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PubMed1999

Dequalinium vesicles form stable complexes with plasmid DNA which are protected from DNase attack.

Upon sonication, the antimicrobial and antineoplastic compound dequalinium forms vesicles (DQAsomes, Weissig et al., 1998). Dequalinium (1,1'-(1,10-decamethylene-bis-[aminoquinaldinium])-chloride) was shown to be a fluorophore with an emission maximum at 366 nm. Addition of DNA results in a characteristic quenching of its intrinsic fluorescence. After density gradient centrifugation a band of dequalinium (DQA) tightly associated with DNA is located between the DNA and DQA bands. DQA/DNA-complexes containing plasmid DNA at a molar ratio of DQA/DNA 6:1 are completely protected against DNase activity. Addition of negatively-charged lipids release intact DNA in the same manner as from cationic lipid/DNA complexes. As regards biological effects, DQAsomes show a differential cytotoxicity for normal and sarcoma cell lines. In vitro incubation with fluorescein-labeled oligodeoxynucleotides (5'-fluorescein-[GATC]5) showed an increased uptake of the tagged oligodeoxynucleotide if complexed with dequalinium. We hypothesize that the DQA/DNA complexes are well-suited for 'DQAsomal gene transfer' in vitro and in vivo. Noteworthy, they display an intrinsic antitumor activity manifested by differential cytotoxicity for normal and sarcoma cells.

Cell Survival↗

PubMed1981

The use of dequalinium acetate as a disinfectant and chemotherapeutic agent in endodontics.

Dequalinium compounds are known as chemotherapeutic and bactericidal agents. They are used in various areas of medicine and oral medicine for combating cases of mixed infections. Until now, results of basic research studies have been published whose objective was to examine the suitability of dequalinium preparations as cleansing agents and intracanal dressings for endodontic use. This article presents for the first time a number of selected cases from a clinical research study in which widespread periapical lesions revealed before the start of treatment were treated with a preparation whose active ingredient was dequalinium acetate. The results of treatment and follow-up are given. These case reports show that healing of the periapical lesions occurs relatively quickly and is generally completed within a period of 9 months.

Adult↗

PubMed1992

Effect of dequalinium on K1735-M2 melanoma cell growth, directional migration and invasion in vitro.

Cationic lipophilic compounds have an antiproliferative effect on certain tumour systems in vitro and in vivo. We have investigated whether the cationic lipophilic compound dequalinium affects not only proliferation but also motility and invasion of the highly metastatic and highly invasive melanoma cell line K1735-M2. Proliferation was assessed in monolayer cultures and in multicellular spheroids, motility was estimated in the assay of directional migration, and invasiveness was tested through confrontation cultures of tumour multicellular spheroids with embryonic chick heart tissue evaluated by computerized image analysis. 2 mumol/l dequalinium impaired melanoma cell proliferation, reduced directional migration and significantly blocked invasion in vitro. On the ultrastructural level, dequalinium caused obvious changes in mitochondria of both melanoma and embryonic chick heart cells. The mechanisms of the antiproliferative, antimigrating and antiinvasive effects remain to be determined. Inhibition of protein kinase C, calmodulin antagonism, DNA intercalation and/or direct effects on mitochondrial functions may be considered.

Animals↗

PubMed2006

Plasmodium berghei: in vitro and in vivo activity of dequalinium.

Bisquinoline compounds have exhibited remarkable activity in vitro and in vivo against Plasmodium parasites by inhibition of heme detoxification. We have tested the ability of dequalinium 1,1'-(1,10-decanediyl)bis(4-amino-2-methylquinoline), a known antimicrobial agent, to inhibit beta-hematin synthesis using a non-emzymatic colorimetric assay and globin proteolysis by electrophoretic analysis (SDS-PAGE-15%). Dequalinium was able to inhibit both processes in vitro with close correlation to a murine malaria model, reducing parasitemia levels, prolonging the survival time post-infection and curing 40% of infected mice using a combination therapy with a loading dose of chloroquine. These results confirm that dequalinium is a promising lead for antimalarial drug development.

Animals↗

PubMed1996

Synthesis and pharmacological testing of dequalinium analogues as blockers of the apamin-sensitive Ca(2+)-activated K+ channel: variation of the length of the alkylene chain.

Dequalinium is a potent and selective blocker of the small conductance Ca(2+)-activated K+ (SKCa) channel in rat sympathetic neurones. Analogues of dequalinium possessing 3-6, 8, 10, and 12 methylene groups in the linking chain have been synthesized and tested for inhibition of the afterhyperpolarization in rat sympathetic neurones. The compounds having a 5-12-carbon chain showed very little variation in their activity as SKCa channel blockers. The analogues possessing four and three methylenes exhibited 3- and 8-fold lower potency, respectively, compared with dequalinium. These results are discussed in the context of possible modes of binding of the compounds to the SKCa channel.

Action Potentials↗

PubMed1975

Microvascular response to local application of dequalinium chloride. A vital microscopical study of hamster's cheek pouch and a microangiographic study of rabbit's ear.

Dequalinium chloride is a topical antiseptic, whose use may be attended by skin necrosis. Since microcirculatory changes are an early and distinct manifestation of tissue injury, the tissue damaging effect of dequalinium chloride on the microcirculation was examined. The immediate vascular reactions were studied by vital microscopy, of the hamster cheek pouch and the late effects were visualized by microangiography of the rabbit ear. An aqueous solution of dequalinium chloride in concentrations well below those used in clinical practice induced severe microcirculatory disturbances.

Animals↗

PubMed1991

[Effects of dequalinium chloride and sanguinarine on the ultrastructure of early supragingival plaque].

The influence of antimicrobial mouthrinses containing dequalinium chloride or sanguinarine on early plaque formation was assessed in vivo in a clinical-experimental study. Rinses with water served as controls. After 24 and 72 hours, plastic films, which were applied to the buccal surfaces of six upper front teeth at the start of experiment, were removed and processed for transmission electron microscopic study. Dequalinium chloride or sanguinarine applied on plaque resulted in an increased and higher structured surface coating. Degenerated microorganisms were observed and the variety of bacteria seemed to be reduced. Both mouthrinses effected the early supragingival plaque formation. The effect of sanguinarine was more intensive than that of dequalinium chloride.

Adult↗

PubMed2001

Suramin prevents cerebellar granule cell-death induced by dequalinium.

In this study, we demonstrated that an anticancer drug, dequalinium, a bisquaternary ammonium compound, is a potent neurotoxicant with IC(50) of 0.46 microM on the cultured cerebellar granule neurons. Its selective neurotoxicity revealed by 100-fold more toxic than the other two analogs, pancuronium and vecuronium. The mechanisms underlying dequalinium (DQ)-induced neurotoxicity were explored and found to be associated with decreased mitochondrial membrane potential, increased free radical production and ATP depletion. Suramin (a nonselective purinergic P(2) receptor antagonist and an anticancer drug) but not the glutamate receptor antagonists, MK-801, NBQX (1,2,3,4 tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium), and DNQX (6,7-dinitroquinoxaline-2,3-dione) significantly prevents the DQ-induced neurotoxicity. By means of microfluorometric image-processing technique using the fluorescent probes, fluorescein diacetate/propidium iodide and Hoechst 33258, respectively, we showed that 1 microM DQ for 24 h induced about 53.5% of apoptosis and 37.5% of necrosis. All of these effects of DQ can be completely prevented by suramin. From these results, we conclude that DQ-induced neurotoxicity was not mediated by glutamate receptor, but by increasing free radical productions and cell energy depletion. Suramin with its beneficial antagonistic effects on DQ-induced neurotoxicity may provide an effective approach for neurodegeneration.

Adenosine Triphosphate↗

PubMed2003

In vivo biodistribution of erythrocytes and polyethyleneglycol-phosphatidylethanolamine micelles carrying the antitumour agent dequalinium.

Dequalinium (DQA), a lipophilic drug with anti-cancer activity has been incorporated into mouse red blood cells (DQA-RBCs) and polyethylene glycol phosphatidylethanolamine micelles (DQA-PEG-PE-micelles) in order to overcome the drug's solubility problems and to make it suitable for in vivo applications. The incorporation of DQA into erythrocytes, the release of DQA from RBCs in the presence of autologous plasma and the biodistribution of 51Cr-DQA-RBCs and 111In-DQA-PEG-PE micelles in mice has been studied. Under optimal conditions, up to 84.9% of 0.2 mM dequalinium can be incorporated into erythrocytes. The incubation of DQA-RBC with serum leads to the release of DQA over a period of 24 h. Since 51Cr-DQA-RBCs were found to have a long circulation half-life (5-6 days), the use of RBCs as a sustained release system for DQA can be suggested. In contrast to DQA containing erythrocytes, however, DQA loaded 111In-PEG-PE micelles displayed a shorter half-life (4 h) due to their quick uptake by the liver. The further exploration of PEG-PE micelles as a fast acting release system for DQA appears warranted.

Animals↗

PubMed1995

Synthesis and structure-activity relationships of dequalinium analogues as K+ channel blockers. Investigations on the role of the charged heterocycle.

Small conductance Ca(2+)-activated K+ (SKCa) channels occur in many cells but have been relatively little studied. Dequalinium, a bis-quinolinium compound, has recently been shown to be the most potent nonpeptidic blocker of this K+ channel subtype. This paper examines the importance of the quinolinium rings for blocking activity. Analogues of dequalinium were synthesised in which one quinolinium group was removed (1 and 2) or replaced by a triethylammonium group (3). They have been assayed in vitro for their ability to block the after-hyperpolarization (mediated by the opening of SKCa channels) that follows the action potential in rat sympathetic neurones. The compound having one quinolinium and one triethylammonium group (3) showed reduced activity, and it is suggested that the stronger binding to the channel of the quinolinium relative to the triethylammonium group may be related to differences in their electrostatic potential energy maps. Two monoquaternary compounds (1 and 2) were tested, but they exhibited a different pharmacological profile that did not allow definite conclusions to be drawn concerning their potency as blockers of the SKCa channel. Replacement of both quinolinium groups by pyridinium, acridinium, isoquinolinium, or benzimidazolium reduced but did not abolish activity. These results show that compounds having a number of different heterocyclic cations are capable of blocking the SKCa channel. However, among the heterocycles studied, quinoline is optimal. Furthermore, charge delocalization seems to be important: the higher the degree of delocalization the more potent the compound.

Animals↗

PubMed1995

Synthesis and quantitative structure-activity relationships of dequalinium analogues as K+ channel blockers: investigation into the role of the substituent at position 4 of the quinoline ring.

Dequalinium (4) is a potent and selective blocker of small conductance Ca2+-activated K+ channels, an important but relatively little studied class. The 4-NH2 group of dequalinium has been shown to contribute significantly to blocking potency. In this study, we have investigated further the role of the 4-NH2 group. Replacement of this group by other substituents (R4) and quantitative structure-activity relationship (QSAR) analysis on the resultant analogues have yielded a correlation between blocking potency and sigma R for R4 for seven of the compounds. The application of calculated electronic indices enabled the extension of the QSAR to compounds for which the appropriate sigma R values are not available, allowing all 13 analogues of this series to be included in the correlations. Analysis using electronic indices obtained from AM1 MO calculations on model compounds revealed that the blocking potency correlates with the partial charge on the ring N atom, ELUMO, and EHOMO. The EHOMO correlation is qualitatively inconsistent as the HOMO is not the same orbital in all compounds. The ELUMO correlation [pEMR = 1.19(+/- 0.21)ELUMO + 5.41(+/- 1.05), n = 13, r = 0.86, s = 0.274] suggests that the higher the ELUMO the more potent is the analogue. This is consistent with simple charge transfer from the channel to the blocker and may refer to other processes which are important for the strength of the drug-K+ channel interaction such as the desolvation of the compounds.

Animals↗

PubMed1996

Synthesis, molecular modeling, and K+ channel-blocking activity of dequalinium analogues having semirigid linkers.

Dequalinium [1,1'-(decane-1, 10-diyl)bis(2-methyl-4-aminoquinolinium)] is an effective blocker of the small conductance Ca2(+)-activated K+ channel. It has been shown that the number of methylene groups in the alkyl chain linking the two quinolinium rings of this type of molecule is not critical for activity. To further investigate the role of the linker, analogues of dequalinium have been synthesized, in which the alkyl chain has been replaced by CH2XCH2 where X is a rigid or semirigid group containing aromatic rings. The compounds have been tested for blockade of the slow after-hyperpolarization on rat sympathetic neurons. The most potent compounds have X = phenanthryl, fluorenyl, cis-stilbene, and C6H4(CH2)nC6H4, where n = 0-4. The conformational preferences of the compounds were investigated using the XED/COSMIC molecular modeling system. Although there is some dependence of the potency of the analogue on the conformational properties of the linker (X), overall, X groups having substantial structural differences are tolerated. It seems that X provides a support for the two quinolinium groups and does not interact with the channel directly. The intramolecular separation between the quinolinium rings, which is provided by rigid groups X, is not critical for activity; this may be attributed to the residual conformational mobility of the heterocycles and to the extensive delocalization of the positive charge. These two factors may permit favorable contacts between the quinolinium groups and the channel over a range of intramolecular separations.

Animals↗

PubMed1997

Determination of the quaternary ammonium compounds dequalinium and cetylpyridinium chlorides in candy-based lozenges by high-performance liquid chromatography.

The retention behavior of the quaternary ammonium compounds benzalkonium chloride, cetylpyridinium chloride and dequalinium chloride on a 100 x 4.6 mm id cyanopropyl stationary phase column is reported as a function of organic modifier and ionic hydrophobic mobile phase additive concentrations. Optimum liquid chromatographic mobile phases using different mobile phase additives are reported which are suitable for the determination of cetylpyridinium chloride and dequalinium chloride in a variety of candy-based lozenge formulations. The quantitative aspects of assays based on the separation of active ingredients and formulation excipients were established. The generality of application of the assay methods was evaluated by determining the quaternary ammonium content of different lozenges and comparing the values obtained with the stated dose.

Anti-Infective Agents, Local↗

PubMedDate not supplied

Isothermic titration calorimetry to study CMCs of neutral surfactants and of the liposome-forming bolaamphiphile dequalinium.

Isothermic titration calorimetry was used to measure the heat of micelle formation (molar enthalpy of transfer of surfactants monomers from water into micellar aggregates. The problems associated with the estimation of the CMC and the whole therodynamic profile of micellization of surfactants via Gibbs-Helmholtz-Equation are discussed. CMC's of octylthioglucoside and the peculiar bolaamphilphile dequalinium which concentrates in mitochondria are measured. In contrast to earlier reports, no CMC of dequalinium could be found inspite of extensive systematic measurements.

Anti-Infective Agents, Local↗

PubMedDate not supplied

Comparative in vitro evaluation of dequalinium B, a new boron carrier for neutron capture therapy (NCT).

A boronated derivative of dequalinium, a delocalized lipophilic cation (DLC), was synthesized as a potential boron carrier for the selective targeting of mitochondria in malignant versus benign cells for boron neutron capture therapy (BNCT), a binary modality for the treatment of cancer. This agent, designated DEQ-B, was taken up and retained in vitro in the KB, F98, and C6 tumor cell lines but not in the normal epithelial cell line CV1. DEQ-B was also less toxic in the latter cell line at lower exposure concentrations The uptake, retention, and toxicity profiles of DEQ-B are comparable to those of the non-boronated DLCs, dequalinium, MKT 077, RH 123, and tetraphenylphosphonium chloride. Our results suggest that the synthesis and further evaluation of boronated DLCs as potential delivery agents for BNCT is warranted.

Animals↗

PubMedDate not supplied

[Antimicrobial characteristics of a tincture of dequalinium chloride].

Dequalinium is a quaternary ammonium salt. From about 30 years Dequalinium (D.C.) was used in the treatment of the initial respiratory organs infections. It can be given orally and topically yet it cannot be given systemically cause its probable systemic toxicity. D.C. has a wide range of antimicrobial activity that is extended to Gram positive, Gram negative bacteria, protozoa and yeast. Its mechanism of action is directed to the cytoplasmatic membrane where D.C. caused its damage and consequently release of cellular components. Our study has been evaluated the antimicrobial activity of D.C. both as commercial product that pure substance. We tested 27 Gram positive bacteria, 49 Gram negative bacteria, 83 strains of fungi, we also tested the antimicrobial activity of D.C. commercial product and pure substance against 8 strains of protozoa; Trichomonas vaginalis. The antimicrobial activity was estimated in some experimental conditions, (cultural and no cultural conditions); in these experiments we can observed that the commercial product presents higher activity than pure substance. In cultural condition commercial product presents antimicrobial activity against Gram positive and negative bacteria and yeast; its interesting to evaluate that bacteria, that are resistant to the common antimicrobial agents were inhibited by D.C. tinture and pure substances. Our data exhibit that serum didn't interfere until the 2% concentration with the antimicrobial activity of D.C., moreover this antimicrobial activity is not influenced by the inoculum size until 10(5) cell/ml. D.C. presents higher activity at alkaline pH than acid pH but strains of C. albicans were killed by D.C. at acid pH. In no cultural conditions D.C. has demonstrated a rapid antimicrobial activity in short contact time (15 minute); the cells of some microorganisms were killed in 60 minutes. Against mycelial form, the commercial product demonstrates good activity higher than pure substance. The activity of D.C. against the formation of germ-tube from blastospores of C. albicans in N-acetyl-glucosamine solution (no culture medium) was markedly high; this is very important because in C. albicans the germ-tube production and yeast-mycelial conversion are prominent for pathogenicity and resistance to host defences. Our data demonstrate the good activity of D.C. against Trichomonas vaginalis; we can also observed that the antimicrobial activity of commercial product is higher than pure substance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1977

[Treatment of tonsillitis with dequalinium chloride].

44 children with acute tonsillitis were treated without the usual penicillin therapy. 22 children received lozenges containing Dequalinium chloride, 22 children received void lozenges under conditions of a double blind study. The results show that the treatment with Dequalinium chloride did not influence conditions caused by haemolytic streptococci -- verified by bacteriological examinations of pharyngeal smears -- inspite of its efficiency in vitro. Also general symptoms like fever, leukocytosis and rapid erythrocyte sedimentation rate were not influenced by Pequalinium chloride. Local symptoms like sore throat, tonsillar redness and exsudation were influenced beneficially. It can therefore be assumed that in cases of acute tonsillitis penicillin therapy is not necessary except in cases of streptococci infections. These should be excluded by pharyngeal smear. The medium of Liebermeister and Braveny is a very simple indicator to differentiate between tonsillitis caused by streptococci and tonsillitis of other origin.

Child↗

PubMed1995

A nuclear magnetic resonance method for the determination of the purity of commercial dequalinium chloride.

4-amino-1-(10-4'-quinaldinylaminodecyl)quinaldinium chloride (3) has been identified through nuclear magnetic resonance (NMR) studies as one of the impurities of a commercial sample of dequalinium chloride (CAS 522-51-0). The NMR technique is proposed as a rapid method for the recognition and quantification of the impurities in dequalinium chloride samples.

Chromatography, High Pressure Liquid↗