Recent Updates on Pyrazolines Derivatives as Promising Candidates for Neuropsychiartic and Neurodegenerative disorders

2021 ◽  
Vol 21 ◽  
Author(s):  
T. M. Rangarajan ◽  
Bijo Mathew
Keyword(s):  
Neurodegenerative Disorders ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Phenyl Group ◽  
Inhibitory Effect ◽  
Remarkable Effect ◽  
Mao B ◽  
Wide Range ◽  
Mao A ◽  
Central Nervous Systems

: Pyrazolines are five membered heterocyclic compounds containing two nitrogen atoms represent a privilege scaffold for various bioactive compounds with diverse pharmacological activities. Chalcones and hydrazine derivatives are excellent precursors for pyrazoline, which provide sites for manipulation at N1, 3- and 5-positions of pyrazoline which results a wide range of pyrazoline structures. This method creates a new asymmetric centre at 5-position and extent of conjugation from phenyl group to N1-nitrogen (Fig. 2) that could greatly enhances the physiochemical and pharmacological properties towards target enzymes and hence they are reported to be having wide spectrum of biological activities such as anti-cancer, anti-inflammatory, etc. Most importantly, they have remarkable effect on central nervous systems (CNS). Several reports show that the pyrazoline derivatives have significant inhibitory effect towards the monoamine oxidase enzymes (MAOs) which are known to be responsible for neurodegenerative disorders. These enzymes have two isoforms namely MAO-A and MAO-B which are, in particular, responsible for psychiatric and neurological disorders respectively. Chalcones, generally, are potential and more selective towards MAO-B inhibitions whereas pyrazolines derived from chalcones turned into selective towards MAO-A inhibitions due to maybe the presence of two nitrogen heteroatoms. Therefore, these two derivatives are received much attention among the medicinal chemists as they could solve entire CNS related issues; however pyrazolines are not studied as much as chalcones. Our group has already documented the importance of pyrazolines towards MAO-A inhibition in 2013. With their growing importance many studies on pyrazolines are being carried out constantly for MAO-A inhibition. Therefore, in the present work, we report an update on pyrazolines as potential MAOs inhibitors that are reported during 2014 to date.

Effect of guaianolides in the meiosis reinitiation of amphibian oocytes

Zygote ◽  
2016 ◽  
Vol 25 (1) ◽  
pp. 10-16 ◽  
Author(s):  
J. Zapata-Martínez ◽  
G. Sánchez-Toranzo ◽  
F. Chaín ◽  
C.A.N. Catalán ◽  
M.I. Bühler
Keyword(s):  
Biological Activities ◽  
Wide Spectrum ◽  
Sesquiterpene Lactones ◽  
Inhibitory Effect ◽  
Biological Molecules ◽  
Plant Metabolites ◽  
Major Mechanism ◽  
Bufo Arenarum ◽  
Asteraceae Family

SummarySesquiterpene lactones (STLs) are a large and structurally diverse group of plant metabolites generally found in the Asteraceae family. STLs exhibit a wide spectrum of biological activities and it is generally accepted that their major mechanism of action is the alkylation of the thiol groups of biological molecules. The guaianolides is one of various groups of STLs. Anti-tumour and anti-migraine effects, an allergenic agent, an inhibitor of smooth muscle cells and of meristematic cell proliferation are only a few of the most commonly reported activities of STLs. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under stimulus with progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. There are previous records of the inhibitory effect of dehydroleucodin (DhL), a guaianolide lactone, on the progression of meiosis. It has been also shown that DhL and its 11,13-dihydroderivative (2H-DhL; a mixture of epimers at C-11) act as blockers of the resumption of meiosis in fully grown ovarian oocytes from the amphibian Rhinella arenarum (formerly classified as Bufo arenarum). The aim of this study was to analyze the effect of four closely related guaianolides, i.e., DhL, achillin, desacetoxymatricarin and estafietin as possible inhibitors of meiosis in oocytes of amphibians in vitro and discuss some structure–activity relationships. It was found that the inhibitory effect on meiosis resumption is greater when the lactone has two potentially reactive centres, either a α,β–α′,β′-diunsaturated cyclopentanone moiety or an epoxide group plus an exo-methylene-γ-lactone function.

scholarly journals Evaluation of Binding of Rosmarinic Acid with Human Transferrin and Its Impact on the Protein Structure: Targeting Polyphenolic Acid-Induced Protection of Neurodegenerative Disorders

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Anas Shamsi ◽  
Saleha Anwar ◽  
Mohd Shahbaaz ◽  
Taj Mohammad ◽  
Mohamed F. Alajmi ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Rosmarinic Acid ◽  
Natural Compound ◽  
Iron Homeostasis ◽  
Biological Activities ◽  
Pivotal Role ◽  
Titration Calorimetry ◽  
Static Mode ◽  
Human Transferrin ◽  
Wide Range

Rosmarinic acid (RA) is a natural compound that is gaining wide popularity owing to its broad-spectrum biological activities. RA is known for its wide range of medicinal properties and therapeutic applications in a vast range of neurodegenerative disorders thus making it a vital natural compound. Human transferrin (hTf) is a clinically significant protein that plays a pivotal role in maintaining iron homeostasis. The importance of studies pertaining to hTf is attributable to the pivotal role of iron deposition in CNS in neurodegenerative disorders. The study was intended to have an insight into the interaction between RA and hTf employing multispectroscopic approach, molecular docking, and molecular dynamic simulation studies. Fluorescence quenching studies revealed that RA shows an excellent binding affinity to hTf with a binding constant ( K ) of 107 M-1 and is guided by static mode of quenching. Isothermal titration calorimetry (ITC) further validated the spontaneous nature of binding. The estimation of enthalpy change (∆H) and entropy change (∆S) suggested that the RA-hTf complex formation is driven by hydrogen bonding, thereby making this process seemingly specific. Further, Fourier transform infrared (FTIR) and circular dichroism (CD) spectra suggested that RA induces conformational and structural changes in hTf. Additionally, molecular dynamics (MD) studies were carried out to investigate the stability of the hTf and hTf–RA system and suggested that binding of RA induces structural alteration in hTf with free hTf being more stable. This study provides a rationale to use RA in drug development against neurodegenerative disorders by designing novel functional foods containing RA.

scholarly journals β-Asarone Increases Chemosensitivity by Inhibiting Tumor Glycolysis in Gastric Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Heyun Tao ◽  
Xuelian Ding ◽  
Jian Wu ◽  
Shenlin Liu ◽  
Wei Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Biological Activities ◽  
Hypoxia Inducible Factor ◽  
Chinese Herb ◽  
Lactic Dehydrogenase ◽  
Inhibitory Effect ◽  
Pyruvate Dehydrogenase Kinase ◽  
Dependent Manner ◽  
Tumor Glycolysis ◽  
Wide Range

β-asarone is the main active ingredient of the Chinese herb Rhizoma Acori Tatarinowii, which exhibits a wide range of biological activities. It was confirmed to be an efficient cytotoxic agent against gastroenteric cancer cells. However, the exact mechanism of β-asarone in gastric cancer (GC) remains to be elucidated. The present study showed the inhibitory effect of β-asarone on three types of different differentiation stage GC cell lines (MGC803, SGC7901, and MKN74) in a dose-dependent manner. Meanwhile, the synergistic sensitivity of β-asarone and cisplatin was confirmed by using the median-effect principle. Flow cytometry assay revealed that under both normoxia and CoCl2-induced hypoxia conditions, β-asarone can induce apoptosis of GC cells, which can block GC cells in the cell cycle G2/M phase, showing obvious subdiploid peak. Moreover, the activity of lactic dehydrogenase (LDH), an enzyme that plays an important role in the final step of tumor glycolysis, was significantly decreased in GC cells following treatment with β-asarone. Mechanistically, β-asarone can reduce pyruvate dehydrogenase kinase (PDK) 1, phospho(p)-PDK1, PDK4, hypoxia-inducible factor 1-α (HIF1α), c-myc, STAT5, and p-STAT5 expression, which revealed how β-asarone affects tumor glycolysis. In conclusion, the present study provided evidence in support of the hypothesis that the increase of chemotherapy sensitization by β-asarone is associated with the inhibition of tumor glycolysis.

scholarly journals 5-(4H)-Oxazolones and Their Benzamides as Potential Bioactive Small Molecules

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3173
Author(s):  
Evangelos Mavridis ◽  
Eleftherios Bermperoglou ◽  
Eleni Pontiki ◽  
Dimitra Hadjipavlou-Litina
Keyword(s):  
Lipid Peroxidation ◽  
Biological Activities ◽  
Phenyl Group ◽  
Docking Studies ◽  
Nucleophilic Attack ◽  
The Novel ◽  
Lipoxygenase Inhibitor ◽  
Wide Range ◽  
Inhibit Lipid Peroxidation

The five membered heterocyclic oxazole group plays an important role in drug discovery. Oxazolones present a wide range of biological activities. In this article the synthesis of 4-substituted-2-phenyloxazol-5(4H)-ones from the appropriate substituted aldehydes via an Erlenmeyer–Plochl reaction is reported. Subsequently, the corresponding benzamides were produced via a nucleophilic attack of a secondary amine on the oxazolone ring applying microwave irradiation. The compounds are obtained in good yields up to 94% and their structures were confirmed using IR, 1H-NMR, 13C-NMR and LC/MS data. The in vitro anti-lipid peroxidation activity and inhibitory activity against lipoxygenase and trypsin induced proteolysis of the novel derivatives were studied. Inhibition of carrageenin-induced paw edema (CPE) and nociception was also determined for compounds 4a and 4c. Oxazolones 2a and 2c strongly inhibit lipid peroxidation, followed by oxazolones 2b and 2d with an average inhibition of 86.5%. The most potent lipoxygenase inhibitor was the bisbenzamide derivative 4c, with IC50 41 μM. The benzamides 3c, 4a–4e and 5c were strong inhibitors of proteolysis. The replacement of the thienyl moiety by a phenyl group does not favor the protection. Compound 4c inhibited nociception higher than 4a. The replacement of thienyl groups by phenyl ring led to reduced biological activity. Docking studies of the most potent LOX inhibitor highlight interactions through allosteric mechanism. All the potent derivatives present good oral bioavailability.

scholarly journals Annurca Apple Polyphenol Extract Affects Acetyl- Cholinesterase and Mono-Amine Oxidase In Vitro Enzyme Activity

2021 ◽  
Vol 14 (1) ◽  
pp. 62
Author(s):  
Rosarita Nasso ◽  
Valentina Pagliara ◽  
Stefania D’Angelo ◽  
Rosario Rullo ◽  
Mariorosario Masullo ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Neurodegenerative Disorders ◽  
Amine Oxidase ◽  
Biological Properties ◽  
Human Neuroblastoma ◽  
Mao B ◽  
Brain Functions ◽  
Mao A ◽  
Ic50 Values

In this study, we explored the ability of Annurca apple flesh polyphenol extract (AFPE) to affect the activity of key enzymes involved in neurodegenerative disorders—in particular, Acetyl- and Butirryl-cholinesterases, and type A and B monoamine oxidase. The effect of AFPE on enzyme activity was analyzed by in vitro enzyme assays, and the results showed concentration-dependent enzyme inhibition, with IC50 values corresponding to 859 ± 18 µM and 966 ± 72 µM for AChE and BuChE respectively, and IC50 corresponding to 145 ± 3 µM and 199 ± 7 µM for MAO-A and MAO-B, respectively, with a preference for MAO-A. Moreover, in this concentration range, AFPE did not affect the viability of human neuroblastoma SH-SY5Y and fibroblast BJ-5ta cell lines, as determined by an MTT assay. In conclusion, our results demonstrate that AFPE shows the new biological properties of inhibiting the activity of enzymes that are involved in brain functions, neurodegenerative disorders, and aging.

Ursolic Acid in Cancer Treatment and Metastatic Chemoprevention: From Synthesized Derivatives to Nanoformulations in Preclinical Studies

2019 ◽  
Vol 19 (4) ◽  
pp. 245-256 ◽  
Author(s):  
Junjie Zou ◽  
Juanfang Lin ◽  
Chao Li ◽  
Ruirui Zhao ◽  
Lulu Fan ◽  
...  
Keyword(s):  
Ursolic Acid ◽  
Cancer Metastasis ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Cancer Drug ◽  
Therapeutic Effects ◽  
Candidate Drug ◽  
Wide Range ◽  
Anti Cancer ◽  
Tumor Growth And Metastasis

Background:Cancer metastasis has emerged as a major public health threat that causes majority of cancer fatalities. Traditional chemotherapeutics have been effective in the past but suffer from low therapeutic efficiency and harmful side-effects. Recently, it has been reported ursolic acid (UA), one of the naturally abundant pentacyclic triterpenes, possesses a wide range of biological activities including anti-inflammatory, anti-atherosclerotic, and anti-cancer properties. More importantly, UA has the features of low toxicity, liver protection and the potential of anti-cancer metastasis.Objective:This article aimed at reviewing the great potential of UA used as a candidate drug in the field of cancer therapy relating to suppression of tumor initiation, progression and metastasis.Methods:Selective searches were conducted in Pubmed, Google Scholar and Web of Science using the keywords and subheadings from database inception to December 2017. Systemic reviews are summarized here.Results:UA has exhibited chemopreventive and therapeutic effects of cancer mainly through inducing apoptosis, inhibiting cell proliferation, preventing tumor angiogenesis and metastatic. UA nanoformulations could enhance the solubility and bioavailability of UA as well as exhibit better inhibitory effect on tumor growth and metastasis.Conclusion:The information presented in this article can provide useful references for further studies on making UA a promising anti-cancer drug, especially as a prophylactic metastatic agent for clinical applications.

Synthesis of Oridonin Derivatives via Mizoroki-Heck Reaction and Click Chemistry for Cytotoxic Activity

2019 ◽  
Vol 19 (7) ◽  
pp. 935-947
Author(s):  
Wei Hou ◽  
Qiuju Fan ◽  
Lin Su ◽  
Hongtao Xu
Keyword(s):  
Natural Products ◽  
Cancer Cells ◽  
Heck Reaction ◽  
Biological Activities ◽  
Phenyl Group ◽  
Structure Modification ◽  
Parent Molecule ◽  
Wide Range ◽  
Negative Effect ◽  
Derivatives Of

Background:Natural products (NPs) are evolutionarily chosen “privileged structures” that have a profound impact upon the anticancer drug discovery and development progress. However, the search for new drugs based on structure modification of NPs has often been hindered due to the tedious and complicated synthetic pathways. Fortunately, Mizoroki-Heck reaction and copper-catalyzed alkyne-azide cycloaddition (CuAAC) could provide perfect strategies for selective modification on NPs even in the presence of liable functionalities.Objective:Here, we used oridonin, an ent-kaurane diterpenoid that showed a wide range of biological activities, as a parent molecule for the generation of analogues with anticancer activity.Methods:Derivatives of oridonin were generated based on the structure-activity relationship study of oridonin and synthesized via Mizoroki-Heck reaction and CuAAC. The cytotoxicity of new oridonin derivatives were evaluated on both cancer cells and normal cells. Furthermore, the apoptotic effect and cell cycle arrest effect of the selected potent analogue were evaluated by flow cytometry and western blotting analysis.Results:Two series of novel C-14 and C-17 modified derivatives of oridonin were obtained via Heck reaction and copper-catalyzed alkyne-azide cycloaddition (CuAAC), respectively. In vitro antiproliferative activities showed that the introduction of C-14 (2-triazole)acetoxyl- moiety could retain or enhance cytotoxicity, whereas the introduction of C-17 phenyl ring might exert negative effect. Further studies demonstrated that derivative 23 exhibited broad-spectrum antiproliferative activity, effectively overcame drug-resistance and showed weak cytotoxicity on non-cancer cells. Preliminary mechanistic studies indicated that 23 might cause G2/M phase arrest and induce apoptosis in PC-3 cells.Conclusion:Mizoroki-Heck reaction and CuAAC are perfect strategies for structure modification of complex natural products. The introduction of C-14 (2-triazole)acetoxyl- moiety could retain or enhance the cytotoxicity of oridonin, the introduction of C-17 phenyl group might exert negative effect on its cytotoxicity.

Sulfonamides and Sulphonyl Ester of Quinolines as Non-Acidic, Non- Steroidal, Anti-inflammatory Agents

2020 ◽  
Vol 17 ◽  
Author(s):  
Bilquees Bano ◽  
Kanwal ◽  
Khalid Mohammed Khan ◽  
Almas Jabeen ◽  
Aisha Faheem ◽  
...  
Keyword(s):  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Inflammatory Activity ◽  
Spectroscopic Techniques ◽  
Wide Range ◽  
Anti Inflammatory ◽  
Hydroxy Quinoline ◽  
Synthetic Derivatives ◽  
Derivatives Of

Background:: Quinolines are important class of heterocyclic compounds possessing wide range of biological activities. Previously, we had identified Schiff bases of quinoline as potential anti-inflammatory agents, thus the current work is the continuation of our previous study. Objective:: In the current study 3-, 5-, and 8-sulfonamide and 8-sulfonate derivatives of quinoline (1-50) were synthesized and their antiinflammatory potential was evaluated. These synthetic analogs were evaluated for their anti-inflammatory activity via ROS (Reactive oxygen species) inhibitory effect produced from phagocytes from human whole blood. Methods:: The sulfonamide and sulfonate derivatives of quinoline were synthesized via treating 5-, 3-, 8-amino, and 8-hydroxy quinoline with different substituted sulfonyl chlorides in pyridine. The synthetic molecules were characterized using various spectroscopic techniques and screened for their anti-inflammatory potential. Results and Discussion:: Among the synthetic derivatives 1-50, six compounds showed good to moderate anti-inflammatory activity. Compounds 47 (IC50 = 2.9 ± 0.5 μg/mL), 36 (IC50 = 3.2 ± 0.2 μg/mL), and 24 (IC50 = 6.7 ± 0.3 μg/mL) exhibited enhanced activity as compared to the standard ibuprofen (IC50 = 11.2 ± 1.9 μg/mL). Compounds 20 (IC50 = 25.5 ± 0.7 μg/mL), 50 (IC50 = 42.9 ± 5.6 μg/mL), and 8 (IC50 = 53.9 ± 3.1 μg/mL) were moderately active, however, rest of the compounds were found to be inactive. Conclusion:: The sulfonamide and sulfonate derivatives of quinoline were found to have promising anti-inflammatory activity. Further studies on the modification of these molecules may leads to the discovery of new and potential anti-inflammatory agents.

scholarly journals RHODOMYRTUS TOMENTOSA: A PHYTOCHEMICAL AND PHARMACOLOGICAL REVIEW

2016 ◽  
Vol 10 (1) ◽  
pp. 10 ◽  
Author(s):  
Hazrulrizawati Abd Hamid ◽  
Senait Sileshi Zeyohannes Roziasyahira M ◽  
Mashitah M Yusoff
Keyword(s):  
Antimicrobial Agents ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Chemical Constituents ◽  
Soil Conditions ◽  
Significant Activity ◽  
Daily Lives ◽  
Pests And Diseases ◽  
Wide Range ◽  
Rhodomyrtus Tomentosa

ABSTRACTRhodomyrtus tomentosa is a common wood, prevalent in areas with undemanding soil conditions and resistant toward pests and diseases. The plantcan be found in China, Taiwan, Philippines, Malaysia, Indonesia, and Vietnam. Literature and artwork indicate that R. tomentosa played an importantholistic role in the daily lives of several ancient cultures, providing medicinal benefits. R. tomentosa exhibits a wide spectrum of pharmacologicaleffects and has been used to treat colic diarrhea, wounds, heartburn, abscesses, gynecopathy, and as a pain killer. R. tomentosa was used in traditionalChinese medicine to treat urinary tract infection. 42 compounds have been isolated from this plant and structurally elucidated. They comprisephloroglucinol, flavonoid, terpenoid, anthracene glycoside, tannin, and other compounds. Rhodomyrtone, a member of the acylphloroglucinolsdemonstrated a significant activity against a wide range of Gram-positive bacteria. Rhodomyrtone exhibited both antimicrobial and anti-infectiveactivities. Several biological activities have been documented as antibacterial, antifungal, antimalarial, osteogenic, antioxidant, and anti-inflammatory.R. tomentosa has been studied extensively for alternative antimicrobial agents. Although rhodomyrtone exhibited potential activity with a very lowminimum inhibitory concentration value, the mechanisms of action of this compound are still unclear. Furthermore, toxicity studies on it extract tovalidate pharmacological activities are required.Keywords: Rhodomyrtus tomentosa, Kemunting, Phytochemical, Pharmacological, Biological activities, Chemical constituents.

Effect of consumption of a Mediterranean herb Crocus Sativus L. (Saffron) on health aspects: Evidence and Prospects

2021 ◽  
Vol 17 ◽  
Author(s):  
Ena Gupta ◽  
Priyanka Singh ◽  
Neha Mishra ◽  
Suman Devi
Keyword(s):  
Biological Activities ◽  
Wide Spectrum ◽  
Antioxidant Properties ◽  
Daily Intake ◽  
New Drugs ◽  
Crocus Sativus ◽  
Baked Goods ◽  
Wide Range ◽  
Yellow Orange ◽  
Crocus Sativus L

: Crocus sativus L. (Saffron) is a Mediterranean herb of the Iridaceae family. The dried stigmas of C. Sativa plant are processed to produce well-known spice saffron rich in secondary metabolites (safranal, crocetin, terpenes, crocins, picrocrocin, kaempferol and quercetin) with a wide range of important biological activities in curing many human diseases. Around the world, saffron is considered to be the most expensive spice, with an estimated annual production of around 300 tons per year. Therapeutic efficacies of saffron are proved through pharmacological studies and it is considered as a promising candidate with potentials for designing new drugs. In different food supplements, saffron is mainly used due to its antioxidant properties, intense flavour, aroma and luminous yellow-orange hue. Worldwide it is used in everything from confectioneries, liquors, cheeses, curries, soups, baked goods and meat dishes. This review is aimed to summarize the ethnomedicinal importance, phytochemistry and acceptable daily intake with a wide spectrum of pharmacological and therapeutic applications of saffron.

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