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Keywords = bisbenzamidines

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11 pages, 627 KiB  
Article
Alkanediamide-Linked Bisbenzamidines Are Promising Antiparasitic Agents
by Jean Jacques Vanden Eynde, Annie Mayence, Madhusoodanan Mottamal, Cyrus J. Bacchi, Nigel Yarlett, Marcel Kaiser, Reto Brun and Tien L. Huang
Pharmaceuticals 2016, 9(2), 20; https://doi.org/10.3390/ph9020020 - 19 Apr 2016
Cited by 6 | Viewed by 5123
Abstract
A series of 15 alkanediamide-linked bisbenzamidines and related analogs was synthesized and tested in vitro against two Trypanosoma brucei (T.b.) subspecies: T.b. brucei and T.b. rhodesiense, Trypanosoma cruzi, Leishmania donovani and two Plasmodium falciparum subspecies: a chloroquine-sensitive strain (NF54) [...] Read more.
A series of 15 alkanediamide-linked bisbenzamidines and related analogs was synthesized and tested in vitro against two Trypanosoma brucei (T.b.) subspecies: T.b. brucei and T.b. rhodesiense, Trypanosoma cruzi, Leishmania donovani and two Plasmodium falciparum subspecies: a chloroquine-sensitive strain (NF54) and a chloroquine-resistant strain (K1). The in vitro cytotoxicity was determined against rat myoblast cells (L6). Seven compounds (5, 6, 10, 11, 12, 14, 15) showed high potency against both strains of T. brucei and P. falciparum with the inhibitory concentrations for 50% (IC50) in the nanomolar range (IC50 = 1–96 nM). None of the tested derivatives was significantly active against T. cruzi or L. donovani. Three of the more potent compounds (5, 6, 11) were evaluated in vivo in mice infected with the drug-sensitive (Lab 110 EATRO and KETRI 2002) or drug-resistant (KETRI 2538 and KETRI 1992) clinical isolates of T. brucei. Compounds 5 and 6 were highly effective in curing mice infected with the drug-sensitive strains, including a drug-resistant strain KETRI 2538, but were ineffective against KETRI 1992. Thermal melting of DNA and molecular modeling studies indicate AT-rich DNA sequences as possible binding sites for these compounds. Several of the tested compounds are suitable leads for the development of improved antiparasitic agents. Full article
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11 pages, 126 KiB  
Article
Bisbenzamidines as Antifungal Agents. Are Both Amidine Functions Required to Observe an Anti-Pneumocystis carinii Activity?
by Julien Laurent, Dimitri Stanicki, Tien L. Huang, Eduardo Dei-Cas, Muriel Pottier, El Mouktar Aliouat and Jean Jacques Vanden Eynde
Molecules 2010, 15(6), 4283-4293; https://doi.org/10.3390/molecules15064283 - 11 Jun 2010
Cited by 11 | Viewed by 9258
Abstract
A library of 19 novel 4-(4-phenylpiperazine-1-yl)benzamidines has been synthesized and evaluated in vitro against Pneumocystis carinii. Among these compounds, N-ethyl- and N-hexyl-4-(4-phenylpiperazine-1-yl)benzamidines emerged as the most promising compounds, with inhibition percentages at 10.0 µg/mL of 87% and 96%, respectively. Those [...] Read more.
A library of 19 novel 4-(4-phenylpiperazine-1-yl)benzamidines has been synthesized and evaluated in vitro against Pneumocystis carinii. Among these compounds, N-ethyl- and N-hexyl-4-(4-phenylpiperazine-1-yl)benzamidines emerged as the most promising compounds, with inhibition percentages at 10.0 µg/mL of 87% and 96%, respectively. Those compounds remained active at 0.1 µg/mL. Full article
(This article belongs to the Special Issue ECSOC-13)
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