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Search results for: telomerase inhibitors
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Teloxantron inhibits the processivity of telomerase with preferential DNA damage on telomeres
PublicationTelomerase reactivation is one of the hallmarks of cancer, which plays an important role in cellular immortalization and the development and progression of the tumor. Chemical telomerase inhibitors have been shown to trigger replicative senescence and apoptotic cell death both in vitro and in vivo. Due to its upregulation in various cancers, telomerase is considered a potential target in cancer therapy. In this study, we identified...
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Telomere and Telomerase
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In silico design of telomerase inhibitors.
PublicationTelomerase is a reverse transcriptase enzyme involved in DNA synthesis at the end of linear chromosomes. Unlike in most other cells, telomerase is reactivated most cancerous cells and, therefore, has become a promising new anticancer target. Despite extensive research, direct telomerase inhibitors have yet not been introduced to the clinics because of the complexity of this enzyme. Structures of this protein from simple organisms...
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Molecular modeling and evaluation of novel dibenzopyrrole derivatives as telomerase inhibitors and potential drug for cancer therapy
PublicationDuring previous years, many studies on synthesis, as well as on anti-tumor, anti-inflammatory and anti-bacterial activities of the pyrazole derivatives have been described. Certain pyrazole derivatives exhibit important pharmacological activities and have proved to be useful template in drug research. Considering importance of pyrazole template, in current work the series of novel inhibitors were designed by replacing central...
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Inhibitors of Matriptase‐2 Based on the Trypsin Inhibitor SFTI‐1
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Inhibitory mikrotubul w terapii przeciwnowotworowej = Inhibitors of microtubule in cancer therapy
PublicationW artykule opisano inhibitory mikrotubul, różnorodne związki chemiczne, znajdujące się w zaawansowanych przedklinicznych i wstępnych badaniach klinicznych. Pośród nich na uwagę zasługują półsyntetyczne analogi taksolu, substancje pochodzenia naturalnego, takie jak: epotilony, kombretastatyny, kolchinoidy, dolastatyny oraz syntetyczne związki o niskim ciężarze czasteczkowym: heterokombretastatyny, sulfonamidy, fenostatyny, pochodne...
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Design of serine proteinase inhibitors by combinatorial chemistry using trypsin inhibitor SFTI‐1 as a starting structure
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Structural, functional, and stability change predictions in human telomerase upon specific point mutations,
PublicationOverexpression of telomerase is one of the hallmarks of human cancer. Telomerase is important for maintaining the integrity of the ends of chromosomes, which are called telomeres. A growing number of human disease syndromes are associated with organ failure caused by mutations in telomerase (hTERT or hTR). Mutations in telomerase lead to telomere shortening by decreasing the stability of the telomerase complex, reducing its accumulation,...
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Structural analysis and predicting effects of natural mutations on telomerase
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Telomerase inhibition - unfulfilled hopes in the perfect molecular target
PublicationTelomerase plays a pivotal role in cell proliferation, homeostasis, and neoplastic transformation, making it a promising molecular target for cancer chemotherapy. Of note, although hTERT has been explored thoroughly as a target, none of the promising molecules has been approved as a drug until now. The subject of research conducted as part of my doctoral dissertation is explaining the cellular and molecular mechanism of action...
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Inhibitory activity of double‐sequence analogues of trypsin inhibitor SFTI‐1 from sunflower seeds: an example of peptide splicing
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Truncation of Huia versabilis Bowman-Birk inhibitor increases its selectivity, matriptase-1 inhibitory activity and proteolytic stability
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Introduction of Pro and Its Analogues in the Conserved P1 Position of Trypsin Inhibitor SFTI-1 Retains Its Inhibitory Activity
PublicationA number of monocyclic SFTI-1 analogues modified in the conserved inhibitor P1 position by Pro, its L-hydroxyproline (Hyp) derivative as well as mimetics with different ring size were synthesized by the solid-phase method. Replacement of Ser6 by Pro, Hyp, and a four-member ring, L-azetidine-2-carboxylic acid (Aze), retained trypsin or chymotrypsin inhibitory activity. The determined association equilibrium constants of these analogues...
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Selection of peptomeric inhibitors of bovine α-chymotrypsin and cathepsin G based on trypsin inhibitor SFTI-1 using a combinatorial chemistry approach
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Telomeraza jako cel terapii przeciwnowotworowej
PublicationTelomeraza jako cel terapii przeciwnowotworowej
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Effect Of Resveratrol And Quercetin On Telomerase Regulation In Cancer Cells And Their Anti-Cancer Potential
PublicationTelomeres and telomerase are nowadays one on targets for anticancer therapy. Telomerase is expressed in ~90% of human cancer cell lines and tumor specimens, whereas its enzymatic activity is not detectable in most human somatic cells. Was found that some dietary compounds can modulate telomerase activity in cancer cells. This review summarizes the current knowledge about the effects of resveratrol and quercetin on telomerase regulation...
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Analogues of trypsin inhibitor SFTI-1 modified in the conserved P1′ position by synthetic or non-proteinogenic amino acids retain their inhibitory activity
PublicationA series of linear and monocyclic (with a disulfide bridge only) analogues of trypsin inhibitor SFTI-1 modified in the P-1 and/or P-1' positions were synthesized by the solid-phase method. In the substrate specificity P-1 position, Phe or N-benzylglycine (Nphe) were introduced, whereas the conserved Ser6 in Bownam-Birk (BBI) inhibitors was replaced by Hse (L-homoserine), Nhse [N-(2-hydroxyethyl)glycine], Sar, and Ala. Kinetic studies...
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Biologically active compounds based on the carbazole scaffold - synthetic and mechanistic aspects
PublicationDoctoral dissertation is divided into three main parts: introduction, results and discussion and experimental. The introduction is divided into four main parts which describe: 5-hydroxytryptamine receptors, the most popular antidepressants, new compounds based on the carbazole structure with affinity for serotonin receptors, telomeres and telomerase with their functions, telomerase inhibition strategies, carbazoles approved in...
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Introduction of non-natural amino acid residues into the substrate-specific P1 position of trypsin inhibitor SFTI-1 yields potent chymotrypsin and cathepsin G inhibitors
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Proteinase 3 phosphonic inhibitors
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Neuroprotective Effect of SGLT2 Inhibitors
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Flavonoids as inhibitors of human neutrophil elastase
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Clays as Inhibitors of Polyurethane Foams’ Flammability
PublicationPolyurethanes are a very important group of polymers with an extensive range of applications in different branches of industry. In the form of foams, they are mainly used in bedding, furniture, building, construction, and automotive sectors. Due to human safety reasons, these applications require an appropriate level of flame retardance, often required by various law regulations. Nevertheless, without the proper modifications,...
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Catalytic topoisomerase II inhibitors in cancer therapy.
PublicationDNA topoizomeraza II jest jednym z głównych celów molekularnych dla leków stosowanych w terapii przeciwnowotworowej. Wszystkie inhibitory tego enzymu są zdolne do zakłócania w jeden z etapów cyklu katalitycznego topoizomerazy II. Związki, które stabilizują kowalencyjny kompleks DNa i topoizomerazy II (znany jako kompleks rozszczepialny) są nazywane truciznami topoizomerazy, inne związki, które hamują aktywność enzymu na innych...
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New potent cathepsin G phosphonate inhibitors
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ACEI and ARB — Each Unique RAAS Inhibitors
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COMPUTER-AIDED DESIGN OF ORGANOPHOSPHORUS INHIBITORS OF UREASE
PublicationBased on the structure of the most potential inhibitor diamidophosphate, various novel groups of inhibitors were developed by knowledge-based design approach with covalent carbon-phosphorus or carbon-phosphorus-carbon bond to improve hydrolytic stability to inhibit the microbial ureases. Designed compounds were evaluated with 10 (LigScore1, LigScore2, PLP1, PLP2, JAIN, PMF, PMF04, LUDI_1, LUDI_2 and LUDI_3) different scoring functions...
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Inhibitors of amino acids biosynthesis as antifungal agents
PublicationFungal microorganisms, including the human pathogenic yeast and filamentous fungi, are able to synthesize all proteinogenic amino acids, including nine that are essential for humans. A number of enzymes catalyzing particular steps of human-essential amino acid biosynthesis are fungi specific. Numerous studies have shown that auxotrophic mutants of human pathogenic fungi impaired in biosynthesis of particular amino acids exhibit...
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HDAC Inhibitors: Innovative Strategies for Their Design and Applications
PublicationHistone deacetylases (HDACs) are a large family of epigenetic metalloenzymes that are involved in gene transcription and regulation, cell proliferation, differentiation, migration, and death, as well as angiogenesis. Particularly, disorders of the HDACs expression are linked to the development of many types of cancer and neurodegenerative diseases, making them interesting molecular targets for the design of new efficient drugs...
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Therapeutic Potential of Multifunctional Derivatives of Cholinesterase Inhibitors
PublicationThe aim of this work is review of tacrine analogues from the last three years, which were not included in the latest review work, donepezil and galantamine hybrids from 2015 and rivastigmine derivatives from 2014. In this account we summarize the efforts toward the development and characterization of non-toxic inhibitors of cholinesterases based on mentioned drugs with various interesting additional properties such as antioxidant,...
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TRF1 and TRF2: pioneering targets in telomere-based cancer therapy
PublicationThis article presents an in-depth exploration of the roles of Telomere Repeat-binding Factors 1 and 2 (TRF1 and TRF2), and the shelterin complex, in the context of cancer biology. It emphasizes their emerging significance as potential biomarkers and targets for therapeutic intervention. Central to the shelterin complex, TRF1 and TRF2 are crucial in maintaining telomere integrity and genomic stability, their dysregulation often...
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Moderate-to-severe obstructive sleep apnea is associated with telomere lengthening
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Minimum inhibitory concentrations (MICs) determination of selected human topoisomerase II alpha and bacterial DNA gyrase inhibitors against fungal strains
Open Research DataThe datasets contain the results of determining the MIC (Minimal Inhibitory Concentration) value of known compounds* (inhibitors of human topoisomerase II alpha and bacterial DNA gyrase) against C. albicans SC5314, C. glabrata ATCC 90030, C. krusei ATCC 6258 and C. parapsilosis ATCC 22019 and Saccharomyces cerevisiae ATCC 9763 by the modified M27-A3...
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Synthesis of the inosine 5′-monophosphate dehydrogenase (IMPDH) inhibitors
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Synthesis of anthraquinone-tuftsin analogues as potential topoisomerase inhibitors
PublicationZaprezentowano syntezę nowych analogów antrachinonów z pochodnymi tuftsyny i retro-tuftsyny oraz wstępne badania biologiczne (aktywność cytotoksyczną na wybranych liniach nowotworowych oraz zdolność hamowania topoizomerazy I).
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An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure
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Low-Molecular-Weight Aldehyde Inhibitors of Cathepsin G
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Inhibitors of cathepsin G: a patent review (2005 to present)
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Direct renin inhibitors in hypertension – Approaching the moment of truth
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CDK9 inhibitors in multiple myeloma: a review of progress and perspectives
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Cyclic Peptidic Furin Inhibitors Developed by Combinatorial Chemistry
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Inhibitors of angiogenesis in cancer therapy – synthesis and biological activity
PublicationAngiogenesis is the process of formation of new capillaries from preexisting blood vessels. Angiogenesis is involved in normal physiological processes, and plays an important role in tumor invasion and development of metastases. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis. VEGF is a mitogen for vascular endothelial cells and stimulates their proliferation. By inhibiting the biological activity of...
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Synthesis of the inosine 5'-monophosphate dehydrogenase (IMPDH) inhibitors
PublicationIn this review are summrized newly described IMPDH inhibitors. The article concerns both synthetic pathways and biological activities of the most promising compounds.
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Phosphate and Thiophosphate Biphenyl Analogs as Steroid Sulfatase Inhibitors
PublicationIn the present work, we report convenient methods for the synthesis and biological evaluation of phosphate and thiophosphate biphenyl derivatives exhibiting steroid sulfatase (STS) activity. The described synthesis is based on straightforward preparation of biphenyl-4-ol and 40-hydroxybiphenyl- 4-carboxylic acid ethyl ester modified with various phosphate or thiophosphate moieties. The inhibitory effects of these compounds were...
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Synthesis of bicoumarin thiophosphate derivatives as steroid sulfatase inhibitors
PublicationBased on the frameworks of 7-hydroxy-2,3-dihydro-1H-cyclopenta[c]chromen-4-one, 3-hydroxy- 7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one and 3-hydroxy-8,9,10,11-tetrahydro-7H-cyclohepta[c] chromen-6-one, a series of bicoumarin thiophosphate analogs have been synthesized and biologically evaluated. Additionally, their binding modes have been modeled using docking techniques. The inhibitory properties of the synthesized compounds...
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Distance between the Basic Group of the Amino Acid Residue's Side Chain in Position P1of Trypsin Inhibitor CMTI-III and Asp189in the Substrate Pocket of Trypsin Has an Essential Influence on the Inhibitory Activity
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Metylotransferazy ssaków – inhibitory i aktywatory
PublicationWśród metylotransferaz ssaków możemy wyróżnić metylotransferazy histonowe oraz metylotransferazy DNA. Metylacja DNA w obrębie wysp CpG oraz metylacja histonów wpływają na poziom ekspresji genów w komórkach ssaczych. Dodatkowo dzięki metylacji zapewniana jest stabilność i integralność genomu ludzkiego. Metylotransferazy DNA, będące głównym tematem tego artykułu, są często przedmiotem badań, gdyż nieprawidłowa metylacja DNA jest...
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The effect of anthraquinone derivatives on telomerase activity
Open Research DataThe data set contains images of the PCR products obtained from the Telomerase Repeated Amplification Protocol (TRAP). The effect of anthraquinone derivatives (TXT1-TXT9) on telomerase activity was comparatively examined using the following reference compounds: BIBR1532, TMPyP4 and mitoxantrone (MTX).
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Biotransformation of Modified Benzylisoquinoline Alkaloids: Boldine and Berberine and In Silico Molecular Docking Studies of Metabolites on Telomerase and Human Protein Tyrosine Phosphatase 1B
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Inhibitors of glucosamine-6-phosphate synthase as potential antifungal drugs.
PublicationPrzedstawiono stan obecny i perspektywy zastosowania inhibitorów enzymu syntazy GlcN-6-P jako leków skutecznych w leczeniu grzybic układowych. Używając metod modelowania molekularnego zaprojektowano struktury inhibitorów enzymu należących do dwóch grup strukturalnych: analogów glutaminy oraz analogów stanu przejściowego reakcji katalizowanej przez enzym. Opracowano metody syntezy pochodnych zoptymalizowanych inhibitorów, wykazujących...