Disease relevance of Labosept

• Photo-induced inactivation of protein kinase calpha by dequalinium inhibits motility of murine melanoma cells [1].
• Overexpression of TehAB results in hypersensitivity to dequalinium CI and methyl viologen (paraquat) [2].
• At 1 microM, dequalinium produced non-surmountable antagonism of the ganglion depolarization evoked by nicotinic receptor activation [3].
• Toxicity of the mitochondrial poison dequalinium chloride in a murine model system [4].
• After the development of a reproducible murine intraperitoneal (ip) human ovarian cancer model, which maintained the biologic characteristics of the parent cell line, we undertook in vivo evaluation of DECA [5].

High impact information on Labosept

• Dequalinium has previously been shown to be an anticarcinoma agent (M. J. Weiss et al., Proc. Natl. Acad. Sci. USA, 84: 5444-5448, 1987) [6].
• Dequalinium belongs to a group of cationic lipophilic drugs believed to be selectively cytotoxic to malignant cells of epithelial origin by virtue of their accumulation in mitochondria [7].
• We found that multidrug-resistant lines were less sensitive than parental cell lines to the intrinsic growth inhibitory effects of dequalinium (IC50, 4.4 versus 0.3 microM in multidrug-resistant and sensitive P388 cells, respectively), whereas they were equally sensitive as the parental line to the effects of trifluoperazine [7].
• Studies conducted with types I, II, and III rat brain isozymes, resolved by hydroxylapatite chromatography, demonstrate that dequalinium inhibits each of them with similar potency (50% inhibitory concentration of 11 microM) and imply that the site of contact on the enzyme is a highly conserved region [6].
• Related studies show that the analogues display the same rank order of inhibitory potency when tested with the trypsin-generated catalytic fragment of the enzyme, indicating that dequalinium inhibits kinase activity through an interaction with the catalytic subunit [6].

Chemical compound and disease context of Labosept

• 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 [8].

Biological context of Labosept

• In addition, dequalinium treatment of the alpha-synuclein-overexpressing cells exerted a significant cell death [9].
• Treatment of cultured human cervical carcinoma cells with the anticancer drug dequalinium (DEQ) was found to cause a delayed inhibition of cell growth [10].
• Our data also demonstrate that dequalinium interacts with the permeant ion probably because it occupies a binding site in the ion conducting pathway [11].
• Synthesis and quantitative structure-activity relationship of a novel series of small conductance Ca(2+)-activated K+ channel blockers related to dequalinium [12].
• Synthesis and structure-activity relationships of dequalinium analogues as K+ channel blockers. Investigations on the role of the charged heterocycle [13].

Anatomical context of Labosept

• The trypanocidal drug crystal violet, as well as other cationic drugs such as dequalinium, induced a rapid dose-related collapse of the inner mitochondrial membrane potential [14].
• Affinity labeling was abolished on both liver and brain membranes by apamin, scyllatoxin, dequalinium, gallamine, and d-tubocurarine [15].
• When applied to the intracellular side of inside-out excised patches from Xenopus oocytes, dequalinium blocks CNGA1 channels with a K(1/2) approximately 190 nM and CNGA1+CNGB1 channels with a K(1/2) approximately 385 nM, at 0 mV [11].
• 7. Direct activation of SKCa channels by raising cytosolic Ca2+ in hepatocytes evoked an outward current which was reduced by the three blockers, with dequalinium being the most potent [16].
• 1. Nine bis-quinolinyl and bis-quinolinium compounds related to dequalinium, and previously shown to block apamin-sensitive small conductance Ca(2+)-activated K(+) channels (SK(Ca)), have been tested for their inhibitory effects on actions mediated by intermediate conductance Ca(2+)-activated K(+) channels (IK(Ca)) in rabbit blood cells [17].

Associations of Labosept with other chemical compounds

• In contrast to the F1-ATPases from bovine mitochondria and the thermophilic Bacillus PS3, which are reversibly inhibited by dequalinium in the absence of irradiation, the Mg2+-ATPase activity of heat- or dithiothreitol-activated chloroplast F1 (CF1) from spinach chloroplasts is slightly stimulated by dequalinium [18].
• Lipophilic cationic compounds such as rhodamine 123, AA1, and dequalinium chloride have been reported to constitute a new class of anticarcinoma agents based on their selective localization, accumulation, and retention within the mitochondria of certain carcinoma cells [19].
• Human cultured cell lines transfected with SK2 yielded Ca(2+)-sensitive K+ current that was blocked by dequalinium chloride and apamin, known blockers of SK channels [20].
• Suramin prevents cerebellar granule cell-death induced by dequalinium [21].
• Hyperpolarizing and depolarizing responses to muscarine recorded extracellularly from frog ganglia were antagonized by 3 microM dequalinium [3].

Gene context of Labosept

• Dequalinium has recently been reported to block CNGA1 and CNGA2 channels expressed in Xenopus laevis [22].
• Peptide toxins such as apamin and scyllatoxin, as well as organic compounds such as quaternary salts of bicuculline, dequalinium, UCL 1684 and UCL 1848 serve as non-specific SK channel blockers [23].
• Photoinduced inactivation of protein kinase C by dequalinium identifies the RACK-1-binding domain as a recognition site [24].
• We previously noted that dequalinium is a high-affinity blocker of CNGA1 channels from the intracellular side, with little or no state dependence at 0 mV [25].
• Therefore, it is pertinent to consider that dequalinium could be used as a molecular probe to assess toxic mechanisms related to the amyloid formation of alpha-synuclein [9].

Analytical, diagnostic and therapeutic context of Labosept

• The protein was self-oligomerized by dequalinium, which gave rise to the ladder formation on N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine/SDS-PAGE in the presence of a coupling reagent of N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline [9].
• Inhibition of rat colon tumor isograft growth with dequalinium chloride [26].
• After density gradient centrifugation a band of dequalinium (DQA) tightly associated with DNA is located between the DNA and DQA bands [27].
• Determination of the quaternary ammonium compounds dequalinium and cetylpyridinium chlorides in candy-based lozenges by high-performance liquid chromatography [28].
• Comparative in vitro evaluation of dequalinium B, a new boron carrier for neutron capture therapy (NCT) [29].

References