Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 44
Filter
1.
Eur J Med Chem ; 143: 1028-1038, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-29232580

ABSTRACT

In an attempt to develop effective and safe anticancer agents, we designed, synthesized and examined 23 novel quinacrine (QC) derivatives by combining the 9-aminoacridine scaffold and the [1,3]thiazinan-4-ones group. Most of these hybrids showed strong anticancer activities, among which 3-(3-(6-chloro-2-methoxyacridin-9-ylamino)propyl)-2-(thiophen-2-yl)-1,3-thiazinan-4-one (25; VR151) effectively killed many different cancer cell types, including eight breast cancer cell lines with different genetic background, two prostate cancer and two lung cancer cell lines. In contrast, compound 25 is less effective against non-cancer cells, suggesting it may be less toxic to humans. Our data showed that cancer cells are arrested in S phase for a prolonged period due to the down-regulation of DNA replication, leading to eventual cell death. We have also shown that the S phase arrest may be resulted by the down-regulation of cyclin A coupled with the continued up-regulation of cyclin E, which coincide with the down-regulation of mTor-S6K and mTor-4EBP1 pathways.


Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Drug Design , Quinacrine/analogs & derivatives , Thiazines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Humans , Molecular Structure , Quinacrine/chemical synthesis , Quinacrine/chemistry , Quinacrine/pharmacology , Structure-Activity Relationship , Thiazines/chemical synthesis , Thiazines/chemistry
2.
Eur J Pharm Sci ; 111: 215-225, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-28987536

ABSTRACT

The present study is based on the quantitative structure-activity relationship (QSAR) analysis of binding affinity toward human prion protein (huPrPC) of quinacrine, pyridine dicarbonitrile, diphenylthiazole and diphenyloxazole analogs applying different linear and non-linear chemometric regression techniques, including univariate linear regression, multiple linear regression, partial least squares regression and artificial neural networks. The QSAR analysis distinguished molecular lipophilicity as an important factor that contributes to the binding affinity. Principal component analysis was used in order to reveal similarities or dissimilarities among the studied compounds. The analysis of in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) parameters was conducted. The ranking of the studied analogs on the basis of their ADMET parameters was done applying the sum of ranking differences, as a relatively new chemometric method. The main aim of the study was to reveal the most important molecular features whose changes lead to the changes in the binding affinities of the studied compounds. Another point of view on the binding affinity of the most promising analogs was established by application of molecular docking analysis. The results of the molecular docking were proven to be in agreement with the experimental outcome.


Subject(s)
Prion Proteins/chemistry , Quinacrine/analogs & derivatives , Quinacrine/chemistry , Binding Sites , Computer Simulation , Humans , Models, Chemical , Models, Molecular , Molecular Structure , Protein Binding , Protein Conformation , Quantitative Structure-Activity Relationship
3.
ChemMedChem ; 11(24): 2703-2712, 2016 12 16.
Article in English | MEDLINE | ID: mdl-27863116

ABSTRACT

One of the earliest synthetic antimalarial drugs, quinacrine, was recently reported as interesting for the treatment of acute myeloid leukemia. Inspired by this and similar findings, we evaluated a set of quinacrine analogues against gastric (MKN-28), colon (Caco-2), and breast (MFC-7) cancer cell lines and one normal human fibroblast cell line (HFF-1). All the compounds, previously developed by us as dual-stage antimalarial leads, displayed antiproliferative activity, and one of the set stood out as selective toward the gastric cancer cell line, MKN-28. Interestingly, this compound was transported across an in vitro MKN-28 model cell line in low amounts, and approximately 80 % was trapped inside those cells. Nuclear targeting of the same compound and its interactions with calf thymus DNA were assessed through combined fluorescence microscopy, spectroscopy, and calorimetry studies, which provided evidence for the compound's ability to reach the nucleus and to interact with DNA.


Subject(s)
Quinacrine/analogs & derivatives , Quinacrine/pharmacology , Stomach Neoplasms , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , MCF-7 Cells , Microscopy, Fluorescence , Molecular Structure , Neoplasms/drug therapy , Quinacrine/chemistry , Quinacrine/therapeutic use , Stomach Neoplasms/drug therapy
4.
ChemMedChem ; 10(8): 1344-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26038181

ABSTRACT

In a follow-up study to our reports of N-cinnamoylated chloroquine and quinacrine analogues as promising dual-stage antimalarial leads with high in vitro potency against both blood-stage Plasmodium falciparum and liver-stage Plasmodium berghei, we decided to investigate the effect of replacing the cinnamoyl moiety with other acyl groups. Thus, a series of N-acylated analogues were synthesized, and their activities against blood- and liver-stage Plasmodium spp. were assessed along with their in vitro cytotoxicities. Although the new N-acylated analogues were found to be somewhat less active and more cytotoxic than their N-cinnamoylated counterparts, they equally displayed nanomolar activities in vitro against blood-stage drug-sensitive and drug-resistant P. falciparum, and significant in vitro liver-stage activity against P. berghei. Therefore, it is demonstrated that simple N-acylated surrogates of classical antimalarial drugs are promising dual-stage antimalarial leads.


Subject(s)
Antimalarials/chemistry , Cinnamates/chemistry , Antimalarials/chemical synthesis , Antimalarials/pharmacology , Cell Survival/drug effects , Chloroquine/analogs & derivatives , Chloroquine/chemical synthesis , Chloroquine/pharmacology , Hep G2 Cells , Humans , Life Cycle Stages/drug effects , Plasmodium berghei/drug effects , Plasmodium berghei/growth & development , Plasmodium falciparum/drug effects , Plasmodium falciparum/growth & development , Quinacrine/analogs & derivatives , Quinacrine/chemical synthesis , Quinacrine/pharmacology , Structure-Activity Relationship
5.
J Med Chem ; 58(7): 3025-35, 2015 Apr 09.
Article in English | MEDLINE | ID: mdl-25793774

ABSTRACT

Autophagy is a conserved cellular pathway used to recycle nutrients through lysosomal breakdown basally and under times of stress (e.g., nutrient deprivation, chemotherapeutic treatment). Oncogenes are known to induce autophagy, which may be exploited by cancers for cell survival. To identify autophagy inhibitors with potential therapeutic value for cancer, we screened a panel of antimalarial agents and found that quinacrine (QN) had 60-fold higher potency of autophagy inhibition than chloroquine (CQ), a well-known autophagy inhibitor that functions by disrupting lysosomal activity. Despite desirable autophagy inhibiting properties, QN showed considerable cytotoxicity. Therefore, we designed and synthesized a novel series of QN analogs and investigated their effects on autophagy inhibition and cell viability. Notably, we found two compounds (33 and 34), bearing a backbone of 1,2,3,4-tetrahydroacridine, had limited cytotoxicity yet strong autophagy inhibition properties. In conclusion, these improved lysomotropic autophagy inhibitors may have use as anticancer agents in combination with conventional therapies.


Subject(s)
Antineoplastic Agents/chemical synthesis , Autophagy/drug effects , Quinacrine/analogs & derivatives , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line/drug effects , Cell Survival/drug effects , Chemistry Techniques, Synthetic , Chloroquine/chemistry , Chloroquine/pharmacology , Drug Evaluation, Preclinical/methods , Humans , Lysosomes/drug effects , Microtubule-Associated Proteins/metabolism , Quinacrine/chemistry , Structure-Activity Relationship
6.
ChemMedChem ; 9(2): 305-10, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24474655

ABSTRACT

Plasmodium falciparum, the causative agent of the most lethal form of malaria, is becoming increasingly resistant to most available drugs. A convenient approach to combat parasite resistance is the development of analogues of classical antimalarial agents, appropriately modified in order to restore their relevance in antimalarial chemotherapy. Following this line of thought, the design, synthesis and in vitro evaluation of N-cinnamoylated quinacrine surrogates, 9-(N-cinnamoylaminobutyl)-amino-6-chloro-2-methoxyacridines, is reported. The compounds were found to be highly potent against both blood-stage P.falciparum, chloroquine-sensitive 3D7 (IC50 =17.0-39.0 nM) and chloroquine-resistant W2 and Dd2 strains (IC50 =3.2-41.2 and 27.1-131.0 nM, respectively), and liver-stage P.berghei (IC50 =1.6-4.9 µM) parasites. These findings bring new hope for the possible future "rise of a fallen angel" in antimalarial chemotherapy, with a potential resurgence of quinacrine-related compounds as dual-stage antimalarial leads.


Subject(s)
Antimalarials/chemistry , Antimalarials/pharmacology , Malaria/drug therapy , Plasmodium berghei/drug effects , Plasmodium falciparum/drug effects , Quinacrine/analogs & derivatives , Quinacrine/pharmacology , Cell Line , Chloroquine/pharmacology , Drug Design , Drug Resistance , Humans
8.
Eur J Med Chem ; 46(7): 2917-29, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21531054

ABSTRACT

In this paper, we report the synthesis and cell-based anti-prion activity of quinacrine analogs derived by replacing the basic alkyl side chain of quinacrine with 4-(4-methylpiperazin-I-yl)phenyl, (1-benzylpiperidin-4-yl) and their structural variants. Several promising analogs were found that have a more favorable anti-prion profile than quinacrine in terms of potency and activity across different prion-infected murine cell models. They also exhibited greater binding affinities for a human prion protein fragment (hPrP(121-231)) than quinacrine, and had permeabilities on the PAMPA-BBB assay that fall within the range of CNS permeant candidates. When evaluated on bidirectional assays on a Pgp overexpressing cell line, one analog was less susceptible to Pgp efflux activity compared to quinacrine. Taken together, the results point to an important role for the substituted 9-amino side chain attached to the acridine, tetrahydroacridine and quinoline scaffolds. The nature of this side chain influenced cell-based potency, PAMPA permeability and binding affinity to hPrP(121-231).


Subject(s)
Peptide Fragments/antagonists & inhibitors , Piperazines/chemistry , Piperidines/chemistry , Prions/antagonists & inhibitors , Quinacrine/analogs & derivatives , Quinacrine/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Animals , Binding Sites , Biological Transport , Blood-Brain Barrier/drug effects , Cell Line, Tumor , Dogs , Humans , Madin Darby Canine Kidney Cells , Mice , Peptide Fragments/chemistry , Permeability , Prion Diseases/drug therapy , Prion Diseases/metabolism , Prion Diseases/pathology , Prions/chemistry , Protein Binding , Protein Structure, Secondary , Protein Structure, Tertiary , Quinacrine/chemical synthesis , Recombinant Proteins/chemistry , Structure-Activity Relationship
9.
Neurotox Res ; 19(4): 556-74, 2011 May.
Article in English | MEDLINE | ID: mdl-20405353

ABSTRACT

Quinacrine is one of the few molecules tested to treat patients affected by prion diseases, although the clinical outcome is largely unsatisfactory. To identify novel derivatives with higher neuroprotective activity, we evaluated the effects of a small library of acridine derivatives. The 6-chloro-2-methoxyacridine derivatives bearing on position 9 a quinolizidin-1-ylamino (Q1, Q2) or a quinolizidin-1-ylalkylamino residue (Q3, Q4, Q6, Q7), the thio-bioisoster of Q3 (Q5), the 9-(N-lupinylthiopropyl)amino derivative (Q8) and simple acridines (Q9 and Q10) were considered. We compared the effects of quinacrine and these novel analogues in the inhibition of the cytotoxic activity and protease K (PK) resistance of the human prion protein fragment 90-231 (hPrP90-231). We demonstrate that quinacrine caused a significant reduction of hPrP90-231 toxicity due to its binding to the fragment and the prevention of its conversion in a toxic isoform. All acridine derivatives analyzed showed high affinity binding for hPrP90-231, but only Q3 and Q10, caused a significant reduction of hPrP90-231 cytotoxicity, with higher efficacy than quinacrine. We attempted to correlate the cytoprotective effects of the new compounds with some biochemical parameters (binding affinity to hPrP90-231, intrinsic fluorescence quenching, hydrophobic amino acid exposure), but a direct relationship occurred only with the reduction of PK resistance, likely due to the prevention of the acquisition of the ß-sheet-rich toxic conformation. These data represent interesting leads for further modifications of the basic side chain and the substituent pattern of the acridine nucleus to develop novel compounds with improved antiprion activity to be tested in in vivo experimental setting.


Subject(s)
Acridines/pharmacology , Peptide Fragments/antagonists & inhibitors , Peptide Fragments/toxicity , Prions/antagonists & inhibitors , Prions/toxicity , Quinacrine/pharmacology , Acridines/chemistry , Animals , Animals, Newborn , Cell Death/drug effects , Cell Death/physiology , Cell Line, Tumor , Cells, Cultured , Cerebellum/drug effects , Cerebellum/pathology , Humans , Quinacrine/analogs & derivatives , Rats , Rats, Sprague-Dawley , Treatment Outcome
10.
J Mol Model ; 17(2): 265-73, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20443037

ABSTRACT

Unique substrate specificity compared with ATP-dependent human DNA ligases recommends E.coli NAD(+)-ligases as potential targets. A plausible strategy is to identify the structural components of bacterial DNA ligase that interact with NAD(+) and then to isolate small molecules that recognize these components and thereby block the binding of NAD(+) to the ligase. This work describes a molecular modeling approach to detect the 3D structure of NAD(+)-dependent DNA ligase in E. coli whose partial structure was determined by wet lab experiments and rest structure was left as such on the road for repairment. We applied protein-drug docking approach to detect the binding affinity of this enzyme with Quinacrine and some of its virtual derivatives. In silico docking results predict that the virtual derivative of Quinacrine (C21H26ClN3O2) has greater binding affinity than Quinacrine. Drug likeness value of 0.833 was observed for this derivative without showing any toxicity risk.


Subject(s)
Anti-Bacterial Agents/metabolism , DNA Ligases/antagonists & inhibitors , DNA Ligases/metabolism , Drug Discovery , Escherichia coli/enzymology , NAD/metabolism , Quinacrine/analogs & derivatives , Amino Acid Sequence , Anti-Bacterial Agents/pharmacology , Binding Sites , DNA Ligases/chemistry , Escherichia coli/drug effects , Escherichia coli/genetics , Models, Molecular , Protein Binding , Protein Conformation , Quinacrine/metabolism , Quinacrine/pharmacology , Quinolines/metabolism , Quinolines/pharmacology , Sequence Analysis
11.
Chembiochem ; 9(6): 952-63, 2008 Apr 14.
Article in English | MEDLINE | ID: mdl-18330854

ABSTRACT

Amyloid formation and accumulation of the amyloid beta-peptide (Abeta) in the brain is associated with Alzheimer's disease (AD) pathogenesis. Therefore, among the therapeutic approaches in development to fight the disease, the direct inhibition of the Abeta self-assembly process is currently widely investigated and is one of the most promising approaches. In this study we investigated the potential of a multimeric display of quinacrine derivatives, as compared to the monomer quinacrine, as a design principal for a novel class of inhibitors against Abeta fibril formation. The presented multimeric conjugate exhibits a cluster of four quinacrine derivatives on a rigid cyclopeptidic scaffold. Herein is reported the synthesis of the conjugate, together with the in vitro inhibitory evaluation of Abeta(1-40) fibrils using the thioflavin T fluorescence assay, and imaging with atomic force microscopy. Our data show that the multimeric compound inhibits Abeta(1-40) fibril formation with an IC(50) value of 20+/-10 microM, which contrasts with the nonactive monomeric analogue. This work suggests that assembling multiple copies of acridine moieties to a central scaffold, for multiple interactions, is a promising strategy for the engineering of inhibitors against Abeta fibril formation.


Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/metabolism , Quinacrine/chemical synthesis , Quinacrine/pharmacology , Benzothiazoles , Dose-Response Relationship, Drug , Drug Design , Microscopy, Atomic Force , Protein Binding/drug effects , Quinacrine/analogs & derivatives , Quinacrine/chemistry , Spectrometry, Fluorescence , Thiazoles/chemistry
12.
J Med Chem ; 49(22): 6591-5, 2006 Nov 02.
Article in English | MEDLINE | ID: mdl-17064077

ABSTRACT

Human transmissible neurodegenerations including Creutzfeldt-Jakob disease are unique, since they are caused by prions, an infectious agent that replicates without nucleic acids but instead by inducing conversion of a host-resident normal prion protein to a misfolded conformational isoform. For pharmacotherapy of these unusual diseases, tricyclic heterocyclic compounds such as quinacrine have been considered, but with ambiguous success in vivo, so far. On the basis of the synergistic antiprion effects of quinacrine and iminodibenzyl derivatives, we introduce a novel class of potential pharmaceuticals representing structural chimeras of quinacrine and imipramine analogues. We describe the chemical synthesis and bioassays of a focused library of these compounds. The most potent target compound 2a revealed an EC(50) value of 20 nM determined with a cell model of prion disease, thus substantially improving the antiprion efficacy of quinacrine.


Subject(s)
Acridines/chemical synthesis , Acridines/pharmacology , Imipramine/analogs & derivatives , Imipramine/chemical synthesis , Prions/drug effects , Quinacrine/analogs & derivatives , Quinacrine/chemical synthesis , Animals , Blotting, Western , Cell Line, Tumor , Densitometry , Drug Design , Imipramine/pharmacology , Indicators and Reagents , Ligands , Mice , PrPSc Proteins/chemistry , PrPSc Proteins/drug effects , PrPSc Proteins/genetics , Quinacrine/pharmacology , Structure-Activity Relationship
13.
J Biol Chem ; 279(28): 29493-500, 2004 Jul 09.
Article in English | MEDLINE | ID: mdl-15102853

ABSTRACT

Trypanothione reductase is a key enzyme in the trypanothione-based redox metabolism of pathogenic trypanosomes. Because this system is absent in humans, being replaced with glutathione and glutathione reductase, it offers a target for selective inhibition. The rational design of potent inhibitors requires accurate structures of enzyme-inhibitor complexes, but this is lacking for trypanothione reductase. We therefore used quinacrine mustard, an alkylating derivative of the competitive inhibitor quinacrine, to probe the active site of this dimeric flavoprotein. Quinacrine mustard irreversibly inactivates Trypanosoma cruzi trypanothione reductase, but not human glutathione reductase, in a time-dependent manner with a stoichiometry of two inhibitors bound per monomer. The rate of inactivation is dependent upon the oxidation state of trypanothione reductase, with the NADPH-reduced form being inactivated significantly faster than the oxidized form. Inactivation is slowed by clomipramine and a melarsen oxide-trypanothione adduct (both are competitive inhibitors) but accelerated by quinacrine. The structure of the trypanothione reductase-quinacrine mustard adduct was determined to 2.7 A, revealing two molecules of inhibitor bound in the trypanothione-binding site. The acridine moieties interact with each other through pi-stacking effects, and one acridine interacts in a similar fashion with a tryptophan residue. These interactions provide a molecular explanation for the differing effects of clomipramine and quinacrine on inactivation by quinacrine mustard. Synergism with quinacrine occurs as a result of these planar acridines being able to stack together in the active site cleft, thereby gaining an increased number of binding interactions, whereas antagonism occurs with nonplanar molecules, such as clomipramine, where stacking is not possible.


Subject(s)
Drug Design , Enzyme Inhibitors/metabolism , NADH, NADPH Oxidoreductases/chemistry , NADH, NADPH Oxidoreductases/metabolism , Quinacrine Mustard/metabolism , Quinacrine/analogs & derivatives , Animals , Binding Sites , Clomipramine , Enzyme Inhibitors/chemistry , Glutathione Reductase/chemistry , Glutathione Reductase/genetics , Glutathione Reductase/metabolism , Humans , Models, Molecular , Molecular Structure , NADH, NADPH Oxidoreductases/antagonists & inhibitors , NADH, NADPH Oxidoreductases/genetics , Oxidation-Reduction , Quinacrine/metabolism , Trypanosoma cruzi/enzymology
15.
Bioorg Med Chem Lett ; 11(19): 2655-7, 2001 Oct 08.
Article in English | MEDLINE | ID: mdl-11551771

ABSTRACT

Sulfonamide and urea derivatives of quinacrine with varying methylene spacer lengths were synthesised and tested for inhibition of trypanothione reductase (TryR) and for activity in vitro against strains of the parasitic protozoa Trypanosoma, Leishmania, and Plasmodium. These derivatives are superior inhibitors of TryR relative to quinacrine with the best compound being 40 times more potent. Urea derivatives generally displayed good in vitro activity against all parasites.


Subject(s)
Antiprotozoal Agents/pharmacology , Quinacrine/pharmacology , Sulfonamides/chemistry , Trypanosoma/drug effects , Urea/chemistry , Animals , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/chemistry , Leishmania/drug effects , Parasitic Sensitivity Tests , Plasmodium/drug effects , Quinacrine/analogs & derivatives , Quinacrine/chemical synthesis , Quinacrine/chemistry
16.
Nucleic Acids Symp Ser ; (44): 235-6, 2000.
Article in English | MEDLINE | ID: mdl-12903355

ABSTRACT

The solution structures of 1:1 complexes of a quinacrine-netropsin hybrid molecule with the self-complementary DNA duplexes, d(CGCGAATTCGCG)2 and d(CGAATTCG)2, have been studied by one- and two-dimensional 1H NMR spectroscopy. The NOE data indicate that the acridine ring of the hybrid intercalates into the 5'-GpA step and its netropsin moiety spans the minor groove of the central AATT region.


Subject(s)
DNA/chemistry , Intercalating Agents/chemistry , Netropsin/analogs & derivatives , Quinacrine/analogs & derivatives , Base Sequence , Molecular Structure , Netropsin/chemistry , Nuclear Magnetic Resonance, Biomolecular , Oligodeoxyribonucleotides/chemistry , Protons , Quinacrine/chemistry , Solutions
17.
Nucleic Acids Symp Ser ; (29): 87-8, 1993.
Article in English | MEDLINE | ID: mdl-8247806

ABSTRACT

The interaction of DNA with quinacrine and its analogs has been studied by absorption and circular dichroism (CD) spectroscopy. The results indicate that the 2-alkoxy group of the acridine ring plays an important role in the spectral behavior which depends on the base composition of DNA.


Subject(s)
DNA, Bacterial/chemistry , DNA/chemistry , Quinacrine/chemistry , Animals , Cattle , Circular Dichroism , Quinacrine/analogs & derivatives , Spectrum Analysis
18.
Nucleic Acids Symp Ser ; (27): 59-60, 1992.
Article in English | MEDLINE | ID: mdl-1283915

ABSTRACT

Temperature-jump relaxation method has been used to study the interaction of synthetic RNAs with quinacrine (QAC) and its analog. Two relaxation times were observed. The dependence of relaxation times on the RNA concentration and optical properties of the RNA-dye complexes suggests that (1) QAC binds to poly-(rA).poly(rU) through two bimolecular reactions including isomerization from one complex form to another and (2) the 2-methoxy group of the acridine ring plays a significant role in the isomerization.


Subject(s)
Quinacrine/chemistry , RNA/chemistry , Kinetics , Poly A-U/chemistry , Poly I-C/chemistry , Quinacrine/analogs & derivatives , RNA/chemical synthesis , Temperature
19.
Nucleic Acids Symp Ser ; (27): 75-6, 1992.
Article in English | MEDLINE | ID: mdl-1283918

ABSTRACT

The interaction of synthetic RNAs with quinacrine (QAC) and its analogs has been studied by absorption, fluorescence and circular dichroism (CD) measurements. The results indicate that the 2-methoxy group of the acridine ring plays an important role in the appearance of the new absorption band upon binding of QAC to poly-(rA).poly(rU).


Subject(s)
Quinacrine/chemistry , RNA/chemistry , Molecular Structure , Poly A-U/chemistry , Poly I-C/chemistry , Quinacrine/analogs & derivatives , Spectrum Analysis
20.
Jikken Dobutsu ; 38(3): 263-7, 1989 Jul.
Article in Japanese | MEDLINE | ID: mdl-2477262

ABSTRACT

The fluorescent body (F-body) was identified with quinacrine mustard (Q-M) staining in spermatozoon and lymphocyte of canine. Well washed sperm suspension was treated with protease (125 mg/ml) or dispase (2000p. u./ml) and staining with Q-M (final dilution 50 micrograms/ml) for 15 min to 24 hr at 37 degrees C. The lymphocyte cultures from whole blood were prepared as routine human investigation. The chromosomal preparation made by air dry method was stained with Q-M (final dilution 0.5 to 50 micrograms/ml) after pretreatment of enzyme digestion. The examination using a reflected fluorescent microscope revealed that the same F-body in human was present in both spermatozoon (20.1-39.7%) and interphase of lymphocyte (0.37.2%) of male origin.


Subject(s)
Lymphocytes/cytology , Quinacrine Mustard , Quinacrine , Spermatozoa/cytology , Y Chromosome/analysis , Animals , Dogs , Female , Fluorescence , Interphase , Male , Quinacrine/analogs & derivatives , Staining and Labeling
SELECTION OF CITATIONS
SEARCH DETAIL
...