The usefulness of cyclic diamidines with different core-substituents as antitumor agents

Spychala, Jaroslaw

doi:10.1016/j.bioorg.2008.05.002

Cited by 10 publications

(5 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Table 2 shows the observed 50% inhibitory concen- Figure 3A shows that all three compounds exhibit considerable toxicity in RH cell cultures. This is not surprising, since other studies have demonstrated toxic effects of diamidines in tumor cells, implying that toxicity was mediated by the nuclear or mitochondrial DNA-binding properties and topoisomerase inhibition (34)(35)(36). HFF, representing normal nontransformed cells, were more sensitive to DB1127 and DB871 than to DB869 (Fig.…”

Section: Resultsmentioning

confidence: 62%

In VitroandIn VivoActivities of Dicationic Diguanidino Compounds against Echinococcus multilocularis Metacestodes

Küster

Kriegel

Boykin

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

c Alveolar echinococcosis (AE) is a disease predominantly affecting the liver, with metacestodes (larvae) of the tapeworm Echinococcus multilocularis proliferating and exhibiting tumor-like infiltrative growth. For many years, chemotherapeutical treatment against alveolar echinococcosis has relied on the benzimidazoles albendazole and mebendazole, which require long treatment durations and exhibit parasitostatic rather than parasiticidal efficacy. Although benzimidazoles have been and still are beneficial for the patients, there is clearly a demand for alternative and more efficient treatment options. Aromatic dications, more precisely a small panel of di-N-aryl-diguanidino compounds, were screened for efficacy against E. multilocularis metacestodes in vitro. Only those with a thiophene core group were active against metacestodes, while furans were not. The most active compound, DB1127, was further investigated in terms of in vivo efficacy in mice experimentally infected with E. multilocularis metacestodes. This diguanidino compound was effective against AE when administered intraperitoneally but not when applied orally. Thus, thiophene-diguanidino derivatives with improved bioavailability when administered orally could lead to treatment options against AE.

show abstract

Section: Resultsmentioning

confidence: 62%

In VitroandIn VivoActivities of Dicationic Diguanidino Compounds against Echinococcus multilocularis Metacestodes

Küster

Kriegel

Boykin

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…5). This is not surprising, since other studies have demonstrated toxic effects of diamidines in tumor cells, implying that toxicity was mediated by the nuclear or mitochondrial DNA-binding properties and topoisomerase inhibition (3,37,46). In any case, toxicity of compounds against cell cultures cannot be automatically translated into the in vivo situation.…”

Section: Discussionmentioning

confidence: 95%

In Vitro Efficacy of Dicationic Compounds and Mefloquine Enantiomers against Echinococcus multilocularis Metacestodes

Lundström‐Stadelmann

Küster

Scholl

et al. 2011

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The current chemotherapy of alveolar echinococcosis (AE) is based on benzimidazoles such as albendazole and has been shown to be parasitostatic rather than parasiticidal, requiring lifelong duration. Thus, new and more efficient treatment options are urgently needed. By employing a recently validated assay based on the release of functional phosphoglucose isomerase (PGI) from dying parasites, the activities of 26 dicationic compounds and of the (؉)-and (؊)-erythro-enantiomers of mefloquine were investigated. Initial screening of compounds was performed at 40 M, and those compounds exhibiting considerable antiparasitic activities were also assessed at lower concentrations. Of the dicationic drugs, DB1127 (a diguanidino compound) with activities comparable to nitazoxanide was further studied. The activity of DB1127 was dose dependent and led to severe structural alterations, as visualized by electron microscopy. The (؉)-and (؊)-erythro-enantiomers of mefloquine showed similar dose-dependent effects, although higher concentrations of these compounds than of DB1127 were required for metacestode damage. In conclusion, of the drugs investigated here, the diguanidino compound DB1127 represents the most promising compound for further study in appropriate in vivo models for Echinococcus multilocularis infection.

show abstract

“…The solvent was removed under reduce pressure, and the residue was suspended in water and precipitated with acetone to yield 0. 16 …”

Section: 5-bis[n-(4-(1456-tetrahydropyrimidin-2-yl)phenyl)-carbomentioning

confidence: 99%

“…[6][7][8] Diarylamidines have a wide range of potential therapeutic applications, such as ACIS inhibitors, 9 antiparasitic, 10,11 antifungal, 12 antibacterial, 13,14 antiviral 15 and anticancer agents. 4,6,16,17 Until now, pentamidine, 1,5-bis(4-amidinophenoxy)pentane, is the only one of this class with significant human clinical use. The development of pentamidine as a therapeutic drug is limited due to its known toxic side effects as a consequence of parent drug metabolism.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, DNA Interactions and Anticancer Evaluation of Novel Diamidine Derivatives of 3,4-Ethylenedioxythiophene

Stolić¹,

Avdičević²,

Bregović³

et al. 2012

Croat. Chem. Acta

View full text Add to dashboard Cite

Abstract. Eight novel diamidino 3,4-ethylenedioxythiophene-2,5-dicarboxanilides (5a-h), obtained by condensation reaction of 3,4-ethylenedioxythiophene-2,5-dicarbonyl chloride and corresponding 3-or 4-aminobenzamidines, were evaluated for interactions with double-stranded DNA and RNA, and their cytotoxicity was assayed against the panel of human cancer cell lines. All compounds preferentially bind into the minor groove of DNA and had higher affinity for DNA than for RNA. Compounds 5a-h showed a moderate antiproliferative effect toward the panel of seven carcinoma cells line, whereby the highest inhibitory potential was displayed by compound 5a with unsubstituted amidino moieties in para position.

show abstract

The usefulness of cyclic diamidines with different core-substituents as antitumor agents

Cited by 10 publications

References 63 publications

In VitroandIn VivoActivities of Dicationic Diguanidino Compounds against Echinococcus multilocularis Metacestodes

In VitroandIn VivoActivities of Dicationic Diguanidino Compounds against Echinococcus multilocularis Metacestodes

In Vitro Efficacy of Dicationic Compounds and Mefloquine Enantiomers against Echinococcus multilocularis Metacestodes

Synthesis, DNA Interactions and Anticancer Evaluation of Novel Diamidine Derivatives of 3,4-Ethylenedioxythiophene

Contact Info

Product

Resources

About