Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Dequalinium”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1991

[The efficacy of dequalinium chloride/benzalkonium chloride as well as medicinal plants on the gingiva].

A comparative study involving 50 patients of both genders was conducted in order to determine the effect of dequalinium chloride/benzalconium chloride mouthrinse (Dequonal), and of a preparation of herbal essences (Parodontax) on gingival health. Each of the mouthrinses was used during four weeks by a group of 25 patients who were instructed to abstain from any other oral hygiene measure during this period. Approximal plaque index, sulcus bleeding index and saliva pH were significantly enhanced by both preparations. A slightly better effect shown by dequalinium chloride/benzalconium chloride was not significant.

Adult↗
PubMed2000

Site of action of suramin and reactive blue 2 in preventing neuronal death induced by dequalinium.

Dequalinium (DQ, an anticancer drug) is a potent neurotoxicant in the cultured developing cerebellar granule neurons (CGNs) with an IC(50) of 1.31. M after 24 hr incubation. By utilizing fluorometric technique, we found that DQ initially induced apoptosis and then necrosis associated with a marked decrease in ATP contents. The purinergic P(2) receptor antagonists (suramin, and reactive blue 2) prevented DQ-cytotoxicity, although glutamate ionotropic receptor antagonists (MK 801 and NBQX) could not. Furthermore, we quantitatively determined a reduction of mitochondrial membrane potential and an increase of free radical production induced by DQ. Suramin abolished these detrimental events of DQ. This suggests that neuronal death induced by DQ is mediated, at least in part, through a signaling pathway of free radical production-mitochondrial dysfunction. Further evidence supporting this contention is that CGN progressively became more sensitive to both DQ-induced cytotoxicity and reduced mitochondrial membrane potential. This implies that neuronal mitochondria are apparently one of the target sites for DQ and suramin and directly or indirectly induce neurotoxicity and neuroprotection respectively. The alteration in mitochondrial membrane potential during neuronal maturation may be one of the determinants accounting for the increased susceptibility to neurotoxicants such as DQ.

Adenosine Triphosphate↗
PubMed1993

Toxicity of the mitochondrial poison dequalinium chloride in a murine model system.

Dequalinium chloride (DECA), a cationic, lipophilic mitochondrial poison, selectively targets the mitochondrial membrane of certain epithelial carcinoma cells, in which it inhibits cellular energy production. It has demonstrated potency as a cytotoxic agent specific for carcinomas and may provide a novel approach for cancer therapy, either as a single agent or as an adjunct to conventional chemotherapy. The purpose of this study was to determine the toxicity of DECA in the murine model. One hundred female BALB/c mice were divided into three schedule groups. Group one received a single intraperitoneal (ip) dose of DECA at 10, 15, 20, or 25 mg/kg of body weight. Group two received DECA at 6, 7, 8, 9, or 10 mg/kg ip every other day (QOD), and group three received DECA at 10, 11, 12, 13, or 14 mg/kg ip every 7 days. Over a 30- to 60-day period, acute and subchronic toxicities were evaluated on the basis of the following clinical parameters: respiratory distress, weight loss, and mortality. After a single ip administration, we found a maximum tolerated dose of 15 mg/kg and a lethal dose (LD50) of 18.3 mg/kg. Single ip doses of 20 and 25 mg/kg produced > 50% mortality. Histologic examination of the tissues revealed significant damage to the liver and kidneys, with pulmonary congestion occurring secondary to renal-hepatic failure. A cumulative assessment revealed that 60% of the animals tolerated 15 doses of 6 and 7 mg/kg QOD and that 100% tolerated 5 doses of 11 and 12 mg/kg (every 7 days). Higher DECA doses under either regimen induced severe toxic effects and mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Dequalinium induces a selective depletion of mitochondrial DNA from HeLa human cervical carcinoma cells.

Treatment of cultured human cervical carcinoma cells with the anticancer drug dequalinium (DEQ) was found to cause a delayed inhibition of cell growth. This inhibition was preceded by a loss of mitochondrial DNA (mtDNA), a decrease in cytochrome c oxidase activity, and an increase in the level of lactate, indicating that growth inhibition was due to the loss of mtDNA-encoded functions. There was a progressive two-fold loss of mtDNA following each cell division in the presence of DEQ, suggesting that this drug was acting by inhibiting some aspect of mtDNA synthesis. Furthermore, cells became resistant to the growth inhibitory and cytotoxic affects of DEQ when they were grown under conditions that bypassed the need for mtDNA-encoded functions. Resistance was not associated with significant changes in drug accumulation. These results suggest that the DEQ-induced depletion of mtDNA plays an important role in drug cytotoxicity.

Antineoplastic Agents↗
PubMed1993

Failure to enhance the in vivo killing of human ovarian carcinoma by sequential treatment with dequalinium chloride and tumor necrosis factor.

Dequalinium chloride (DECA) is a cationic, lipophilic compound with structure similar to the dye rhodamine 123. DECA is selectively accumulated and retained within the mitochondria of carcinoma cells where it acts as a mitochondrial poison by blocking mitochondrial enzymes which can then disrupt cellular energy production, eventually resulting in cell death. In this manner it is similar to the antimitochondrial effects observed with tumor necrosis factor (TNF). We have previously shown that DECA can synergize the in vitro antitumor effects of TNF against a panel of human ovarian cancer cell lines. Those drug studies have been extended to a xenogenic tumor system with a resultant increase in animal survival. Athymic mice were injected intraperitoneally with 2.0 x 10(7) PA-1 human ovarian cancer cells and DECA +/- TNF treatments begun either on Days 3 or 7 postinjection. Peritoneal tumor implantation was not histologically confirmed by Day 3 postinjection but confirmed by Day 7 following tumor cell injection. Single-agent DECA (5 mg/kg; qod) increased animal survival by 37% (P = 0.002) whereas recombinant human TNF (0.5 micrograms/mouse; qod) only increased survival by 13% (P = 0.27) relative to control animals for those animals treated 3 days post-tumor-injection. Sequential DECA/TNF enhanced animal survival by 45% (P = 0.0002) in similarly treated animals. When drug treatment was initiated 7 days following tumor injection, DECA increased survival by 23% (P = 0.04) while TNF had no effect on prolonging animal survival (3% increase; P = 0.79). Combination DECA/TNF increased survival by 23% (P = 0.04). In the UCI-101 ovarian tumor model, single-agent DECA increased survival by 28% (P = 0.04) while TNF treatment stimulated tumor growth (11% decrease in survival; P = 0.006). Combination DECA + TNF resulted in a 41% increase in survival (P = 0.003). No statistical differences were detected between survival rates for single-agent DECA vs DECA + TNF except for the UCI-101 tumor which showed potentiation due to the in vivo stimulatory effects of TNF.

Animals↗
PubMed1986

Comparative study of the configuration and the cleanliness level of root canals prepared with the aid of sodium hypochlorite and bis-dequalinium-acetate solutions.

Bis-dequalinium acetate (BDA), a quaternary ammonium compound, was introduced as a bactericidal and chemotherapeutic agent for endodontic use. This study was undertaken to compare the efficacy of this compound to 5.25% sodium hypochlorite in the cleansing and shaping of root canals. One hundred twenty freshly extracted teeth were divided into three groups. Each group was treated with the aid of the test material; saline solution was used as a control. After completion of the endodontic preparation, a silicone imprint of the canals was performed and the teeth were decalcified. The imprints were examined three-dimensionally to determine the amount of debris and canal configuration due to defective preparation and anatomic variation. No significant difference could be observed between the tested materials with respect to cleanliness and the shape of the canals. At the apical third, however, the BDA-treated canals showed more favorable results with respect to cleanliness. On the basis of the present and previous findings, it was concluded that BDA might be a favorable replacement for sodium hypochlorite as an irrigation solution.

Dental Pulp Cavity↗
PubMed2006

Inhibition of protein kinase C by dequalinium analogues: structure-activity studies on head group variations.

New dequalinium analogues and related heteroaromatic systems were synthesized and evaluated for inhibition of protein kinase Calpha. In vitro assays with recombinant human PKCalpha showed that the number of the aromatic ring head groups as well as their electron-richness, are critical factors that determine potency. The inhibitory strengths of the synthesized compounds are shown to correlate well with Mulliken charges on the head group ring nitrogen atoms making it possible to design likely candidate molecules having improved protein kinase Calpha inhibitory activity.

Dequalinium↗
PubMed2005

Effects of the antitumoural dequalinium on NB4 and K562 human leukemia cell lines. Mitochondrial implication in cell death.

Dequalinium (DQA) is a delocalized lipophylic cation that selectively targets the mitochondria of carcinoma cells. However, the underlying mechanisms of DQA action are not yet well understood. We have studied the effects of DQA on two different leukemia cell lines: NB4, derived from acute promyelocytic leukemia, and K562, derived from chronic myeloid leukemia. We found that DQA displays differential cytotoxic activity in these cell lines. In NB4 cells, a low DQA concentration (2microM) induces a mixture of apoptosis and necrosis, whereas a high DQA concentration (20microM) induces mainly necrosis. However, K562 cell death was always by necrosis as the cells showed a resistance to apoptosis at all time-periods and DQA concentrations assayed. In both cell lines, the cell death seems to be mediated by alterations of mitochondrial function as evidenced by loss of mitochondrial transmembrane potential, O2*- accumulation and ATP depletion. The current study improves the knowledge on DQA as a novel anticancer agent with a potential application in human acute promyelocytic leukemia chemotherapy.

Adenosine Triphosphate↗
PubMed2005

Induction of petite mutants in yeast Saccharomyces cerevisiae by the anticancer drug dequalinium.

Dequalinium (DEQ), a drug with both antimicrobial and anticancer activity, induced the formation of petite (respiration-deficient) mutants in the yeast Saccharomyces cerevisiae. DEQ was found to be approximately 50-fold more potent than ethidium bromide (EB) at inducing petites. Analysis of the DEQ-induced petite mutants indicated a complete loss of mitochondrial DNA (<1 copy/cell). Prior to the loss of mtDNA, DEQ caused cleavage of the mtDNA into a population of fragments 30-40kbp in size suggesting that this drug causes petites by inducing a breakdown of mtDNA. The selective effect of DEQ on yeast mtDNA may underlie the antifungal activity of this chemotherapeutic agent.

Antineoplastic Agents↗
PubMed2005

Flow injection spectrofluorimetric study of the supramolecular interaction between beta-cyclodextrin and dequalinium chloride and its analytical application.

The supramolecular interaction of dequalinium chloride (DQC) and beta-cyclodextrin has been studied by flow injection spectrofluorimetry. The results showed that beta-CD reacted with DQC to form a 1:1 host:guest complex with an apparent association constant of 4.99 x 10(2) L mol(-1). Based on the enhancement of the fluorescence intensity of DQC, a flow injection spectrofluorometric method for the determination of DQC in bulk aqueous solution in the presence of beta-CD was developed. The linear range was 0.0412-30.00 microg mL(-1). The detection limit was 12.3 ng mL(-1) with a sampling rate of 80 h(-1). There was no interference from the excipients normally used in tablets and serum compositions. The proposed method was successfully applied to the determination of DQC in tablets and serum.

Chromatography, Gas↗
PubMed1993

Photoinactivation of the bovine heart mitochondrial F1-ATPase by [14C]dequalinium cross-links phenylalanine-403 or phenylalanine-406 of an alpha subunit to a site or sites contained within residues 440-459 of a beta subunit.

Synthesis of [14C]dequalinium, 1,1'-(1,10-[1,10-14C]decanediyl)bis[4-amino-2-methylquinolinium ], is described, which photoinactivates the bovine heart mitochondrial F1-ATPase (MF1). Maximal photoinactivation occurs on incorporation of about 1.5 mol of [14C]dequalinium/mol of MF1. Three radioactive species were resolved when photoinactivated enzyme was submitted to polyacrylamide gel electrophoresis at pH 4.0 in the presence of tetradecyltrimethylammonium bromide, which correspond to the alpha and beta subunits and a cross-linked species with an M(r) of 116,000. Fractionation of a tryptic digest of photoinactivated enzyme by high-performance liquid chromatography led to isolation of a radioactive peptide which contains residues 399-420 of a alpha subunit. Two fragments containing equal amounts of radioactivity were obtained on fractionation of an endoproteinase Asp-N digest of the isolated radioactive tryptic peptide by high-performance liquid chromatography. Amino acid sequence analysis showed that both fragments contained residues 399-408 of the alpha subunit, but one was missing Phe-alpha 403 and the other was lacking Phe-alpha 406. Fractionation of a cyanogen bromide digest of photoinactivated enzyme followed by trypsin digestion of partially purified cyanogen bromide fragments and fractionation of the resulting radioactive tryptic fragments yielded several radioactive species comprised of residues 399-420 of the alpha subunit cross-linked to residues 440-459 of the beta subunit and a radioactive fragment containing residues 399-420 of the alpha subunit. Partial sequence analyses of the cross-linked fragments suggest that Phe-alpha 403 and Phe-alpha 406 participate in cross-links, whereas no information was obtained on the site or sites of cross-linking in the beta subunit fragment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed2000

Inhibition of protein kinase C(alpha) by dequalinium analogues: dependence on linker length and geometry.

Analogues of a bipartite compound, dequalinium (DECA) (quinolinium, 1,1'-(1,10-decanediyl)bis(4-amino-2-methyl diiodide)), were tested for inhibition of protein kinase C(alpha) (PKC(alpha)). In vitro assays of monomeric and dimeric analogues support a model in which DECA inhibits PKC(alpha) by an obligatory two-point contact, a unique mechanism among PKC inhibitors. The presence of unsaturation in the center of the C(10)-alkyl linker produced geometric isomers with different inhibitory potencies: cis IC(50) = 52 +/- 12 microM and trans IC(50) = 12 +/- 3 microM, where the trans isomer was equipotent to that of the saturated C(10)-DECA. DECA analogues with longer, saturated linkers (C(12), C(14), or C(16)) exhibited enhanced inhibitory potencies which reached a plateau with the C(14)-linker (IC(50) = 2.6 +/- 0.2 microM). Metastatic melanoma cells treated with 250 nM C(12)-, C(14)-, or C(16)-DECA and irradiated with long-wave UV light (which causes irreversible inhibition of PKC(alpha) by DECA) confirmed the linker-dependent inhibition of intracellular PKC(alpha) activity.

Animals↗
PubMed2002

Local treatment of vaginal infections of varying etiology with dequalinium chloride or povidone iodine. A randomised, double-blind, active-controlled, multicentric clinical study.

This randomised, double-blind, multicentric clinical study compared the efficacy and tolerability of the two vaginal antiseptics, 10 mg dequalinium chloride (CAS 522-51-0, Fluomycin N) and 200 mg povidone iodine (CAS 25655-41-8), in a parallel-group design. A total of 180 patients with vaginal infections of varying etiology participated in this study (bacterial vaginosis, fluor vaginalis, vulvo-vaginal candidiasis, trichomoniasis). Patients were randomly allocated to one of the two treatment groups and were treated once per day for 6 days. Control examinations took place 5 to 7 days after the end of treatment, and 3 to 4 weeks after the first control examination. The total symptoms score, a summary score for the clinical symptoms, discharge, burning, pruritus, redness of vulva/vagina, was defined as primary efficacy parameter. The treatments at the first control examination were compared in the full analysis set using the Wilcoxon-Mann-Whitney U-test, 2-sided, thereby proving equivalence of both treatments at the 5% level. Both treatments strongly improved the symptoms of vaginal infections both on short-term and long-term follow-up. Descriptive analysis of the secondary parameters, vaginal pH, degree of purity of the vaginal flora, and number of lactobacilli in the wet mounts, supported the comparable efficacy of both therapies to restore the vaginal milieu. Analysis of the diagnostic subgroups indicated that irrespective of the diagnosis, both treatments improved the efficacy criteria as observed for the entire population. The global assessment of the therapeutic efficacy by investigators and patients supported the results of the efficacy analysis with good to very good ratings in 70-90% of the cases. A good tolerability of both preparations was observed in this study with a low number of adverse events in the test group (5.8%).

Adolescent↗
PubMed1998

Photoinduced inactivation of protein kinase C by dequalinium identifies the RACK-1-binding domain as a recognition site.

1,1'-Decamethylenebis-4-aminoquinaldinium diiodide (DECA; dequalinium) is an anti-tumor agent and protein kinase C (PKC) inhibitor whose mechanism of action with PKC is unknown. This study reports that with human PKC alpha, DECA exhibited competitive inhibition (Ki = 11.5 +/- 5 microM) with respect to RACK-1 (receptor for activated C kinase-1), an adaptor protein that has been proposed to bind activated PKC following translocation (Ron, D., Luo, J., and Mochly-Rosen, D. (1995) J. Biol. Chem. 270, 24180-24187). When exposed to UV light, DECA covalently modified and irreversibly inhibited PKC (alpha or beta), with IC50 = 7-18 microM. UV/DECA treatment of synthetic peptides modeled after the RACK-1-binding site in the C2 region of PKC beta induced modification of Ser218-Leu-Asn-Pro-Glu-Trp-Asn-Glu-Thr226, but not of a control peptide. This modification occurred at a tryptophan residue (Trp223) that is conserved in all conventional PKC isoforms. In overlay assays with native RACK-1 that had been immobilized on nitrocellulose, UV-treated control PKC alpha bound well to RACK-1, whereas UV/DECA-inactivated PKC alpha had reduced binding activity. The significance of these findings is shown with adenocarcinoma cells, which, when pretreated with 10 microM DECA and UV light, exhibited diminished 12-O-tetradecanoylphorbol-13-acetate-induced PKC alpha translocation. Overall, this work identifies DECA as a tool that prevents PKC translocation by inhibiting formation of the PKC.RACK-1 complex.

Amino Acid Sequence↗
PubMed2000

Photo-induced inactivation of protein kinase calpha by dequalinium inhibits motility of murine melanoma cells.

Dequalinium (DECA) is a potent antitumor agent and inhibitor of protein kinase C (PKC). Previously it was shown that PKCalpha activity in vitro could be irreversibly inhibited when treated with DECA at low micromolar concentrations and irradiated with 366 nm of light. This approach was used to probe the role of intracellular PKC activity in the motility of metastatic murine melanoma B16 F10 cells and as a target for DECA analogs with increasing PKC inhibitory potencies. Pretreatment of a monolayer of B16 F10 cells with 250 nM of a DECA analog in the presence of UV irradiation for 5 min resulted in 1) complete inhibition of cell motility for up to 4 h in a time-lapse motility assay and 40 to 60% inhibition of cell migration in a Boyden chamber, and 2) inhibition by 40 to 60% of intracellular phosphatidylserine/Ca(2+)-dependent PKC catalytic activity, signifying inactivation of a conventional PKC isoform. Because PKCalpha is the only conventional PKC isoform detected in B16 F10 cells, a stably transfected clone expressing a kinase-defective mutant of PKCalpha was developed that exhibited a substantial loss of adhesion and motility and was refractory to further inhibition by DECA. These findings identify PKCalpha catalytic activity both as a mechanistic component of cell motility and adhesion and as a critical intracellular target of DECA. These studies further suggest that the combined use of UV with nanomolar concentrations of DECA offers an effective chemotherapeutic approach to inhibit metastatic behavior of melanoma cells.

Animals↗
PubMed1989

Inhibition of bovine heart mitochondrial and Paracoccus denitrificans NADH----ubiquinone reductase by dequalinium chloride and three structurally related quinolinium compounds.

1. Dequalinium chloride (DECA) and three related quinolinium compounds inhibit bovine heart mitochondrial and Paracoccus denitrificans electron transport activity, with inhibition localized between NADH and ubiquinone in both electron transport chains. 2. Structure-activity studies reveal that two quinolinium rings and a long bridging group are necessary for significant inhibition of reduction of artificial electron acceptors and coenzyme Q, whereas only one quinolinium ring and a long hydrocarbon side chain are required for significant inhibition of NADH oxidase activity. 3. Inhibition of coenzyme Q reduction by DECA is not reversed by dialysis. 4. Studies comparing DECA inhibition of rotenone-sensitive with rotenone-insensitive preparations indicate that DECA acts by a different inhibitory mechanism than rotenone on mammalian mitochondrial and P. denitrificans NADH----ubiquinone reductase.

Animals↗
PubMed1969

Mode of action of the antibacterial compound dequalinium acetate.

Dequalinium acetate is taken up rapidly by bacterial cells. Unlike the membrane-active drugs exemplified by cetrimide or chlorhexidine, its capacity for damaging the plasma membrane is low. The drug appears to penetrate quite rapidly into the cytoplasm where its effect seems to be exerted. A review of the evidence obtained in this study suggests that nucleic acid-containing components of the cell may be the prime target of this compound.

Anti-Bacterial Agents↗
PubMed1983

Quantitative evaluation of the influence of dequalinium acetate and sodium hypochlorite on human dentition.

The effect of 5 percent DA, 2.5 percent and 5.5 percent sodium hypochlorite, and saline on the solubility of organic matrix of the dentin was studied on extracted human teeth. The results showed that sodium hypochlorite dissolved collagen from the canal walls, while DA did not dissolve any collagen into the media. It is concluded that the root-canal-cleansing effect of DA is achieved by another mechanism, most likely by surface activity.

Chemical Phenomena↗