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Current Opinion in Genetics &... Aug 2021The order Odonata (dragonflies and damselflies) comprises diurnal insects with well-developed vision, showing diverse colors in adult wings and bodies. It is one of the... (Review)
Review
The order Odonata (dragonflies and damselflies) comprises diurnal insects with well-developed vision, showing diverse colors in adult wings and bodies. It is one of the most ancestral winged insect groups. Because Odonata species use visual cues to recognize each other, color patterns have been investigated from ecological and evolutionary viewpoints. Here we review the recent progress on molecular mechanisms of pigmentation, especially focused on light-blue coloration. Results from histology and pigment analysis showed that ommochrome pigments on the proximal layer and pteridine pigments on the distal layer of the epidermis are essential for light-blue coloration. We also summarize genes involved in the biosynthesis of three major insect pigments conserved across insects and discuss that gene-functional analysis deserves future studies.
Topics: Animals; Color; Odonata; Phenothiazines; Phenotype; Pigmentation; Wings, Animal
PubMed: 33482606
DOI: 10.1016/j.gde.2020.12.014 -
Biointerphases Mar 2022Thin films of poly-d-lysine act as polar organic and are also light sensitive. The capacitance-voltage, current-voltage, and transistor behavior were studied to gauge...
Thin films of poly-d-lysine act as polar organic and are also light sensitive. The capacitance-voltage, current-voltage, and transistor behavior were studied to gauge the photoresponse of possible poly-d-lysine thin film devices both with and without methylene blue as an additive. Transistors fabricated from poly-d-lysine act as inverse phototransistors, i.e., the on-state current is greatest in the absence of illumination. The poly-d-lysine thin film capacitance and the transistor current decrease with illumination, both with and without methylene blue as an additive. This suggests that the unbinding of photo exciton is significantly hindered in this system which is supported by the significant charge carrier lifetime for poly-d-lysine films both with and without methylene blue. For the majority carrier, the transistor geometry appears to depend on the gate voltage; in other words, the majority carrier depends on the polarization of the poly-d-lysine films, both with and without methylene blue as an additive.
Topics: Lysine; Methylene Blue; Transistors, Electronic
PubMed: 35303768
DOI: 10.1116/6.0001692 -
Cell Apr 2020Protein phosphatase 2A (PP2A) enzymes can suppress tumors, but they are often inactivated in human cancers overexpressing inhibitory proteins. Here, we identify a class...
Protein phosphatase 2A (PP2A) enzymes can suppress tumors, but they are often inactivated in human cancers overexpressing inhibitory proteins. Here, we identify a class of small-molecule iHAPs (improved heterocyclic activators of PP2A) that kill leukemia cells by allosterically assembling a specific heterotrimeric PP2A holoenzyme consisting of PPP2R1A (scaffold), PPP2R5E (B56ε, regulatory), and PPP2CA (catalytic) subunits. One compound, iHAP1, activates this complex but does not inhibit dopamine receptor D2, a mediator of neurologic toxicity induced by perphenazine and related neuroleptics. The PP2A complex activated by iHAP1 dephosphorylates the MYBL2 transcription factor on Ser241, causing irreversible arrest of leukemia and other cancer cells in prometaphase. In contrast, SMAPs, a separate class of compounds, activate PP2A holoenzymes containing a different regulatory subunit, do not dephosphorylate MYBL2, and arrest tumor cells in G1 phase. Our findings demonstrate that small molecules can serve as allosteric switches to activate distinct PP2A complexes with unique substrates.
Topics: Apoptosis; Cell Cycle Proteins; Cell Line, Tumor; Enzyme Activators; G1 Phase; Humans; Multiprotein Complexes; Phenothiazines; Phosphorylation; Protein Phosphatase 2; Protein Subunits; Trans-Activators; Transcription Factors
PubMed: 32315619
DOI: 10.1016/j.cell.2020.03.051 -
Current Medicinal Chemistry 2021Molecules with a phenothiazine scaffold have been considered versatile organic structures with a wide variety of biological activities, such as antipsychotic,... (Review)
Review
BACKGROUND
Molecules with a phenothiazine scaffold have been considered versatile organic structures with a wide variety of biological activities, such as antipsychotic, anticancer, antibacterial, antifungal, antiviral, anti-inflammatory, antimalarial, and trypanocidal, etc. It was first discovered in the 19th century as a histochemical dye, phenothiazine methylene blue. Since then, its derivatives have been studied, showing new activities; moreover, they have also been repurposed.
OBJECTIVE
This review aims to describe the main synthetic routes of phenothiazines and, particularly, the anticancer and antiprotozoal activities reported during the second decade of the 2000s (2010 - 2020).
RESULTS
Several studies on phenothiazines against cancer and protozoa have revealed that these compounds show IC50 values in the micromolar and near nanomolar range. The structural analyses have revealed that compounds bearing halogens or electron-withdrawing groups at 2-position have favorable anticancer activity. Phenothiazine dyes have shown a photosensitizing activity against trypanosomatids at a micromolar range. Tetra and pentacyclic azaphenothiazines are structures with a high broad-spectrum anticancer activity.
CONCLUSION
The phenothiazine scaffold is favorable for developing anticancer agents, especially those bearing halogens and electron-withdrawing groups bound at 2-position with enhanced biological activities through a variety of aromatic, aliphatic and heterocyclic substituents in the thiazine nitrogen. Further studies are warranted along these investigation lines to attain more active anticancer and antiprotozoal compounds with minimal to negligible cytotoxicity.
Topics: Antineoplastic Agents; Antiprotozoal Agents; Antipsychotic Agents; Chemistry, Pharmaceutical; Humans; Phenothiazines; Structure-Activity Relationship
PubMed: 33820509
DOI: 10.2174/0929867328666210405120330 -
Viruses Jul 2023Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented...
Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence of new variants. Therefore, developing more effective and broad-spectrum therapeutic and prophylactic drugs against infection by SARS-CoV-2 and its variants, as well as future emerging CoVs, is urgently needed. In this study, we screened several US FDA-approved drugs and identified phenothiazine derivatives with the ability to potently inhibit the infection of pseudotyped SARS-CoV-2 and distinct variants of concern (VOCs), including B.1.617.2 (Delta) and currently circulating Omicron sublineages XBB and BQ.1.1, as well as pseudotyped SARS-CoV and MERS-CoV. Mechanistic studies suggested that phenothiazines predominantly inhibited SARS-CoV-2 pseudovirus (PsV) infection at the early stage and potentially bound to the spike (S) protein of SARS-CoV-2, which may prevent the proteolytic cleavage of the S protein, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that phenothiazines can serve as a potential broad-spectrum therapeutic drug for the treatment of SARS-CoV-2 infection as well as the infection of future emerging human coronaviruses (HCoVs).
Topics: Humans; SARS-CoV-2; Phenothiazines; COVID-19; Spike Glycoprotein, Coronavirus
PubMed: 37632009
DOI: 10.3390/v15081666 -
Molecules (Basel, Switzerland) Nov 2022Two unique structures were isolated from the phosphorylation reaction of 10-phenothiazine. The 5,5-dimethyl-2-(10-phenothiazin-10-yl)-1,3,2-dioxaphosphinane 2-oxide ()...
Two unique structures were isolated from the phosphorylation reaction of 10-phenothiazine. The 5,5-dimethyl-2-(10-phenothiazin-10-yl)-1,3,2-dioxaphosphinane 2-oxide () illustrates the product of -phosphorylation of phenothiazine. Moreover, a potential product of instability, a thiophosphoric acid , was successfully isolated and structurally characterized. Molecule , similarly to sulfoxide derivative , possesses interesting phosphorescence properties due to the presence of d-pπ bonds. The X-ray, NMR, and DFT computational studies indicate that compound exhibits an anomeric effect. Additionally, the syntheses of selected symmetrical and unsymmetrical pyridine-embedded phenazines were elaborated. To compare the influence of phosphorus and sulfur atoms on the structural characteristics of 10-phenothiazine derivatives, the high-quality crystals of (4a,12a-dihydro-12-benzo[5,6][1,4]thiazino[2,3-]quinoxalin-12-yl)(phenyl)methanone () and selected phenazines 5,12-diisopropyl-3,10-dimethyldipyrido[3,2-:3',2'-]phenazine () and 5-isopropyl-,3-trimethylpyrido[3,2-]phenazin-10-amine () were obtained. The structures of molecules , , 2-mercapto-5,5-dimethyl-1,3,2-dioxaphosphinane 2-oxide (), 3,7-dinitro-10-phenothiazine 5-oxide (), and were determined by single-crystal X-ray diffraction measurements.
Topics: Density Functional Theory; Phenothiazines; Magnetic Resonance Spectroscopy; Phenazines; Oxides
PubMed: 36364378
DOI: 10.3390/molecules27217519 -
Communications Biology Mar 2022Bacterial persister cells are temporarily tolerant to bactericidal antibiotics but are not necessarily dormant and may exhibit physiological activities leading to cell...
Bacterial persister cells are temporarily tolerant to bactericidal antibiotics but are not necessarily dormant and may exhibit physiological activities leading to cell damage. Based on the link between fluoroquinolone-mediated SOS responses and persister cell recovery, we screened chemicals that target fluoroquinolone persisters. Metabolic inhibitors (e.g., phenothiazines) combined with ofloxacin (OFX) perturbed persister levels in metabolically active cell populations. When metabolically stimulated, intrinsically tolerant stationary phase cells also became OFX-sensitive in the presence of phenothiazines. The effects of phenothiazines on cell metabolism and physiology are highly pleiotropic: at sublethal concentrations, phenothiazines reduce cellular metabolic, transcriptional, and translational activities; impair cell repair and recovery mechanisms; transiently perturb membrane integrity; and disrupt proton motive force by dissipating the proton concentration gradient across the cell membrane. Screening a subset of mutant strains lacking membrane-bound proteins revealed the pleiotropic effects of phenothiazines potentially rely on their ability to inhibit a wide range of critical metabolic proteins. Altogether, our study further highlights the complex roles of metabolism in persister cell formation, survival and recovery, and suggests metabolic inhibitors such as phenothiazines can be selectively detrimental to persister cells.
Topics: Anti-Bacterial Agents; Escherichia coli; Fluoroquinolones; Gram-Negative Bacteria; Phenothiazines
PubMed: 35264714
DOI: 10.1038/s42003-022-03172-8 -
Water Environment Research : a Research... Dec 2021The advent of global industrialization advancements has proven to be both a blessing and a curse for humanity, with significant detrimental consequences on marine... (Review)
Review
The advent of global industrialization advancements has proven to be both a blessing and a curse for humanity, with significant detrimental consequences on marine bodies, and methylene blue is one of the common offenders through textile industry runoffs. These dye runoffs are complex, neurotoxic, and carcinogenic and prevent sunlight from penetrating the water to hinder photosynthesis and increase the biological/biochemical oxygen demand (BOD), hence hampering the ontogenesis of photoautotrophic organisms and thus threatening marine life and causing an increase in unavailability and inaccessibility to healthy water for eco-fundamental networking. Traditional methods came into the limelight, but they are costly and inefficient. Amazingly, due to exceptional surface features, eco-friendliness, cost-effectiveness, catalytic efficiency, and antibacterial capabilities, biosynthesized nanoparticles emerged as a potential solution to these drawbacks encounter by the traditional approach. This review was based on a comprehensive review of publicly available literature (majorly 2019-2021 original research reports) using major scientific databases such as SciFinder, Scopus, PubMed, Google Scholar, and Science Direct. The keywords that were utilized to scoop up the scientific journals were as follows: dye degradation and decolorization, biosynthesis, methylene blue, silver nanoparticles, wastewater, and dye runoffs. Thus, this review highlights the green sources used for the bio-fabrication of silver nanoparticles, the current level of knowledge of biosynthesis mechanism, mechanism of degradation, and methylene blue dye degradation efficiency. PRACTITIONER POINTS: Bio-fabrication mechanism of green silver nano-architecture from plant, bacteria, fungi, and algae extract has been discussed. Various biological capping/reducing agents have been reported. Degradation efficiency of methylene blue dyes using silver nanoparticles has been discussed. Mechanism of degradation of methylene blue by green silver nanoparticles has been reported.
Topics: Catalysis; Metal Nanoparticles; Methylene Blue; Silver; Water
PubMed: 34595788
DOI: 10.1002/wer.1649 -
Journal of Photochemistry and... Sep 2022Fluorescence probes, as analytical tools with the ability to perform rapid and sensitive detection of target analytes, have made outstanding contributions to... (Review)
Review
Fluorescence probes, as analytical tools with the ability to perform rapid and sensitive detection of target analytes, have made outstanding contributions to environmental analysis and bioassays. Considering the expanding developments in these areas, fluorophores play a key role in the de-sign of fluorescence probes. Compared to classical fluorophores, phenothiazines with elec-tron-rich characteristics have been widely applied to construct electron donor-acceptor dyes, which exhibit outstanding performance in both fluorimetric and colorimetric analysis. In addition, these probes also exhibit the pronounced ability in both solution and solid-state, achieving portable detection for environmental analysis. In this review, we summarize recent advances in the performance of phenothiazine-based fluorescent probes for detecting various analytes, especially in cations, anions, ROS/RSS, enzyme and other small molecules. The general design rules, response mechanisms and practical applications of the probes are analyzed, followed by a discussion of exiting challenges and future research perspectives. It is hoped that this review will provide a few strategies for the development of phenothiazine-based fluorescent probes.
Topics: Fluorescent Dyes; Phenothiazines
PubMed: 35907277
DOI: 10.1016/j.jphotobiol.2022.112528 -
Anticancer Research Sep 2020Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research.
BACKGROUND/AIM
Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research.
MATERIALS AND METHODS
Three phenothiazines (promethazine, chlorpromazine and thioridazine) have been tested in combination with 11 active selenocompounds against MDR (ABCB1-overexpressing) mouse T-lymphoma cells to investigate their activity as combination chemotherapy and as antitumor adjuvants in vitro with a checkerboard combination assay.
RESULTS
Seven selenocompounds showed toxicity on mouse embryonic fibroblasts, while three showed selectivity towards tumor cells. Two compounds showed synergism with all tested phenothiazines in low concentration ranges (1.46-11.25 μM). Thioridazine was the most potent among the three phenothiazines.
CONCLUSION
Phenothiazines belonging to different generations showed different levels of adjuvant activities. All the tested phenothiazines are already approved medicines with known pharmacological and toxicity profiles, therefore, their use as adjuvants in cancer may be considered as a potential drug repurposing strategy.
Topics: ATP Binding Cassette Transporter, Subfamily B; Animals; Antineoplastic Agents; Cell Line, Tumor; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Lymphoma, T-Cell; Mice; Molecular Structure; Organoselenium Compounds; Phenothiazines
PubMed: 32878780
DOI: 10.21873/anticanres.14495