Phytochemical composition and in -vitro pharmacological evaluation of Emex australis Steinh: A natural source of enzyme inhibitors

Crab apple (Malus baccata (L.) Borkh.) was mainly distributed in Europe as an ornamental plant, but the nutritional properties of its edible fruits were not fully revealed. The aim of the current study was to characterize the phytochemical composition of ripen carb apple fruits and to evaluate their nutritional and antioxidant potentials. The fruits were assayed for moisture and ash content, proteins, lipids, carbohydrates, titratable acidity (TA), pH, total phenolic compounds and natural pigments. Among the analyzed carbohydrates cellulose was found in the highest content (6% dw), followed by sugars (sucrose, glucose and fructose) and 1.8 % dw uronic acids. The total chlorophylls and carotenoids contents in their fruits were 6.51 and 4.80 μg/g fw, respectively. Total monomeric anthocyanins were not detected. The highest content of total phenolic compounds (2.67 mg GAE/g fw) was found in 95 % ethanol extract from fruits, while the total flavonoids were relatively low – 0.1 mg QE/g fw. DPPH assay (17.27 mM TE/g fw) and FRAP assay (14.34 mM TE/g fw) demonstrated in vitro antioxidant activities of crabapple. Malus baccata fruits were evaluated as a rich source of dietary fibers and phenolic compounds with significant antioxidant potential that could be used in human nutrition.

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Synthesis, Molecular Modelling and Antibacterial Activity Against Helicobacter pylori of Novel Diflunisal Derivatives as Urease Enzyme Inhibitors

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180627130208 ◽

2019 ◽

Vol 16 (4) ◽

pp. 392-400 ◽

Cited By ~ 2

Author(s):

Göknil Pelin Coşkun ◽

Teodora Djikic ◽

Sadık Kalaycı ◽

Kemal Yelekçi ◽

Fikrettin Şahin ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibacterial Activity ◽

Enzyme Inhibitors ◽

Binding Modes ◽

Bacterial Strains ◽

Urease Enzyme ◽

H Pylori ◽

Ulcer Treatment ◽

Main Factor

Background:The main factor for the prolongation of the ulcer treatment in the gastrointestinal system would be Helicobacter pylori infection, which can possibly lead to gastrointestinal cancer. Triple therapy is the treatment of choice by today's standards. However, observed resistance among the bacterial strains can make the situation even worse. Therefore, there is a need to discover new targeted antibacterial therapy in order to make success in the eradication of H. pylori infections.Methods:The targeted therapy rule is to identify the related macromolecules that are responsible for the survival of the bacteria. Thus, 2-[(2',4'-difluoro-4-hydroxybiphenyl-3-yl)carbonyl]-N- (substituted)hydrazinocarbothioamide (3-13) and 5-(2',4'-difluoro-4-hydroxybiphenyl-3-yl)-4- (substituted)-2,4-dihydro-3H-1,2,4-triazole-3-thiones (14-17) were synthesized and evaluated for antibacterial activity in vitro against H. pylori.Results:All of the tested compounds showed remarkable antibacterial activity compared to the standard drugs (Ornidazole, Metronidazole, Nitrimidazin and Clarithromycin). Compounds 4 and 13 showed activity as 2µg/ml MIC value.Conclusion:In addition, we have investigated binding modes and energy of the compounds 4 and 13 on urease enzyme active by using the molecular docking tools.

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Chalcones: As potent α-amylase enzyme inhibitors; synthesis, in vitro, and in silico studies

Medicinal Chemistry ◽

10.2174/1573406416666200611103039 ◽

2020 ◽

Vol 16 ◽

Author(s):

Mahboob Ali ◽

Momin Khan ◽

Khair Zaman ◽

Abdul Wadood ◽

Maryam Iqbal ◽

...

Keyword(s):

In Silico ◽

Enzyme Inhibitors ◽

Biological Activities ◽

Condensation Reaction ◽

Type Ii Diabetes Mellitus ◽

Spectroscopic Techniques ◽

Chalcone Derivatives ◽

In Silico Studies ◽

Wide Range

: Background: The inhibition of α-amylase enzyme is one of the best therapeutic approach for the management of type II diabetes mellitus. Chalcone possesses a wide range of biological activities. Objective: In the current study chalcone derivatives (1-17) were synthesized and evaluated their inhibitory potential against α-amylase enzyme. Method: For that purpose, a library of substituted (E)-1-(naphthalene-2-yl)-3-phenylprop-2-en-1-ones was synthesized by ClaisenSchmidt condensation reaction of 2-acetonaphthanone and substituted aryl benzaldehyde in the presence of base and characterized via different spectroscopic techniques such as EI-MS, HREI-MS, 1H-, and 13C-NMR. Results: Sixteen synthetic chalcones were evaluated for in vitro porcine pancreatic α-amylase inhibition. All the chalcones demonstrated good inhibitory activities in the range of IC50 = 1.25 ± 1.05 to 2.40 ± 0.09 μM as compared to the standard commercial drug acarbose (IC50 = 1.34 ± 0.3 μM). Conclusion: Chalcone derivatives (1-17) were synthesized, characterized, and evaluated for their α-amylase inhibition. SAR revealed that electron donating groups in the phenyl ring have more influence on enzyme inhibition. However, to insight the participation of different substituents in the chalcones on the binding interactions with the α-amylase enzyme, in silico (computer simulation) molecular modeling analyses were carried out.

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DDRE-09. DEVELOPING IDO-PROTACS TO IMPROVE IMMUNOTHERAPEUTIC EFFICACY IN PATIENTS WITH GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.254 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii63-ii63

Author(s):

Lakshmi Bollu ◽

Derek Wainwright ◽

Lijie Zhai ◽

Erik Ladomersky ◽

Kristen Lauing ◽

...

Keyword(s):

Protein Degradation ◽

Time Course ◽

Immune Cell ◽

Enzyme Inhibitors ◽

Tumor Development ◽

Ubiquitin Proteasome System ◽

Degradation Pathway ◽

Specific Protein ◽

Cell Functions

Abstract INTRODUCTION Indoleamine 2,3-dioxygenase 1 (IDO; IDO1) is a rate-limiting enzyme that metabolizes the essential amino acid tryptophan into kynurenine. Recent work by our group has revealed that IDO promotes tumor development and suppresses immune cell functions independent of its enzyme activity. Moreover, pharmacologic IDO enzyme inhibitors that currently serve as the only class of drugs available for targeting immunosuppressive IDO activity, fail to improve the survival of patients with GBM. Here, we developed IDO-Proteolysis Targeting Chimeras (IDO-PROTACs). PROTACs bind to a specific protein and recruit an E3 ubiquitin ligase that enhance proteasome-mediated degradation of the target protein. METHODS A library of ≥100 IDO-PROTACs were developed by joining BMS986205 (IDO binder) with a linker group to various E3-ligase ligands. Western blot analysis of PROTAC-induced IDO degradation was tested in vitro among multiple human and mouse GBM cell lines including U87, GBM6, GBM43 and GL261 along a time course ranging between 1–96 hours of treatment and at varying concentrations. The mechanism of IDO protein degradation was investigated using pharmacologic ligands that inhibit or compete with the proteasome-mediated protein degradation pathway. RESULTS Primary screening identified several IDO-PROTACs with IDO protein degradation potential. Secondary screening showed that our lead compound has a DC50 value of ~0.5µM with an ability to degrade IDO in all GBM cells analyzed, and an initial activity within 12 hours of treatment that extended for up to 96 hours. Mutating the CRBN-binding ligand, pretreatment with the ubiquitin proteasome system inhibitors MG132 or MLN4924 or using unmodified parental compound all inhibited IDO protein degradation. CONCLUSIONS This study developed an initial IDO-PROTAC technology that upon further optimization, can neutralize both IDO enzyme and non-enzyme immunosuppressive effects. When combined with other forms of immunotherapy, IDO-PROTACs have the potential to substantially enhance immunotherapeutic efficacy in patients with GBM.

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Phytochemical Composition and Biological Activities of Scorzonera Species

International Journal of Molecular Sciences ◽

10.3390/ijms22105128 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5128

Author(s):

Karolina Lendzion ◽

Agnieszka Gornowicz ◽

Krzysztof Bielawski ◽

Anna Bielawska

Keyword(s):

Biological Activities ◽

Folk Medicine ◽

Quinic Acid ◽

Hepatoprotective Activity ◽

Phytochemical Composition ◽

Starting Point ◽

Microbial Infections ◽

Bacteria And Fungi ◽

Bioactive Potential

The genus Scorzonera comprises nearly 200 species, naturally occurring in Europe, Asia, and northern parts of Africa. Plants belonging to the Scorzonera genus have been a significant part of folk medicine in Asia, especially China, Mongolia, and Turkey for centuries. Therefore, they have become the subject of research regarding their phytochemical composition and biological activity. The aim of this review is to present and assess the phytochemical composition, and bioactive potential of species within the genus Scorzonera. Studies have shown the presence of many bioactive compounds like triterpenoids, sesquiterpenoids, flavonoids, or caffeic acid and quinic acid derivatives in extracts obtained from aerial and subaerial parts of the plants. The antioxidant and cytotoxic properties have been evaluated, together with the mechanism of anti-inflammatory, analgesic, and hepatoprotective activity. Scorzonera species have also been investigated for their activity against several bacteria and fungi strains. Despite mild cytotoxicity against cancer cell lines in vitro, the bioactive properties in wound healing therapy and the treatment of microbial infections might, in perspective, be the starting point for the research on Scorzonera species as active agents in medical products designed for miscellaneous skin conditions.

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