be developed as antifungal agents.
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收藏
页码:2503 / 2510
页数:8
相关论文
共 32 条
[1]   STRUCTURE-ACTIVITY-RELATIONSHIPS OF PENTAMIDINE ANALOGS AGAINST GIARDIA-LAMBLIA AND CORRELATION OF ANTIGIARDIAL ACTIVITY WITH DNA-BINDING AFFINITY [J].
BELL, CA ;
CORY, M ;
FAIRLEY, TA ;
HALL, JE ;
TIDWELL, RR .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1991, 35 (06) :1099-1107
[2]  
BELL CA, 1993, ANTIMICROB AGENTS CH, V37, P2668, DOI 10.1128/AAC.37.12.2668
[3]  
BLAGBURN BL, UNPUB DICATIONIC FUR
[4]   DICATIONIC DIARYLFURANS AS ANTIPNEUMOCYSTIS CARINII AGENTS [J].
BOYKIN, DW ;
KUMAR, A ;
SPYCHALA, J ;
ZHOU, M ;
LOMBARDY, RJ ;
WILSON, WD ;
DYKSTRA, CC ;
JONES, SK ;
HALL, JE ;
TIDWELL, RR ;
LAUGHTON, C ;
NUNN, CM ;
NEIDLE, S .
JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (06) :912-916
[5]   2,5-bis[4-(N-alkylamidino)phenyl]furans as anti-Pneumocystis carinii agents [J].
Boykin, DW ;
Kumar, A ;
Xiao, G ;
Wilson, WD ;
Bender, BC ;
McCurdy, DR ;
Hall, JE ;
Tidwell, RR .
JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (01) :124-129
[6]   Anti-pneumocystis activity of bis-amidoximes and bis-O-alkylamidoximes prodrugs [J].
Boykin, DW ;
Kumar, A ;
Hall, JE ;
Bender, BC ;
Tidwell, RR .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (24) :3017-3020
[7]   CORRELATION OF IN-VITRO FLUCONAZOLE RESISTANCE OF CANDIDA ISOLATES IN RELATION TO THERAPY AND SYMPTOMS OF INDIVIDUALS SEROPOSITIVE FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 [J].
CAMERON, ML ;
SCHELL, WA ;
BRUCH, S ;
BARTLETT, JA ;
WASKIN, HA ;
PERFECT, JR .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1993, 37 (11) :2449-2453
[8]   Synthesis of mono-cationic and dicationic analogs of Hoechst 33258 [J].
Czarny, A ;
Wilson, WD ;
Boykin, DW .
JOURNAL OF HETEROCYCLIC CHEMISTRY, 1996, 33 (04) :1393-1397
[9]   ANALYSIS OF VAN-DER-WAALS AND ELECTROSTATIC CONTRIBUTIONS IN THE INTERACTIONS OF MINOR-GROOVE BINDING BENZIMIDAZOLES WITH DNA [J].
CZARNY, A ;
BOYKIN, DW ;
WOOD, AA ;
NUNN, CM ;
NEIDLE, S ;
ZHAO, M ;
WILSON, WD .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (16) :4716-4717
[10]   SYNTHESIS AND ANTIPROTOZOAL ACTIVITY OF 2,5-BIS(4-GUANYLPHENYL)FURANS [J].
DAS, BP ;
BOYKIN, DW .
JOURNAL OF MEDICINAL CHEMISTRY, 1977, 20 (04) :531-536