scholarly journals Synthesis of a New Type of Carbonic Anhydrases Inhibitors

2020 ◽  
Author(s):  
◽  
Aleksandrs Pustenko
Keyword(s):  
Inhibitory Activity ◽  
Antibacterial Agent ◽  
Selective Inhibitor ◽  
Carbonic Anhydrases ◽  
Scientific Publications ◽  
Doctoral Thesis ◽  
Ca Ix ◽  
New Type

The Doctoral Thesis has been prepared as a thematically united collection of scientific publications. It consists of a summary and five scientific publications. Publications have been written in English, their total volume is 39 pages. A new, selective class of CA IX and CA XII inhibitors – 3H-1,2-benzoxathiepine 2,2-dioxides, has been found. A series of 3H-1,2-benzoxathiepine 2,2-dioxide triazolyl, acylamino and aryl derivatives was synthesized. We discovered that furagin, a clinically used antibacterial agent, is a selective inhibitor of CA IX and CA XII. Developing this concept, we synthesized a series of imidazolidine-2,4-dione derivatives. Inhibitory activity on relevant human CA isoforms (I, II, IX, and XII) was determined for all products synthesized within the scope of the Doctoral Thesis.

scholarly journals Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives

2021 ◽  
Vol 22 (11) ◽  
pp. 5482
Author(s):  
Zuo-Peng Zhang ◽  
Ye Zhong ◽  
Zhen-Bin Han ◽  
Lin Zhou ◽  
Hua-Sheng Su ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Human Cancer ◽  
Carbonic Anhydrases ◽  
Inhibitory Effects ◽  
Docking Analysis ◽  
Human Cancer Cell Lines ◽  
Hypoxic Conditions ◽  
Ca Ix ◽  
Topological Polar Surface Area ◽  
Ht 29

A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the “tail approach” and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.

scholarly journals Aryl-4,5-dihydro-1H-pyrazole-1-carboxamide Derivatives Bearing a Sulfonamide Moiety Show Single-digit Nanomolar-to-Subnanomolar Inhibition Constants against the Tumor-associated Human Carbonic Anhydrases IX and XII

2020 ◽  
Vol 21 (7) ◽  
pp. 2621
Author(s):  
Priya Hargunani ◽  
Nikhil Tadge ◽  
Mariangela Ceruso ◽  
Janis Leitans ◽  
Andris Kazaks ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Inhibitory Activity ◽  
Phenyl Ring ◽  
Drug Targets ◽  
Binding Mode ◽  
Docking Studies ◽  
Carbonic Anhydrases ◽  
Single Digit ◽  
Ca Ix ◽  
Shed Light

A series of new 3-phenyl-5-aryl-N-(4-sulfamoylphenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide derivatives was designed here, synthesized, and studied for carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory activity against the human (h) isozymes I, II, and VII (cytosolic, off-target isoforms), and IX and XII (anticancer drug targets). Generally, CA I was not effectively inhibited, whereas effective inhibitors were identified against both CAs II (KIs in the range of 5.2–233 nM) and VII (KIs in the range of 2.3–350 nM). Nonetheless, CAs IX and XII were the most susceptible isoforms to this class of inhibitors. In particular, compounds bearing an unsubstituted phenyl ring at the pyrazoline 3 position showed 1.3–1.5 nM KIs against CA IX. In contrast, a subset of derivatives having a 4-halo-phenyl at the same position of the aromatic scaffold even reached subnanomolar KIs against CA XII (0.62–0.99 nM). Docking studies with CA IX and XII were used to shed light on the derivative binding mode driving the preferential inhibition of the tumor-associated CAs. The identified potent and selective CA IX/XII inhibitors are of interest as leads for the development of new anticancer strategies.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

Polypharmacology of epacadostat: a potent and selective inhibitor of the tumor associated carbonic anhydrases IX and XII

2019 ◽  
Vol 55 (40) ◽  
pp. 5720-5723 ◽  
Author(s):  
Andrea Angeli ◽  
Marta Ferraroni ◽  
Alessio Nocentini ◽  
Silvia Selleri ◽  
Paola Gratteri ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Selective Inhibitor ◽  
Carbonic Anhydrase Inhibitor ◽  
Carbonic Anhydrases ◽  
Indoleamine 2,3 Dioxygenase

Epacadostat (EPA), a selective indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, has been investigatedin vitroas a human (h) Carbonic Anhydrase Inhibitor (CAI).

The Organization of Life before Death in Two Québec Cultural Configurations

1993 ◽  
Vol 27 (1) ◽  
pp. 35-50
Author(s):  
Luce Des Aulniers
Keyword(s):  
Basic Concept ◽  
Data Gathering ◽  
Doctoral Thesis ◽  
Historical Factors ◽  
Personal Experiences ◽  
Life Threatening ◽  
New Type ◽  
The Subject ◽  
Fatal Illness ◽  
Data Gathering And Analysis

This article is based on data from a doctoral thesis about the “anthropology of life-threatening, death and time.” [1] The interpretation is made from twelve life reviews set at homes of people who suffered a serious, but not necessarily fatal illness. Two-cultural configurations are chosen along the axis of rural-urban polarity. It focuses on three types of solidarity, facing the awareness of death: 1) the ethnographic position, in data gathering and analysis. Specific propositions are given concerning the subject and intersubjectivity, cultural generalization of personal experiences, and scientific criteria; 2) what helps cope with illness. Pre-death practices are structured on the basic concept of resistance to illness and preparation for death practices rely on a coherence “test.” The genealogy of practices emerge in six situational and seven historical factors; 3) the conditions of a new type of rite before death and its functions, beside the institutionalization of illness and death.

scholarly journals ‘Messy’ Processing of χ-conotoxin MrIA Generates Homologues with Reduced hNET Potency

Marine Drugs ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 165 ◽  
Author(s):  
Rebekah Ziegman ◽  
Andreas Brust ◽  
Prerna Jha ◽  
Fernanda Cardoso ◽  
Richard Lewis ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Ion Channels ◽  
Inhibitory Activity ◽  
Calcium Influx ◽  
Norepinephrine Transporter ◽  
Selective Inhibitor ◽  
Drug Candidate ◽  
Chronic Neuropathic Pain ◽  
Structure Activity ◽  
Variable Processing

Integrated venomics techniques have shown that variable processing of conotoxins from Conus marmoreus resulted in a dramatic expansion in the number of expressed conotoxins. One conotoxin from C. marmoreus, the χ-conotoxin MrIA, is a selective inhibitor of human norepinephrine transporters (hNET) and therefore a drug candidate for attenuating chronic neuropathic pain. It has been found that “messy” processing of the MrIA transcripts results in the expression of MrIA analogs with different truncations of the pro-peptide that contains portions of the MrIA molecule. The aim of this study was to investigate if variable processing of the expressed peptides results in modulation of the existing hNET pharmacology or creates new pharmacologies. To this end, a number of MrIA analogs found in C. marmoreus venom were synthesized and evaluated for their activity at hNET receptors. While several of the analogs exhibited norepinephrine transporter inhibitory activity comparable to that of MrIA, none significantly improved on the potency of conotoxin MrIA, and those analogs with disrupted pharmacophores produced greatly reduced NET inhibition, confirming previous structure-activity relationships seen on χ-class conopeptides. Additionally, analogs were screened for new activities on ion channels using calcium influx assays, although no major new pharmacology was revealed.

Acyl selenoureido benzensulfonamides show potent inhibitory activity against carbonic anhydrases from the pathogenic bacterium Vibrio cholerae

2017 ◽  
Vol 75 ◽  
pp. 170-172 ◽  
Author(s):  
Andrea Angeli ◽  
Ghulam Abbas ◽  
Sonia Del Prete ◽  
Fabrizio Carta ◽  
Clemente Capasso ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Inhibitory Activity ◽  
Pathogenic Bacterium ◽  
Carbonic Anhydrases ◽  
Potent Inhibitory Activity

Standardization of Antibacterial Bone China

2010 ◽  
Vol 178 ◽  
pp. 367-370
Author(s):  
Li Juan Wang ◽  
Jin Sheng Liang
Keyword(s):  
Antibacterial Agent ◽  
Ceramic Materials ◽  
Antibacterial Mechanism ◽  
Bone China ◽  
New Type

The developments of antibacterial ceramics technology were introduced. A new type of antibacterial agent used in bone china, multifuntional healthy ceramic materials antibacterial mechanism, was discussed. With the quick development of antibacterial bone china technology and market, it was necessary to estabish the antibacterial bone china standard.

Sign in / Sign up

Export Citation Format

Share Document