Trypanocide Diamidine mit vier Ringen in einem oder zwei Ringsystemen

Dann, Otto; Volz, Gerda; Demant, Ekke; Pfeifer, Wolfgang; Bergen, Gerhard; Fick, Helmut; Walkenhorst, Ekkehard

doi:10.1002/jlac.197319730708

Cited by 25 publications

(21 citation statements)

References 26 publications

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“…On substituting imidazolino groups for amidino groups, the antifungal activities of type A compounds generally diminished. This detrimental effect was less pronounced with the more active indoles (6, 4) than with the benzofurans (8,7) or benzothiophenes (17,13). Less disadvantageous was the replacement of the amidino groups by guanidino groups, as shown by 10 and 7 and by 19 and 13.…”

Section: Resultsmentioning

confidence: 98%

Antifungal and antibacterial activities of diarylamidine derivatives

Anné¹,

Clercq²,

Eyssen³

et al. 1980

Antimicrob Agents Chemother

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The antifungal and antibacterial properties of a series of 70 diarylamidine derivatives were evaluated. Several of these compounds exhibited considerable antimicrobial potency. A survey of the structure-activity relationship demonstrated that minor structural variations resulted in significant changes of antimicrobial activity. In general, the structural features required for antifungal activity coincided with those required for antibacterial activity. Both the antifungal and the antibacterial properties of the diarylamidines depended on the presence and the positions, of both amidino groups, on the nature of the central bridge connecting the two aryl moieties, and on the nature of these aryl residues (preferably indole). The most active compound was evaluated for its activity against Candida albicans infection in mice.

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Section: Resultsmentioning

confidence: 98%

Antifungal and antibacterial activities of diarylamidine derivatives

Anné¹,

Clercq²,

Eyssen³

et al. 1980

Antimicrob Agents Chemother

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“…The bis-benzimidazoles used in the present study were synthesized according to previously described methods (6,9,18,19 Large-scale cultures were cultivated in outside in roller bottles (Bellco Glass, Inc., Vineland, N.J.), which provide a high surface area-to-volume ratio (10). Logarithmically growing trophozoites (2 x 106) were inoculated into each bottle containing approximately 625 ml of medium.…”

Section: Methodsmentioning

confidence: 99%

“…The bis-benzimidazoles used in the present study were synthesized according to previously described methods (6,9,18,19). The purity of the compounds was determined by high-performance liquid chroma-tography, elemental analyses, and nuclear magnetic resonance spectroscopy.…”

Section: Methodsmentioning

confidence: 99%

Structure-activity studies of dicationically substituted bis-benzimidazoles against Giardia lamblia: correlation of antigiardial activity with DNA binding affinity and giardial topoisomerase II inhibition

Bell

Dykstra

Naiman

et al. 1993

Antimicrob Agents Chemother

100

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Nine dicationically substituted bis-benzimidazoles were examined for their in vitro activities against Giardia lamblia WB (ATCC 30957). The potential mechanisms of action of these compounds were evaluated by investigating the relationship among in vitro antigiardial activity and the affinity of the molecules for DNA and their ability to inhibit the activity of giardial topoisomerase II. Each compound demonstrated antigiardial activity, as measured by assessing the incorporation of [methyl-3H]thymidine by giardial trophozoites exposed to the test agents. Three compounds exhibited excellent in vitro antigiardial activities, with 50%o inhibitory concentrations which compared very favorably with those of two currently used drugs, quinacrine HCI and metronidazole. Putative mechanisms of action for these compounds were suggested by the strong correlation observed among in vitro antigiardial activity and the affinity of the molecules for natural and synthetic DNA and their ability to inhibit the relaxation activity of giardial topoisomerase II. A strong correlation between the DNA binding affinity of these compounds and their inhibition of giardial topoisomerase II activity was also observed.Giardia lamblia is a common cause of endemic and epidemic diarrheal disease throughout the world. Some individuals harbor asymptomatic infections, while others may exhibit acute or chronic gastrointestinal disease. Four agents are presently used to treat giardiasis: the nitroimidazoles metronidazole and tinidazole, the nitrofuran furazolidone, and quinacrine HCl, an acridine. Many problems are associated with the currently used chemotherapeutic agents, including treatment failures, unpleasant side effects, activity against normal intestinal flora, and possible carcinogenicity. While treatment of symptomatic individuals is recommended, there is controversy as to whether asymptomatic cyst passers should be treated, especially in light of the problems associated with the antigiardial agents presently available. More-effective and less-toxic agents are therefore needed for the treatment of giardiasis.The search for new antigiardial agents has been aided by improvements in axenic culturing of the organism (13) and drug susceptibility testing (3,12). Among the classes of compounds recently examined for antigiardial activity are anthelminthic benzimidazoles (1,8,14,15) Washington, DC 20307. which are used at present to treat the infection (2). In addition, there was a strong correlation between the antigiardial activities of the pentamidine analogs and their affinity for calf thymus DNA and poly(dA) poly(dT). The ability of pentamidine to bind to DNA has been proposed as a mechanism of action for this and related compounds. Pentamidine and related molecules have also been identified as potential inhibitors of the activity of type II topoisomerases (7,17).A number of dicationically substituted bis-benzimidazoles, originally developed as protease inhibitors and DNA binding agents, were available in our laboratory for in vitro antimi...

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“…In the early 1970s Dann O et al [30][31][32] Tidwell RR et al found that the in vitro anti-trypanosomal activities of bisbenzofuran derivatives against Trypanosoma brucei rhodesiense, and cytotoxicity against mammalian cells depended on the position and the type of cationic substituents as well as the length of the carbon linker between aromatic moieties. As observed in most of the dicationic molecules, the N-substituted congeners were lesser cytotoxic than the unsubstituted diamidines whereas the N-alkylation of cationic fragments reduced the activity of compounds against T. brucei rhodesiense compared to pentamidine.…”

Section: Benzofuran Derivativesmentioning

confidence: 99%

Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances

Paliwal

Verma²,

Paliwal³

2011

Sci. Pharm.

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Human African Trypanosomiasis (HAT) also called sleeping sickness is caused by subspecies of the parasitic hemoflagellate Trypanosoma brucei that mostly occurs in sub-Saharan Africa. The current chemotherapy of the human trypanosomiases relies on only six drugs, five of which have been developed more than 30 years ago, have undesirable toxic side effects and most of them show drug-resistance. Though development of new anti-trypanosomal drugs seems to be a priority area research in this area has lagged far behind. The given review mainly focus upon the recent synthetic and computer based approaches made by various research groups for the development of newer anti-trypanosomal analogues which may have improved efficacy and oral bioavailability than the present ones. The given paper also attempts to investigate the relationship between the various physiochemical parameters and anti-trypanosomal activity that may be helpful in development of potent anti-trypanosomal agents against sleeping sickness.

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Trypanocide Diamidine mit vier Ringen in einem oder zwei Ringsystemen

Cited by 25 publications

References 26 publications

Antifungal and antibacterial activities of diarylamidine derivatives

Antifungal and antibacterial activities of diarylamidine derivatives

Structure-activity studies of dicationically substituted bis-benzimidazoles against Giardia lamblia: correlation of antigiardial activity with DNA binding affinity and giardial topoisomerase II inhibition

Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances

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