The activity of diguanidino and ‘reversed’ diamidino 2,5-diarylfurans versus Trypanosoma cruzi and Leishmania donovani

Stephens, Chad E.; Brun, Reto; Salem, Maha M.; Werbovetz, Karl A.; Tanious, Farial A.; Wilson, W. David; Boykin, David W.

doi:10.1016/s0960-894x(03)00319-6

Cited by 82 publications

(64 citation statements)

References 34 publications

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“…A recent study focused on the activity of reversed amidines (DB786, Figure 1H ) and a closely related diguanidine (DB711, Figure 1H ) showed that the amidines presented an in vitro higher dose-dependent activity (IC 50 in the low micromolar range) after 2 h of treatment of bloodstream trypomastigotes and intracellular amastigotes of the parasite [13] . The authors also confirmed previous results, which showed the superior trypanocidal activity of the dicationic molecules containing reversed amidine cationic groups, as compared with diguanidino cationic groups [90] . The main ultrastructural alterations in amidine treated parasites were found in the nucleus and in the mitochondrion [43] .…”

Section: American Trypanosomiasissupporting

confidence: 88%

“…The activity of 58 aromatic dications were examined in vitro against L. donovani and the results showed that the most potent compounds were DB75, 2,4-bis (4-amidinophenyl)furan and 2,5-bis (4-amidinophenyl)thiophene, with the later two being more effective than pentamidine. However, these compounds, as well as pentamidine, showed poor activity when tested against Leishmania -infected macrophages [90,96] . DB75 also displayed activity against promastigotes of L. amazonensis , and the N -phenyl substituted derivative -DB569 was even more active [8] .…”

Section: Leishmaniasismentioning

confidence: 99%

“…Reversed amidines and diguanidino 2,5-diarylfurans were evaluated in vitro against L. donovani and the results showed that while the diguanidino analogs were less active than pentamidine and furamidine, the reversed amidines displayed higher activity as compared with both control compounds [90] .…”

Section: Leishmaniasismentioning

confidence: 99%

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Antiparasitic activity of aromatic diamidines and their patented literature

Soeiro¹,

Souza²,

Boykin³

2007

Expert Opinion on Therapeutic Patents

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Aromatic diamidines and related compounds are DNA minor groove-binding binders that display excellent antimicrobial activity towards bacteria, fungi and protozoa. This review focuses on the activity and patented information related to aromatic diamidines (and analogs) towards four relevant parasitic protozoa, African and American trypanosomas, Leishmania and Plasmodium, which are parasites that still cause incurable neglected diseases annually killing millions of people in many developing countries. The overall data regarding aromatic diamidines argue for the development and screening of new diamidines and their corresponding prodrugs, which display lower toxicity and retain the low dose activity against these as well as other parasites.

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Section: American Trypanosomiasissupporting

confidence: 88%

Section: Leishmaniasismentioning

confidence: 99%

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Antiparasitic activity of aromatic diamidines and their patented literature

Soeiro¹,

Souza²,

Boykin³

2007

Expert Opinion on Therapeutic Patents

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“…Among them (see also Figure 1), aromatic amidines exhibit broad antimicrobial activity including antifungal [1], antibacterial [2], antiviral [3], and antiprotozoal [4,5] activities. However, despite the broad activity, toxicity of the diamidino compounds has restricted their clinic usage.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Potent Antimicrobial Activities of Some Novel Retinoidal Monocationic Benzimidazoles

Ateş‐Alagöz

Alp

Kuş

et al. 2006

Archiv der Pharmazie

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Several 2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-benzimidazole-5-carboxamidine analogues were synthesized for their antibacterial and antifungal activities against S. aureus, Methicillin-resistant S. aureus (MRSA), C. albicans, and C. krusei. MIC values of the targeted compounds 43-58 are comparable to those of Fluconazole and Sultamicillin. The most potent compounds, 51 and 53, showed MIC values as 0.78 and 1.56 microg/mL against S. aureus and C. albicans, respectively.

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“…Our laboratory has previously focused on antileishmanial activity of novel dications using an Leishmania donovani axenic amastigote model (Brendle et al, 2002;Stephens et al, 2003;Gonzalez et al, 2007). Several dicationic compounds exhibit improved activity compared to pentamidine against Leishmania species that cause visceral leishmaniasis and New World CL (Bell et al, 1990;Brendle et al, 2002;Rosypal et al, 2007), but their activities against etiologic agents of OWCL have not been examined.…”

mentioning

confidence: 99%

Inhibition by Dications of In Vitro Growth of Leishmania major and Leishmania tropica: Causative Agents of Old World Cutaneous Leishmaniasis

Rosypal¹,

Werbovetz²,

Salem³

et al. 2008

Journal of Parasitology

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Old World cutaneous leishmaniasis is caused by infection with Leishmania major and Leishmania tropica. Pentamidine and related dications exhibit broad spectrum antiprotozoal activity. Based on the previously reported efficacy of these compounds against related organisms, 18 structural analogs of pentamidine were evaluated for in vitro antileishmanial activity, using pentamidine as the standard reference drug for comparison. Furan analogs and reversed amidine compounds were examined for activity against L. major and L. tropica promastigotes. The most active compounds against both Leishmania species were in the reversed amidine series. DB745 and DB746 exhibited the highest activity against L. major and DB745 was the most active compound against L. tropica. Both of these compounds exhibited 50% inhibitory concentrations (IC50) below 1 nM for L. major. Ten reversed amidines were also tested for their ability to inhibit growth in an axenic amastigote model. Nine of 10 reversed amidine analogs were active at concentrations below 1 nM. These results justify further study of dicationic compounds as potential new agents for treating cutaneous leishmaniasis.

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The activity of diguanidino and ‘reversed’ diamidino 2,5-diarylfurans versus Trypanosoma cruzi and Leishmania donovani

Cited by 82 publications

References 34 publications

Antiparasitic activity of aromatic diamidines and their patented literature

Antiparasitic activity of aromatic diamidines and their patented literature

Synthesis and Potent Antimicrobial Activities of Some Novel Retinoidal Monocationic Benzimidazoles

Inhibition by Dications of In Vitro Growth of Leishmania major and Leishmania tropica: Causative Agents of Old World Cutaneous Leishmaniasis

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