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Molecules (Basel, Switzerland) May 2023Cancer is threatening the survival of human beings all over the world. Phototherapy (including photothermal therapy (PTT) and photodynamic therapy (PDT)) and bioimaging... (Review)
Review
Cancer is threatening the survival of human beings all over the world. Phototherapy (including photothermal therapy (PTT) and photodynamic therapy (PDT)) and bioimaging are important tools for imaging-mediated cancer theranostics. Diketopyrrolopyrrole (DPP) dyes have received more attention due to their high thermal and photochemical stability, efficient reactive oxygen species (ROS) generation and thermal effects, easy functionalization, and tunable photophysical properties. In this review, we outline the latest achievements of DPP derivatives in cancer therapy and imaging over the past three years. DPP-based conjugated polymers and small molecules for detection, bioimaging, PTT, photoacoustic imaging (PAI)-guided PTT, and PDT/PTT combination therapy are summarized. Their design principles and chemical structures are highlighted. The outlook, challenges, and future opportunities for the development of DPP derivatives are also presented, which will give a future perspective for cancer treatment.
Topics: Humans; Phototherapy; Pyrroles; Ketones; Neoplasms; Nanoparticles; Photochemotherapy
PubMed: 37241837
DOI: 10.3390/molecules28104097 -
Molecules (Basel, Switzerland) Dec 2022Herein, we describe the synthesis and characterization of fused pyrroles in cholestane and norcholestane side chains derived from kryptogenin and diosgenin,...
Herein, we describe the synthesis and characterization of fused pyrroles in cholestane and norcholestane side chains derived from kryptogenin and diosgenin, respectively. Both conventional and microwave heating techniques were used to synthesize the steroidal pyrroles from primary amines, with the microwave method producing the highest yields. In particular, the norcholestane pyrroles were tested as acaricides against the two-spotted spider mite ( Koch) under laboratory conditions and as plant growth promoters on habanero pepper ( Jacq) under greenhouse conditions.
Topics: Animals; Acaricides; Pyrroles; Tetranychidae; Capsicum; Cholestanes
PubMed: 36500556
DOI: 10.3390/molecules27238466 -
Molecules (Basel, Switzerland) Dec 2020The subject of the work was the synthesis of new derivatives of1-pyrrolo[3,4-c]pyridine-1,3(2)-dione with potential analgesic and sedative activity. Eight compounds...
The subject of the work was the synthesis of new derivatives of1-pyrrolo[3,4-c]pyridine-1,3(2)-dione with potential analgesic and sedative activity. Eight compounds werereceived. The analgesic activity of the new compounds was confirmed in the "hot plate" test and in the "writhing" test. All tested imides - were more active in the "writhing" test than aspirin, and two of them, and , were similar to morphine. In addition, all of the new imides inhibited the locomotor activity in mice to a statistically significant extent, and two of them also prolonged the duration of thiopental sleep.On the basis of the results obtained for the previously synthesized imides and the results presented in this paper, an attempt was madeto determine the relationship between thechemical structure of imides and their analgesic and sedativeproperties.
Topics: Analgesics; Animals; Hypnotics and Sedatives; Locomotion; Male; Mice; Pyridines; Pyrroles; Structure-Activity Relationship
PubMed: 33322767
DOI: 10.3390/molecules25245883 -
Biomacromolecules Jul 2022Biomaterials capable of precisely controlling the delivery of agrochemicals/biologics/drugs/fragrances have significant markets in the agriscience/healthcare industries....
Biomaterials capable of precisely controlling the delivery of agrochemicals/biologics/drugs/fragrances have significant markets in the agriscience/healthcare industries. Here, we report the development of degradable electroactive polymers and their application for the controlled delivery of a clinically relevant drug (the anti-inflammatory dexamethasone phosphate, DMP). Electroactive copolymers composed of blocks of polycaprolactone (PCL) and naturally occurring electroactive pyrrole oligomers (e.g., bilirubin, biliverdin, and hemin) were prepared and solution-processed to produce films (optionally doped with DMP). A combination of in silico/in vitro/in vivo studies demonstrated the cytocompatibility of the polymers. The release of DMP in response to the application of an electrical stimulus was observed to be enhanced by ca. 10-30% relative to the passive release from nonstimulated samples in vitro. Such stimuli-responsive biomaterials have the potential for integration devices capable of delivering a variety of molecules for technical/medical applications.
Topics: Biocompatible Materials; Electricity; Polymers; Pyrroles
PubMed: 35748772
DOI: 10.1021/acs.biomac.2c00516 -
Journal of Pharmacy & Pharmaceutical... 2022With the significant increase of patients suffering from different types of cancer, it is evident that prompt measures in the development of novel and effective agents... (Review)
Review
With the significant increase of patients suffering from different types of cancer, it is evident that prompt measures in the development of novel and effective agents need to be taken. Pyrrole moiety has been found in various active compounds with anti-inflammatory, antiseptic, antibacterial, lipid-lowering and anticancer properties. Recent advances in the exploration of highly active and selective cytotoxic structures containing pyrrole motifs have shown promising data for future investigations. Accordingly, this review presents an overview of recent developments in the pyrrole derivatives as anticancer agents, with a main focus towards the key moieties required for the anti-tumor activities. Pyrrole molecules comprising prominent targeting capacities against microtubule polymerization, tyrosine kinases, cytochrome p450 family 1, histone deacetylase and bcl-2 proteins were reported. In addition, several mechanisms of action, such as apoptosis, cell cycle arrest, inhibiting kinases, angiogenesis, disruption of cell migration, modulation of nuclear receptor responsiveness and others were analyzed. Furthermore, in most of the discussed cases we provided synthesis schemes of the mentioned molecules. Overall, the utilization of pyrrole scaffold for the design and synthesis of novel anticancer drugs could be a promising approach for future investigations.
Topics: Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cytochrome P-450 Enzyme System; Genes, bcl-2; Histone Deacetylases; Humans; Microtubules; Protein-Tyrosine Kinases; Pyrroles; Structure-Activity Relationship
PubMed: 34995473
DOI: 10.18433/jpps32417 -
Molecules (Basel, Switzerland) Sep 2022Benzimidazole is an important heterocyclic fragment, present in many biologically active compounds with a great variety of therapeutic purposes. Most of the... (Review)
Review
Benzimidazole is an important heterocyclic fragment, present in many biologically active compounds with a great variety of therapeutic purposes. Most of the benzimidazole activities are explained through the existence of 1,3-tautomeric equilibrium. As the binding affinity of each tautomer to a protein target depends on an established bioactive conformation, the effect of tautomers on the ligand protein binding mechanism is determinant. In this work, we searched and analyzed a series of reported C-NMR spectra of benzazoles and benzazolidine-2-thiones with the purpose of estimating their tautomeric equilibrium. Herein, several approaches to determine this problem are presented, which makes it a good initial introduction to the non-expert reader. This chemical shift difference and C4/C7 signals of benzimidazolidine-2-thione and 1-methyl-2-thiomethylbenzimidazole as references were used in this work to quantitatively calculate, in solution, the pyrrole-pyridine tautomeric ratio in equilibrium. The analysis will help researchers to correctly assign the chemical shifts of benzimidazoles and to calculate their intracyclic or exocyclic tautomeric ratio as well as mesomeric proportion in benzimidazoles.
Topics: Benzimidazoles; Ligands; Pyridines; Pyrroles; Thiones
PubMed: 36234805
DOI: 10.3390/molecules27196268 -
Molecules (Basel, Switzerland) Feb 2020Nitroxides are broadly used as molecular probes and labels in biophysics, structural biology, and biomedical research. Resistance of a nitroxide group bearing an...
Nitroxides are broadly used as molecular probes and labels in biophysics, structural biology, and biomedical research. Resistance of a nitroxide group bearing an unpaired electron to chemical reduction with low-molecular-weight antioxidants and enzymatic systems is of critical importance for these applications. The redox properties of nitroxides are known to depend on the ring size (for cyclic nitroxides) and electronic and steric effects of the substituents. Here, two highly strained nitroxides, 5-(-butyl)-5-butyl-2,2-diethyl-3-hydroxypyrrolidin-1-oxyl () and 2-(-butyl)-2-butyl-5,5-diethyl-3,4-bis(hydroxymethyl)pyrrolidin-1-oxyl (), were prepared via a reaction of the corresponding 2--butyl-1-pyrroline 1-oxides with butyllithium. Thermal stability and kinetics of reduction of the new nitroxides by ascorbic acid were studied. Nitroxide showed the highest resistance to reduction.
Topics: Antioxidants; Biomedical Research; Electron Transport; Nitrogen Oxides; Organometallic Compounds; Oxidation-Reduction; Oxides; Pyrroles
PubMed: 32075085
DOI: 10.3390/molecules25040845 -
Journal of the American Chemical Society Aug 2021Herein, we report a reaction that selectively generates 3-arylpyridine and quinoline motifs by inserting aryl carbynyl cation equivalents into pyrrole and indole cores,...
Herein, we report a reaction that selectively generates 3-arylpyridine and quinoline motifs by inserting aryl carbynyl cation equivalents into pyrrole and indole cores, respectively. By employing α-chlorodiazirines as thermal precursors to the corresponding chlorocarbenes, the traditional haloform-based protocol central to the parent Ciamician-Dennstedt rearrangement can be modified to directly afford 3-(hetero)arylpyridines and quinolines. Chlorodiazirines are conveniently prepared in a single step by oxidation of commercially available amidinium salts. Selectivity as a function of pyrrole substitution pattern was examined, and a predictive model based on steric effects is put forward, with DFT calculations supporting a selectivity-determining cyclopropanation step. Computations surprisingly indicate that the stereochemistry of cyclopropanation is of little consequence to the subsequent electrocyclic ring opening that forges the pyridine core, due to a compensatory homoaromatic stabilization that counterbalances orbital-controlled torquoselectivity effects. The utility of this skeletal transform is further demonstrated through the preparation of quinolinophanes and the skeletal editing of pharmaceutically relevant pyrroles.
Topics: Azirines; Carbon; Density Functional Theory; Indoles; Molecular Structure; Pyrroles
PubMed: 34286965
DOI: 10.1021/jacs.1c06287 -
Molecules (Basel, Switzerland) Jun 2017This review covers the synthesis of coumarin-porphyrin, coumarin-phthalocyanine and coumarin-corrole conjugates and their potential applications. While... (Review)
Review
This review covers the synthesis of coumarin-porphyrin, coumarin-phthalocyanine and coumarin-corrole conjugates and their potential applications. While coumarin-phthalocyanine conjugates were obtained almost exclusively by tetramerization of coumarin-functionalized phthalonitriles, coumarin-porphyrin and coumarin-corrole conjugates were prepared by complementary approaches: (a) direct synthesis of the tetrapyrrolic macrocycle using formylcoumarins and pyrrole or (b) by functionalization of the tetrapyrrolic macrocycle. In the last approach a range of reaction types were used, namely 1,3-dipolar cycloadditions, hetero-Diels-Alder, Sonogashira, alkylation or acylation reactions. This is clearly a more versatile approach, leading to a larger diversity of conjugates and allowing the access to conjugates bearing one to up to 16 coumarin units.
Topics: Alkylation; Coumarins; Indoles; Isoindoles; Molecular Structure; Porphyrins; Pyrroles
PubMed: 28617340
DOI: 10.3390/molecules22060994 -
Drug Design, Development and Therapy 2019Recent advances in the understanding of the pathophysiology of ulcerative colitis (UC) have led to the expansion of our therapeutic arsenal. Conventional treatment... (Review)
Review
Recent advances in the understanding of the pathophysiology of ulcerative colitis (UC) have led to the expansion of our therapeutic arsenal. Conventional treatment options, including aminosalicylates, corticosteroids, thiopurines, and calcineurin inhibitors, fail to control the disease in a significant proportion of patients. Approximately 25-50% of the patients treated with tumor necrosis factor antibodies (anti-TNFα) are primary and secondary non-responders to therapy. Tofacitinib is a novel orally administered small synthetic molecule that inhibits a homologous family of enzymes, termed Janus kinases that modulate multiple key cytokines involved in the pathogenesis of UC. Phase II and III trials showed promising results in UC, leading the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to approve its administration for the induction and maintenance of remission in moderate-to-severe UC. Herein, we review tofacitinib for the management of UC, its mechanism of action pharmacokinetic properties, efficacy, and safety.
Topics: Administration, Oral; Colitis, Ulcerative; Humans; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles
PubMed: 31819376
DOI: 10.2147/DDDT.S182891