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Acta Tropica Mar 2023Pathogenic A. castellanii and N. fowleri are opportunistic free-living amoebae. Acanthamoeba spp. are the causative agents of granulomatous amebic encephalitis (GAE) and...
Pathogenic A. castellanii and N. fowleri are opportunistic free-living amoebae. Acanthamoeba spp. are the causative agents of granulomatous amebic encephalitis (GAE) and amebic keratitis (AK), whereas Naegleria fowleri causes a very rare but severe brain infection called primary amebic meningoencephalitis (PAM). Acridinone is an important heterocyclic scaffold and both synthetic and naturally occurring derivatives have shown various valuable biological properties. In the present study, ten synthetic Acridinone derivatives (I-X) were synthesized and assessed against both amoebae for anti-amoebic and cysticidal activities in vitro. In addition, excystation, encystation, cytotoxicity, host cell pathogenicity was also performed in-vitro. Furthermore, molecular docking studies of these compounds with three cathepsin B paralogous enzymes of N. fowleri were performed in order to predict the possible docking mode with pathogen. Compound VII showed potent anti-amoebic activity against A. castellanii with IC 53.46 µg/mL, while compound IX showed strong activity against N. fowleri in vitro with IC 72.41 µg/mL. Compounds II and VII showed a significant inhibition of phenotypic alteration of A. castellanii, while compound VIII significantly inhibited N. fowleri cysts. Cytotoxicity assessment showed that these compounds caused minimum damage to human keratinocyte cells (HaCaT cells) at 100 µg/mL, while also effectively reduced the cytopathogenicity of Acanthamoeba to HaCaT cells. Moreover, Cathepsin B protease was investigated in-silico as a new molecular therapeutic target for these compounds. All compounds showed potential interactions with the catalytic residues. These results showed that acridine-9(10H)-one derivatives, in particular compounds II, VII, VIII and IX hold promise in the development of therapeutic agents against these free-living amoebae.
Topics: Humans; Naegleria fowleri; Cathepsin B; Acridines; Molecular Docking Simulation; Acanthamoeba; Amoeba; Amebiasis; Brain
PubMed: 36610529
DOI: 10.1016/j.actatropica.2023.106824 -
Journal of Biochemical and Molecular... Oct 2022Developing new anticancer agents are crucial for cancer treatment. Antiproliferative activity of L1H as a bis-structured Schiff base was subjected to preliminary...
Developing new anticancer agents are crucial for cancer treatment. Antiproliferative activity of L1H as a bis-structured Schiff base was subjected to preliminary research in eight different kinds of cell lines by the cell viability method using different concentrations to determine their inhibitory concentration. L1H demonstrated the highest cytotoxicity in human breast cancer cell line MCF-7. In this perspective, the MCF-7 cell line was cultured for the examination of different molecular techniques, including MTT, apoptosis analysis by enzyme-linked immunosorbent assay (ELISA), and comet assay. Moreover, the DNA ladder, acridine orange/ethidium bromide as another apoptotic cell analysis, markers of oxidative stress, and total antioxidant status, total thiol, and GSH as nonenzymatic antioxidants assay were conducted. The above techniques have proven that L1H is a growth inhibitor effect when compared to cisplatin as a positive control in human breast cancer cells, especially those affected by L1H. The findings clearly show that L1H evaluated in MCF-7 cell lines causes rising or induced apoptosis, DNA damage, diminished antioxidant status against the increase of oxidized protein, and prevents cell proliferation. Manifold evidence supported our hypothesis that L1H has a potential therapeutically improved effect against the MCF-7 cell line, and then without a doubt is a suitable candidate drug for investigating cancers next.
Topics: Acridine Orange; Antineoplastic Agents; Antioxidants; Apoptosis; Breast Neoplasms; Cell Proliferation; Cisplatin; DNA; DNA Damage; Ethidium; Female; Growth Inhibitors; Humans; MCF-7 Cells; Schiff Bases; Sulfhydryl Compounds
PubMed: 35719061
DOI: 10.1002/jbt.23148 -
Chemical Record (New York, N.Y.) Jan 2021Herein we have reviewed our recent developments for the identification of new tacrine analogues for Alzheimer's disease (AD) therapy. Tacrine, the first cholinesterase... (Review)
Review
Herein we have reviewed our recent developments for the identification of new tacrine analogues for Alzheimer's disease (AD) therapy. Tacrine, the first cholinesterase inhibitor approved for AD treatment, did not stop the progression of AD, producing only some cognitive improvements, but exhibited secondary effects mainly due to its hepatotoxicity. Thus, the drug was withdrawn from the clinics administration. Since then, many publications have described non-hepatotoxic tacrines, and in addition, important efforts have been made to design multitarget tacrines by combining their cholinesterase inhibition profile with the modulation of other biological targets involved in AD.
Topics: Acetylcholinesterase; Alzheimer Disease; Cell Line, Tumor; Cholinesterase Inhibitors; Humans; Molecular Docking Simulation; Neuroprotective Agents; Protein Binding; Tacrine
PubMed: 33169934
DOI: 10.1002/tcr.202000107 -
The Journal of Physical Chemistry... Jun 2021An acridone derivative (-methyl-difluoro-acridone, NMA-dF) is characterized with respect to its utility as an emitter in organic light emitting diodes (OLEDs). Using...
An acridone derivative (-methyl-difluoro-acridone, NMA-dF) is characterized with respect to its utility as an emitter in organic light emitting diodes (OLEDs). Using steady-state and time-resolved spectroscopy as well as quantum chemistry, its ability to convert singlet and triplet excitons into light was scrutinized. NMA-dF emits in the deep blue range of the visible spectrum. Its fluorescence emission occurs with quantum yields close to 1 and a radiative rate constant of ≈5 × 10 s. So, it processes singlet excitons very efficiently. Using 1,4-dichlorobenzene as a sensitizer, it is shown that NMA-dF also converts triplet excitons into light. With the aid of quantum chemistry, this is related to a reverse intersystem crossing starting from a higher triplet state (HIGHrISC).
Topics: Acridones; Copper; Fluorescent Dyes
PubMed: 34125550
DOI: 10.1021/acs.jpclett.1c01381 -
Recent Patents on Anti-cancer Drug... 2022DNA topoisomerases are a class of enzymes that play a critical role in fundamental biological processes of replication, transcription, recombination, repair and...
BACKGROUND
DNA topoisomerases are a class of enzymes that play a critical role in fundamental biological processes of replication, transcription, recombination, repair and chromatin remodeling. Amsacrine (m-AMSA), the best-known compound of 9-anilinoacridines series, was one of the first DNA-intercalating agents to be considered a Topoisomerase II inhibitor.
OBJECTIVES
A series of sulfur-containing 9-anilinoacridines related to amsacrine were synthesized and evaluated for their anticancer activity.
METHODS
Cell viability was assessed by the MTT assay. The topoisomerase II inhibitory assay was performed using the Human topoisomerase II Assay kit, and flow cytometry was used to evaluate the effects on the cell cycle of K562 cells. Molecular docking was performed using the Schrödinger Maestro program.
RESULTS
Compound 36 was found to be the most cytotoxic of the sulfide series against SW620, K562, and MCF-7. The limited SAR suggested the importance of the methansulfonamidoacetamide side chain functionality, the lipophilicity, and the relative metabolic stability of 36 in contributing to the cytotoxicity. Topoisomerase II α inhibitory activity appeared to be involved in the cytotoxicity of 36 through the inhibition of decatenation of kinetoplast DNA (kDNA) in a concentration- dependent manner. Cell cycle analysis further showed Topo II inhibition through the accumulation of K562 cells in the G2/M phase of the cell cycle. The docking of 36 into the Topo II α-DNA complex suggested that it may be an allosteric inhibitor of Topo II α.
CONCLUSION
Compound 36 exhibits anticancer activity by inhibiting topoisomerase II, and it could further be evaluated in in vivo models.
Topics: Amsacrine; Antineoplastic Agents; DNA Topoisomerases, Type II; Humans; Molecular Docking Simulation; Sulfur; Topoisomerase II Inhibitors
PubMed: 34323200
DOI: 10.2174/1574892816666210728122910 -
Food & Function Feb 2021The effects of potato and traditional staple foods (corn, wheat and rice) on physiology and gut microbiota were investigated by feeding ICR mice for 12 months. Compared...
The effects of potato and traditional staple foods (corn, wheat and rice) on physiology and gut microbiota were investigated by feeding ICR mice for 12 months. Compared with traditional staple foods, potato significantly improved the food and water intake and survival rate, and inhibited the swelling of viscera of mice, accompanied by a decreased white blood cell count and urine bilirubin content. Furthermore, potato significantly increased the relative abundance of Bacteroides and Faecalibacterium, which are short-chain fatty acid producing bacteria and play very important roles in the maintenance of human health. Meanwhile, potato significantly decreased the relative abundance of spoilage bacteria Pseudomonas and Thiobacillus. Analysis of putative metagenomes indicated that the potato diet upregulated the gene abundance of glycan biosynthesis and metabolism, digestive system and immune system. These findings indicated that potato has the potential to be an excellent substitute for traditional staple foods owing to its good physiological function and favorable gut microbiota modulation.
Topics: Aminoacridines; Animal Feed; Animals; Bacteria; Body Weight; Diet; Drinking; Eating; Gastrointestinal Microbiome; Mice; Nitrogen Mustard Compounds; Oryza; Random Allocation; Solanum tuberosum; Triticum; Zea mays
PubMed: 33433545
DOI: 10.1039/d0fo02264k -
Nature Communications Nov 2021Chemoresistance posts a major hurdle for treatment of acute leukemia. There is increasing evidence that prolonged and intensive chemotherapy often fails to eradicate...
Chemoresistance posts a major hurdle for treatment of acute leukemia. There is increasing evidence that prolonged and intensive chemotherapy often fails to eradicate leukemic stem cells, which are protected by the bone marrow niche and can induce relapse. Thus, new therapeutic approaches to overcome chemoresistance are urgently needed. By conducting an ex vivo small molecule screen, here we have identified Quinacrine (QC) as a sensitizer for Cytarabine (AraC) in treating acute lymphoblastic leukemia (ALL). We show that QC enhances AraC-mediated killing of ALL cells, and subsequently abrogates AraC resistance both in vitro and in an ALL-xenograft model. However, while combo AraC+QC treatment prolongs the survival of primary transplanted recipients, the combination exhibits limited efficacy in secondary transplanted recipients, consistent with the survival of niche-protected leukemia stem cells. Introduction of Cdc42 Activity Specific Inhibitor, CASIN, enhances the eradication of ALL leukemia stem cells by AraC+QC and prolongs the survival of both primary and secondary transplanted recipients without affecting normal long-term human hematopoiesis. Together, our findings identify a small-molecule regimen that sensitizes AraC-mediated leukemia eradication and provide a potential therapeutic approach for better ALL treatment.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carbazoles; Cell Line, Tumor; Cytarabine; Drug Resistance, Neoplasm; Female; Humans; Male; Mice; Mice, Transgenic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Primary Cell Culture; Quinacrine; Xenograft Model Antitumor Assays
PubMed: 34836965
DOI: 10.1038/s41467-021-27300-w -
Animal Biotechnology Dec 2023Theileriosis is a hemoprotozoan illness of cattle in tropical regions that poses a severe economic loss to dairy farmers in the form of production loss and mortality. We...
Theileriosis is a hemoprotozoan illness of cattle in tropical regions that poses a severe economic loss to dairy farmers in the form of production loss and mortality. We designed and optimized a multiplex real-time PCR by using Taq-Man probe for detection and quantification of and simultaneously by targeting 18 s rRna and MPSP (surface merozoite protein) genes, respectively. Fifty-five EDTA blood samples from clinically -suspected cows of three -endemic districts of Odisha were processed using acridine dye based fluorescent microscopy, Giemsa staining, and PCR. PCR revealed and in 11/42 (26.11%) and 24/42 (57.14%) cases, respectively. Mixed infection due to both the spp. was recorded in 7/42 (16.66%). On comparison with gold standard test (PCR), the accuracy, sensitivity, and specificity were 92.72, 95.12, and 85.71% for Giemsa staining and 96.36, 97.56, and 92.85% for acridine orange dye. Multiplex real time PCR using Taq-Man probe detected two species of and simultaneously. Acridine dye based fluorescent microscopy is comparatively easy and rapid method in detection of spp.
Topics: Humans; Female; Cattle; Animals; Theileriasis; Theileria annulata; Cattle Diseases; RNA, Ribosomal; Membrane Proteins; Acridines
PubMed: 36695009
DOI: 10.1080/10495398.2023.2168197 -
Environmental Science and Pollution... Jun 2023In the current investigation, watermelon rinds (WMR) have been utilized as an eco-friendly and cost-efficient adsorbent for acridine orange (AO) from contaminated water...
In the current investigation, watermelon rinds (WMR) have been utilized as an eco-friendly and cost-efficient adsorbent for acridine orange (AO) from contaminated water samples. Adsorption of AO onto raw (RWM) and thermally treated rinds (TTWM250 and TTWM500) has been studied. The adsorption efficiency of the three adsorbents was evaluated by measuring the % removal (%R) of AO and the adsorption capacity (q, mg/g). Dependent variables (%R and q) were optimized as a function of four factors: pH, sorbent dosage (AD), the concentration of AO (DC), and contact time (ST). Box-Behnken (BB) design has been utilized to obtain the optimum adsorption conditions. Prepared adsorbents have been characterized using scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR), and Raman spectroscopies. The surface area of RWM, TTWM250, and TTWM500, as per the Brunauer-Emmett-Teller (BET) analysis, was 2.66, 2.93, and 5.03 m/g, respectively. Equilibrium investigations suggest that Freundlich model was perfectly fit for adsorption of AO onto TTWM500. Maximum adsorption capacity (q) of 69.44 mg/g was obtained using the Langmuir equation. Adsorption kinetics could be best described by the pseudo-second-order (PSO) model. The multi-cycle sorption-desorption study showed that TTWM500 could be regenerated with the adsorption efficiency being preserved up to 87% after six cycles.
Topics: Acridine Orange; Spectroscopy, Fourier Transform Infrared; Water Pollutants, Chemical; Kinetics; Adsorption
PubMed: 33829381
DOI: 10.1007/s11356-021-13652-9 -
Molecules (Basel, Switzerland) Nov 2022Proflavine is an acridine derivative which was discovered as one of the earliest antibacterial agents, and it has been proven to have potential application to fields...
Proflavine is an acridine derivative which was discovered as one of the earliest antibacterial agents, and it has been proven to have potential application to fields such as chemotherapy, photobiology and solar-energy conversion. In particular, it is well known that proflavine can bind to DNA with different modes, and this may open addition photochemical-reaction channels in DNA. Herein, the excited-state dynamics of proflavine after intercalation into DNA duplex is studied using femtosecond time-resolved spectroscopy, and compared with that in solution. It is demonstrated that both fluorescence and the triplet excited-state generation of proflavine were quenched after intercalation into DNA, due to ultrafast non-radiative channels. A static-quenching mechanism was identified for the proflavine-DNA complex, in line with the spectroscopy data, and the excited-state deactivation mechanism was proposed.
Topics: Proflavine; Intercalating Agents; DNA; Acridines
PubMed: 36500248
DOI: 10.3390/molecules27238157