ROS Inhibitory Activity and Cytotoxicity Evaluation of Benzoyl, Acetyl, Alkyl Ester, and Sulfonate Ester Substituted Coumarin Derivatives

2020 ◽  
Vol 16 (8) ◽  
pp. 1099-1111
Author(s):  
Uzma Salar ◽  
Khalid M. Khan ◽  
Almas Jabeen ◽  
Aisha Faheem ◽  
Farwa Naqvi ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Antiinflammatory Drug ◽  
Vital Role ◽  
Alkyl Ester ◽  
Flufenamic Acid ◽  
Coumarin Derivatives ◽  
Inflammatory Disorders ◽  
Enhanced Chemiluminescence ◽  
Anti Inflammatory ◽  
Sulfonate Ester

Background: A number of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, indomethacin, ibuprofen, flufenamic acid, and phenylbutazone are being clinically used to treat inflammatory disorders. These NSAIDs are associated with serious side effects such as gastric ulceration, nephrotoxicity, and bleeding. Therefore, the identification of potent and safe therapy for inflammatory disorders is still of great interest to the medicinal chemist. Methods: A series of varyingly substituted benzoyl, acetyl, alkyl ester, and sulfonate ester substituted coumarins 1-64 were screened for the inhibition of ROS, generated from zymosan activated whole blood phagocytes, using luminol-enhanced chemiluminescence technique. Results: Among all tested compounds, 8 (IC50 = 65.0 ± 3.1 μM), 24 (IC50 = 41.8 ± 1.5 μM), 26 (IC50 = 10.6 ± 2.8 μM), 28 (IC50 = 20.9 ± 1.5 μM), and 41 (IC50 = 4.6 ± 0.3 μM) showed good anti- inflammatory potential as compared to standard antiinflammatory drug ibuprofen (IC50 = 54.3 ± 1.9 μM). Specifically, compounds 24, 26, 28, and 41 showed superior activity than standard antiinflammatory drug. Furthermore, compounds 12 (IC50 = 219.0 ± 1.4 μM), 14 (IC50 = 216.5 ± 6.2 μM), 16 (IC50 = 187.4 ± 2.2 μM), and 20 (IC50 = 196.2 ± 2.0 μM) showed moderate ROS inhibitory activity. Limited SAR study revealed that the hydroxy-substituted compound showed better ROS inhibition potential in case of 3-benzoyl and 3-ethylester coumarin derivatives. Whereas, chloro substitution was found to be important in case of 3-acetyl coumarin derivatives. Similarly, in case of sulfonate ester, chloro, and nitro groups especially at positions -4 and -3 of ring “R” played vital role in ROS inhibition. Furthermore, cytotoxicity of all active compounds was also checked on NIH-3T3 cell line. Compounds 12, 14, and 20 were found to be non-cytotoxic. Whereas, 8, 16, 24, 26, 28, and 41 were found to be very weak cytotoxic as compared to standard cycloheximide (IC50 = 0.13 ± 0.02 μM). Conclusion: Identified ROS inhibitors offer the possibility of additional modifications that could give rise to lead structures for further research in order to obtain more potent, and safer antiinflammatory agent.

Diversified Thiazole Substituted Coumarins and Chromones as Non- Cytotoxic ROS and NO Inhibitors

2020 ◽  
Vol 17 (5) ◽  
pp. 547-555
Author(s):  
Uzma Salar ◽  
Khalid Mohammed Khan ◽  
Almas Jabeen ◽  
Shafquat Hussain ◽  
Aisha Faheem ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Flufenamic Acid ◽  
Future Research ◽  
Active Compounds ◽  
Inflammatory Disorders ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Acidic Nature ◽  
Nih 3T3 ◽  
Substituted Coumarins

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, aspirin, indomethacin, flufenamic acid and phenylbutazone are used to treat most of the inflammatory disorders. These NSAIDs are also associated with serious side effects including gastric ulceration, nephrotoxicity, and bleeding, mainly due to acidic nature. Hence, there is a need to identify highly potent and safer treatment for inflammatory disorders. Methods: Herein, synthetic hydrazinyl thiazole substituted coumarins and chromones 1-48 were evaluated for ROS inhibitory activity. ROS were generated from zymosan activated whole blood phagocytes. Results: Among all tested compounds, compounds 1 (IC50 = 38.3 ± 7.1 μM), 2 (IC50 = 5.7 ± 0.2 μM), 5 (IC50 = 28.3 ± 3.5 μM), 23 (IC50 = 12.5 ± 3.1 μM), 27 (IC50 = 32.8 ± 1.1 μM), 39 (IC50 = 20.2 ± 1.6 μM), and 42 (IC50 = 43.2 ± 3.8 μM) showed potent ROS inhibition as compared to standard ibuprofen (IC50 = 54.3 ± 1.9 μM). Whereas, compounds 3 (IC50 = 134.7 ± 1.0 μM), 16 (IC50 = 75.4 ± 7.2 μM), 24 (IC50 = 102.4 ± 1.0 μM), and 31 (IC50 = 86.6 ± 1.5 μM) were found to be moderately active. Compounds 1, 2, 5, 23, 27, 39, and 42, having potent ROS inhibitory activity were also screened for their nitric oxide (NO) inhibition. Cytotoxicity was also checked for all active compounds on NIH-3T3 cell line. Cyclohexamide (IC50 = 0.13 ± 0.02 μM) was used as standard. Conclusion: Identified active compounds from these libraries may serve as lead candidates for future research in order to obtain a more potent, and safer anti-inflammatory agent.

Pharmacologically potentials of different substituted coumarin derivatives

2019 ◽  
Author(s):  
Chem Int
Keyword(s):  
Benzene Ring ◽  
Bioactive Compounds ◽  
Biological Activities ◽  
Pharmacological Properties ◽  
Coumarin Derivatives ◽  
Wide Range ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Coumarin Compounds

Coumarin and its derivatives are widely spread in nature. Coumarin goes to agroup as benzopyrones, which consists of a benzene ring connected to a pyronemoiety. Coumarins displayed a broad range of pharmacologically useful profile.Coumarins are considered as a promising group of bioactive compounds thatexhibited a wide range of biological activities like anti-microbial, anti-viral,antiparasitic, anti-helmintic, analgesic, anti-inflammatory, anti-diabetic, anticancer,anti-oxidant, anti-proliferative, anti-convulsant, and antihypertensiveactivities etc. The coumarin compounds have immense interest due to theirdiverse pharmacological properties. In particular, these biological activities makecoumarin compounds more attractive and testing as novel therapeuticcompounds.

Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder

2020 ◽  
Vol 28 (2) ◽  
pp. 360-376 ◽  
Author(s):  
Atefeh Amiri ◽  
Maryam Mahjoubin-Tehran ◽  
Zatollah Asemi ◽  
Alimohammad Shafiee ◽  
Sarah Hajighadimi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Antioxidant Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Inflammatory Disorder ◽  
Inflammatory Disorders ◽  
Therapeutic Modalities ◽  
Anti Cancer ◽  
Current Therapies ◽  
Anti Inflammatory

: Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.

Development, Pre-clinical Investigation and Histopathological Evaluation of Metronidazole Loaded Topical Formulation for Treatment of Skin Inflammatory disorders

2020 ◽  
Vol 10 ◽  
Author(s):  
Divya Thakur ◽  
Gurpreet Kaur ◽  
Sheetu Wadhwa ◽  
Ashana Puri
Keyword(s):  
Ex Vivo ◽  
Clinical Investigation ◽  
In Vivo Studies ◽  
Tween 20 ◽  
Inflammatory Disorders ◽  
Rat Paw Edema ◽  
Ex Vivo Permeation ◽  
Permeation Studies ◽  
Anti Inflammatory

Background: Metronidazole (MTZ) is an anti-oxidant and anti-inflammatory agent with beneficial therapeutic properties. The hydrophilic nature of molecule limits its penetration across the skin. Existing commercial formulations have limitations of inadequate drug concentration present at target site, which requires frequent administration and poor patient compliance. Objective: The aim of current study was to develop and evaluate water in oil microemulsion of Metronidazole with higher skin retention for treatment of inflammatory skin disorders. Methods: Pseudo ternary phase diagrams were used in order to select the appropriate ratio of surfactant and co-surfactant and identify the microemulsion area. The selected formulation consisted of Capmul MCM as oil, Tween 20 and Span 20 as surfactant and co-surfactant, respectively, and water. The formulation was characterized and evaluated for stability, Ex vivo permeation studies and in vivo anti-inflammatory effect (carrageenan induced rat paw edema, air pouch model), anti-psoriatic activity (mouse-tail test). Results: The particle size analyses revealed average diameter and polydispersity index of selected formulation to be 16 nm and 0.373, respectively. The results of ex vivo permeation studies showed statistically higher mean cumulative amount of MTZ retained in rat skin from microemulsion i.e. 21.90 ± 1.92 μg/cm2 which was 6.65 times higher as compared to Marketed gel (Metrogyl gel®) with 3.29 ± 0.11 μg/cm2 (p<0.05). The results of in vivo studies suggested the microemulsion based formulation of MTZ to be similar in efficacy to Metrogyl gel®. Conclusion: Research suggests efficacy of the developed MTZ loaded microemulsion in treatment of chronic skin inflammatory disorders.

scholarly journals In Vitro α-Amylase and Protein Glycation Inhibitory Activity of the Aqueous Extract of Flueggea leucopyrus Willd

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Vishmi Sachindra Thrikawala ◽  
Srianthie A. Deraniyagala ◽  
Chamira Dilanka Fernando ◽  
Dinusha Nishani Udukala
Keyword(s):  
Aqueous Extract ◽  
Diabetic Complications ◽  
Inhibitory Activity ◽  
Radical Scavenging ◽  
Vital Role ◽  
Protein Glycation ◽  
Total Phenolic ◽  
Chronic Hyperglycemia ◽  
Body Tissues

There is much interest in plant-based medicine with antidiabetic and antiglycation properties. Chronic hyperglycemia plays a vital role in the development of long-term diabetic complications by inducing protein glycation and the gradual formation of advanced glycation end products (AGEs) in various body tissues. The main objectives of this study were to investigate the aqueous extract of the whole plant of Flueggea leucopyrus Willd (FLAE), a medicinal plant used in traditional medicine in Sri Lanka for its in vitro α-amylase inhibitory activity and its inhibitory potential on the formation of AGEs. α-Amylase inhibitory activity determined by 3,5-dinitrosalicylic acid method revealed that FLAE possesses 29%–91% inhibitory activity at a concentration range of 2.5–400 μg/mL, respectively. Nonenzymatic protein glycation inhibitory capacity assessed by bovine serum albumin-fructose fluorescence spectrometric assay showed that FLAE at 15.6–250.0 μg/mL inhibited AGE formation by 0.9%–98%, respectively. Radical scavenging ability of FLAE using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and total phenolic and flavonoid contents of FLAE were also determined. This study shows that Flueggea leucopyrus Willd not only inhibits α-amylase enzyme, which is known to break starch to glucose, but also inhibits the formation of AGEs, which occur due to chronic hyperglycemia that leads to the onset of diabetic complications.

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