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Search results for: MEDICINAL CHEMISTRY
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Exploiting the S4–S5 Specificity of Human Neutrophil Proteinase 3 to Improve the Potency of Peptidyl Di(chlorophenyl)-phosphonate Ester Inhibitors: A Kinetic and Molecular Modeling Analysis
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Peptomeric analogues of trypsin inhibitor SFTI-1 isolated from sunflower seeds
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Substrate specificity and inhibitory study of human airway trypsin-like protease
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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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New potent cathepsin G phosphonate inhibitors
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Rational design, synthesis and biological evaluation of thiadiazinoacridines: a new class of antitumor agents.
PublicationZsyntetyzowano serię związków o potencjalnej zdolności do wiązania się z DNA z grupy tiadiazinoakrydyn poprzez cyklizację odpowiednich pochodnych 9-imino-4-nitro-9,10-dihydroakrydyny. Zbadano ich zdolność do wiązania się z DNA oraz cytotoksyczność względem kilku linii komórek nowotworwych. Badania aktywności przeciwnowotworowej wobec białaczki P388 wskazały na zgodność tych wyników z wynikami cytotoksyczności in vitro. Wykazano,...
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Optimization of Chemical Functionalities of Indole-2-carboxamides To Improve Allosteric Parameters for the Cannabinoid Receptor 1 (CB1)
Publication5-Chloro-3-ethyl-N-(4-(piperidin-1-yl)phenethyl)-1H-indole-2-carboxamide (1; ORG27569) is a prototypical allosteric modulator for the cannabinoid type 1 receptor (CB1). Here, we reveal key structural requirements of indole-2-carboxamides for allosteric modulation of CB1: a critical chain length at the C3-position, an electron withdrawing group at the C5-position, the length of the linker between the amide bond and the phenyl ring...
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Developments in the synthesis and biological activity of Glycyl-L-Histydyl-L-Lysine derivatives
PublicationWe emphasize on the methods of the synthesis described in the literature and present the aspects of Gly-His-Lys structure modifications that played a key role in scientific research.
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Therapeutic intervention by the simultaneous inhibition of DNA repair and type I or type II DNA topoisomerases: one strategy, many outcomes
PublicationMany anticancer drugs reduce the integrity of DNA, forming strand breaks. This can cause mutations and cancer or cell death if the lesions are not repaired. Interestingly, DNA repair-deficient cancer cells (e.g., those with BRCA1/2 mutations) have been shown to exhibit increased sensitivity to chemotherapy. Based on this observation, a new therapeutic approach termed 'synthetic lethality' has been developed, in which radiation...
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Biomarkers of alcohol consumption in body fluids - possibilities and limitations of application in toxicological analysis
PublicationEthyl alcohol is the most popular legal drug, but its excessive consumption causes social problems. Despite many public campaigns against alcohol use, car accidents, instances of aggressive behaviour, sexual assaults and deterioration in labor productivity caused by inebriated people is still commonplace. Fast and easy diagnosis of alcohol consumption is required in order to introduce proper and effective therapy, and is crucial...
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Effect of modification of 6-[(aminoalkyl)amino]-7H-benzo[e]-perimidin-7-ones on their cytotoxic activity toward sensitive and multidrug resistant tumor cell lines. Synthesis and biological evaluation
PublicationPrzeprowadzono syntezę szeregu nowych pochodnych benzoperimidynowych, a mianowicie: monohydroksybenzoperimidyny i 2-aminobenzoperimidyny. Oznaczono aktywność przeciwnowotworową in vitro powyższych związków względem komórek nowotworowych bez oporności oraz z wykształconą opornością wielolekową. Wyznaczono również powinowactwo pochodnych do błony komórkowej, na kolumnie HPLC z odpowiednim wypełnieniem.
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Synthesisand cytotoxic activity of conjugates of muramyl and normuramyl dipeptides with batracylin derivatives
PublicationOpisano syntezę analogów MDP oraz nor-MDP modyfikowanych w części peptydowej batracyliną i pochodnymi batracyliny. Opracowano udoskonaloną metodę syntezy batracyliny. Zaproponowana metoda pozwala na otrzymanie BAT w skali multi-gramowej. Zsyntetyzowane analogi nie wykazały aktywności cytotoksycznej w badaniach prowadzonych w NCI (Bethesda, USA). W testach in vitro przeprowadzonych w Akademii Medycznej w Gdańsku dwa analogi redukowały...
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Synthesis and antitumor activity of conjugates of muramyldipeptide or normuramyldipeptide with hydroxyacridine/acridone derivatives
PublicationOpisano syntezę analogów MDP oraz nor-MDP modyfikowanych w części peptydowej pochodnymi hydroksyakrydyny/akrydonu i dwóch analogów modyfikowanych pochodnymi 1-nitro-9-hydroksyetylo(propylo)aminoakrydyny. Tylko związki zawierające pochodne 1-nitro-9-hydroksyetylo(propylo)aminoakrydyny wykazały wysoką aktywność cytotoksyczną badaną na 60 liniach ludzkich komórek nowotworowych, na nowotwór prostaty i AIDS-related lymphoma (ARL). Związek...
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Novel dendrimeric lipopeptides with antifungal activity
PublicationZaprojektowano, zsyntezowano i scharakteryzowano serię nowych kationowych lipopeptydów zawierających rozgałęziony, amfifilowy polarny rdzeń strukturalny pochodzący od dendronu (Lys)(Lys)(Lys) oraz łańcuchy C8 i C12 na C-końcu. Otrzymane zwiazki wykazywały aktywność przeciwdrobnoustrojową, w tym szczególnie przeciwgrzybową wobec drożdżaków z rodzaju Candida. Najwyższą aktywność, selektywną wobec drobnoustrojów grzybowych, wykazywały...
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Novel approaches in the synthesis of batracylin and its analogs: rebirth of an old player?
PublicationW pracy opisano batracylinę (BAT), jej syntezę i aktywność biologiczną oraz otrzymane analogi. BAT została wyselekcjonowana przez NCI (Bethesda, USA) w programie poszukiwań nowych potencjalnych leków przeciwnowotworowych. Związek ten w badaniach in vivo na myszach okazał się bardzo aktywny przeciw nowotworowi okrężnicy 38 (Colon 38), trudnemu do wyleczenia przez dotychczas znane leki przeciwnowotworowe. Jest ona skuteczna również...
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Essentials and Perspectives of Computational Modelling Assistance for CNS-oriented Nanoparticle-based Drug Delivery Systems
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Matriptase-2: monitoring and inhibiting its proteolytic activity
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Opioid Growth Factor and its Derivatives as Potential Non-toxic Multifunctional Anticancer and Analgesic Compounds
PublicationIn this paper, we review the structure-activity relationship of OGF and its analogues. We highlight also OGF derivatives with analgesic, immunomodulatory activity and the ability to penetrate the blood-brain barrier and may be used as safe agents enhancing chemotherapy efficacy and improving quality of life in cancer patients. The reviewed papers indicate that Met-enkephalin and its analogues are interesting candidates for the...
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Development of Sulfamoylated 4‑(1-Phenyl‑1H‑1,2,3-triazol-4-yl)phenol Derivatives as Potent Steroid Sulfatase Inhibitors for Efficient Treatment of Breast Cancer
PublicationWe present here the advances achieved in the development of new sulfamoylated 4-(1-phenyl-1H-1,2,3-triazol-4-yl)phenol derivatives as potent steroid sulfatase (STS) inhibitors for the treatment of breast cancer. Prompted by promising biological results and in silico analysis, the initial series of similar compounds were extended, appending a variety of m-substituents at the outer phenyl ring. The inhibition profiles of the newly...
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Cyclic Peptidic Furin Inhibitors Developed by Combinatorial Chemistry
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A Comprehensive Review on the Medicinal Importance; Biological and Therapeutic Efficacy of Lagenaria siceraria (Mol.) (Bottle Gourd) Standley Fruit
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Phosphoroorganic Metal Complexes in Therapeutics
PublicationThe present mini-review highlights recent developments on antitumor activity of metal-based therapeutics which have been a subject of researches for the last few decades. In 1965, Rosenberg found that during an electrolysis on platinum electrodes a complex of Pt is generated which inhibited to a great extent a binary fission in Escherichia coli bacteria. This discovery started a new chapter in medicinal chemistry and the interesting...
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Approaches Towards Better Immunosuppressive Agents
PublicationSeveral classes of compounds are applied in clinics due to their immunosuppressive properties in transplantology and the treatment of autoimmune diseases. Derivatives of mycophe-nolic acid, corticosteroids and chemotherapeutics bearing heterocyclic moieties like methotrexate, azathioprine, mizoribine, and ruxolitinib are active substances with investigated mechanisms of action. However, improved synthetic approaches of known drugs...
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Synthesis and biological activity of mycophenolic acid-amino acid derivatives
PublicationIn search of new immunosuppressants, mycophenolic acid (MPA) was coupled with amino acid methyl esters followed by hydrolysis to analogs bearing free carboxylic groups. The obtained compunds were tested in vitro as growth inhibitors of lymphoid cell line (Jurkat) and human peripheral blood mononuclear cells (PBMC) from healthy donors. According to obtained results recovering of free carboxylic group increased their activity. Additionally,...
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Carbonic anhydrase inhibitors. Synthesis, and molecular structure of novel series N-substituted N'-(2-arylmethylthio-4-chloro-5- methylbenzenesulfonyl)guanidines and their inhibition of human cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XII
PublicationA series of novel N-substituted N'-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)guanidines 9 e41 have been synthesized and investigated as inhibitors of four isoforms of zinc enzyme carbonic anhydrase (CA.EC 4.2.1.1), that is the cytosolic CA I and II, and cancer-associated isozymes CA IX and XII. Against the human CA I investigated compounds showed KI in the range of 87e6506 nM, toward hCA II ranging from 7.8 to 4500 nM,...
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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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Synthesis and biological evaluation of fluorinated N-benzoyl and N-phenylacetoyl derivatives of 3-(4-aminophenyl)-coumarin-7-O-sulfamate as steroid sulfatase inhibitors
PublicationIn the present work, we report convenient methods for the synthesis of 3-(4-aminophenyl)-coumarin-7-O-sulfamate derivatives N-acylated with fluorinated analogues of benzoic or phenylacetic acid as steroid sulfatase (STS) inhibitors. The design of these potential STS inhibitors was supported by molecular modeling techniques. Additionally, computational docking methods were used to determine the binding modes of the synthesized inhibitors...
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Synthesis and biological activity of mycophenolic acid-amino acid derivatives
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Ultrasound assisted rapid synthesis of mefenamic acid based indole derivatives under ligand free Cu-catalysis: Their pharmacological evaluation
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Rosuvastatin based novel 3-substituted isocoumarins / 3-alkylidenephthalides: Ultrasound assisted synthesis and identification of new anticancer agents
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Synthesis and antimicrobial activity of amino acid and peptide derivatives of mycophenolic acid
PublicationThe series of 16 novel amino acid and peptide mycophenolic acid (MPA) derivatives was obtained as potential antibacterial agents. Coupling of MPA with respective amines was optimized with condensing reagents such as EDCI/DMAP and T3P/TEA. Amino acid analogs were received both as methyl esters and also with the free carboxylic group. The biological activity of the products was tested on five references bacterial strains: Klebsiella...
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Novel 2-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)-1-(1,3,5-triazin-2-ylamino)guanidine derivatives: Inhibition of human carbonic anhydrase cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XII, anticancer activity, and molecular modeling studies
PublicationA series of novel 2-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)-1-(6-substituted-4-chloro-1,3,5-triazin-2-ylamino)guanidine derivatives 9–20 have been synthesized by substitution of chlorine atom at the 1,3,5-triazine ring in compounds 5–8 with 3- or 4-aminobenzenesulfonamide and 4-(aminomethyl)benzenesulfonamide hydrochloride. All the synthesized compounds were evaluated for their inhibitory activity toward hCA I, II,...
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Synthesis, anticandidal activity of N3-(4-methoxyfumaroyl)-(S)-2,3-diaminopropanoic amide derivatives – Novel inhibitors of glucosamine-6-phosphate synthase
PublicationNovel FMDP amiders 4-6 have been synthesized and tested against Candida strains. The anticandidal activity has been confined only to Candida albicans. Anticandidal activity of the tested amides has correlated with their inhibitory activity of glucosamine-6-phosphate synthase in cell free extract from Candida albicans.
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Synthesis of functionalized new conjugates of batracylin with tuftsin/ retro-tuftsin derivatives and their biological evaluation
PublicationNew batracylin conjugates with tuftsin/retro-tuftsin derivatives were designed and synthesized using T3P as a coupling agent. The conjugates possess an amide bond formed between the carboxyl group of heterocyclic molecule and the N-termini of the tuftsin/retro-tuftsin chain. The in vitro cytotoxic activity of the new analogues and their precursors was evaluated using a series of human and murine tumor cells. BAT conjugates containing...
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Structural factors affecting affinity of cytotoxic oxathiole-fused chalcones toward tubulin
PublicationSynthesis, in vitro cytotoxic activity, and interaction with tubulin of (E)-1-(6-alkoxybenzo[d][1,3]oxathiol- 5-yl)-3-phenylprop-2-en-1-one derivatives (2) are described. Some of the compounds demonstrated cytotoxic activity at submicromolar concentrations, and the activity could be related to interaction with tubulin at the colchicine binding site. Interaction of selected derivatives with tubulinwas evaluated using molecular modeling,...
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Novel 2-(2-alkylthiobenzenesulfonyl)-3-(phenylprop-2-ynylideneamino)guanidine derivatives as potent anticancer agents – Synthesis, molecular structure, QSAR studies and metabolic stability
PublicationA series of new 2-(2-alkylthiobenzenesulfonyl)-3-(phenylprop-2-ynylideneamino)guanidine derivatives have been synthesized and evaluated in vitro by MTT assays for their antiproliferative activity against cell lines of colon cancer HCT-116, cervical cancer HeLa and breast cancer MCF-7. The obtained results indicated that these compounds display prominent cytotoxic effect. The best anticancer properties have been observed for derivatives...
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New Analogues of Mycophenolic Acid
PublicationMycophenolic acid (MPA) possesses antibacterial, antifungal, antiviral, immunosuppressive and anticancer properties. It is a non-competitive and reversible inhibitor of dehydrogenase inosine-5'-monophosphate (IMPDH). This compound belongs to the immunosuppressive drugs used for the prevention of both acute and chronic transplant rejection. Until now, two derivatives of MPA have been used clinically: mycophenolate mofetil (MMF,...
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Hydrazone Linker as a Useful Tool for Preparing Chimeric Peptide/Nonpeptide Bifunctional Compounds
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Design, synthesis and in vitro biological evaluation of a small cyclic peptide as inhibitor of vascular endothelial growth factor binding to neuropilin-1
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Branched pentapeptides as potent inhibitors of the vascular endothelial growth factor 165 binding to Neuropilin-1: Design, synthesis and biological activity
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Photophysical properties and photocytotoxicity of free and liposome-entrapped diazepinoporphyrazines on LNCaP cells under normoxic and hypoxic conditions
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Photosensitizers Mediated Photodynamic Inactivation Against Virus Particles
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Imidazolidine-4-one derivatives in the search for novel chemosensitizers of Staphylococcus aureus MRSA: Synthesis, biological evaluation and molecular modeling studies
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Amine–alkyl derivatives of hydantoin: New tool to combat resistant bacteria
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Discovery of phenylselenoether-hydantoin hybrids as ABCB1 efflux pump modulating agents with cytotoxic and antiproliferative actions in resistant T-lymphoma
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Design, synthesis and structure–activity relationships of novel phenylalanine-based amino acids as kainate receptors ligands
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Pharmacological characterization and binding modes of novel racemic and optically active phenylalanine-based antagonists of AMPA receptors
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Imidazo-thiazine, -diazinone and -diazepinone derivatives. Synthesis, structure and benzodiazepine receptor binding
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N-Substituted piperazine derivatives as potential multitarget agents acting on histamine H3 receptor and cancer resistance proteins
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Naphtho[1′,2′:4,5]imidazo[1,2-a]pyridine-5,6-diones: Synthesis, enzymatic reduction and cytotoxic activity
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