Synthesis, Docking, in silico ADMET and Pharmacological Evaluation of Some N-acetyl Pyrazole and Quinoline Conjugates

2020 ◽  
Vol 17 (8) ◽  
pp. 1015-1026
Author(s):  
Nargisbano Ayyub Peerzade ◽  
Shravan Yegu Jadhav ◽  
Raghunath Bhikaji Bhosale ◽  
Amol Anantrao Kulkarni ◽  
Bhushan Dnyandeo Varpe
Keyword(s):  
Antioxidant Activity ◽  
Ascorbic Acid ◽  
In Silico ◽  
Amylase Activity ◽  
Antimalarial Activity ◽  
In Silico Admet ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Almost All

Background: Pyrazolines are reported having anti-inflammatory, anti-oxidant and antidiabetic activities in the literature. Drugs like celecoxib, antipyrine, etc. are structurally similar to the designed compounds. Objectives: To synthesize and characterize N-acetyl pyrazole and quinoline conjugates and test them for Anti-inflammatory, Antioxidant, Antibacterial, Antiamylase and Antimalarial activities. Methods: A series of methoxy substituted quinoline based pyrazoline derivatives (2a-2j) were synthesized in good to excellent yield from corresponding quinoline chalcones (1a-1j). The synthesized compounds were characterized and screened for their in vitro anti-inflammatory, antioxidant, antiamylase, antibacterial and antimalarial activities. Docking and in silico ADMET studies were performed with PDB: 3LN1. Results: Compounds 2b, 2i and 2j showed significant anti-inflammatory activity as compared to standard sodium diclofenac. All compounds (2a-2j) showed excellent antioxidant activity for DPPH even more than standard ascorbic acid. Compounds 2e, 2f, 2h and 2i showed excellent antioxidant activity for NO. as compared to standard ascorbic acid. Compound 2f showed significant antioxidant activity for SOR. Almost all the compounds showed significant antibacterial as well as anti-amylase activity with few exceptions, whereas compounds 2f, 2h and 2j showed potent antimalarial activity. Conclusion: Compounds have shown good anti-inflammatory activities as compared with diclofenac. All the synthesized pyrazoline derivatives showed excellent anti-amylase activity as compared to standard acarbose. Also, compounds have shown good antioxidant antibacterial and antimalarial activities.

scholarly journals EVALUATION OF INVITRO ANTI-OXIDANT ACTIVITY OF MAGNOLIA CHAMPACA

2021 ◽  
Vol 6 (8) ◽  
pp. 73-77
Author(s):  
G.SAI SRUTHI ◽  
K. SPANDANA ◽  
RAMANJANEYULU K ◽  
HIMABINDHU J
Keyword(s):  
Antioxidant Activity ◽  
Ascorbic Acid ◽  
Leaf Extract ◽  
Ethanol Extract ◽  
In Vitro Assay ◽  
Vitro Assay ◽  
Soxhlet Apparatus ◽  
Dpph Method ◽  
Anti Oxidant

The aim of this article is to evaluate antioxidant activity of leaf extract of Magnolia champaca by using in vitro assay. Extraction was carried out with ethanol by using Soxhlet apparatus. The invitro antioxidant activity of ethanol extract has been investigated by 1, 1-diphenyl, 2-picryl–hydrazyl free radical (DPPH) method. The ethanol extract exhibited maximum antioxidant activity. The results have been compared with the standard ascorbic acid.

scholarly journals The synthesis and the antioxidant activity of 1-phenoxymethyl-4-aryl-5,6,7,8-tetrahydro-2a,4a,8a-triazacyclopenta[cd]azulene-3-carboxylic (or carbothionic) acid derivatives

Pharmacia ◽  
2021 ◽  
Vol 68 (1) ◽  
pp. 251-258
Author(s):  
Sergii Demchenko ◽  
Hanna Yeromina ◽  
Yulia Fedchenkova ◽  
Zinaida Ieromina ◽  
Vitaliy Yaremenko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Ascorbic Acid ◽  
Carboxylic Acid ◽  
In Silico ◽  
Pharmacokinetic Profile ◽  
High Antioxidant Activity ◽  
Pharmacological Screening

New 1-phenoxymethyl-4-aryl-5,6,7,8-tetrahydro-2а,4a,8a-triazacyclopenta[cd]azulene-3-carboxylic (or carbothionic) acid derivatives have been designed, synthesized and evaluated for their in vitro antioxidant activity under conditions of the artificial oxidative stress using ionol, ascorbic acid and α-tocopherol as the reference drugs. It has been found that 1-phenoxymethyl-4-aryl-5,6,7,8-tetrahydro-2а,4a,8a-triazacyclopenta[cd]azulene-3-carbothionic acid derivatives 9b, 9c, 9d, 9e, 9f, 9i and 1-phenoxymethyl-4-(41-chlorophenyl)-5,6,7,8-tetrahydro-2,2a,8-triazacyclopenta[cd]azulene-3-carboxylic acid phenylamide 10 reveal a high antioxidant activity and a good in silico pharmacokinetic profile. The data obtained allowed us to select the most promising objects from the substances synthesized for further pharmacological screening for the presence of the antioxidant activity in vivo.

Design, Synthesis and Pharmacological Evaluation of Gastro- Protective Anti-inflammatory Analgesic Agents based on Dual Oxidative Stress / Cyclooxygenase Inhibition

2020 ◽  
Vol 19 (3) ◽  
pp. 268-290 ◽  
Author(s):  
Monika Gaba ◽  
Sarbjot Singh ◽  
Chander Mohan ◽  
Richa Dhingra ◽  
Monika Chauhan ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Inhibitory Activity ◽  
Frap Assay ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Analgesic Activities ◽  
Cox 1

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) derived local generation of reactive oxygen species (ROS) plays a crucial role in the formation of gastric ulceration. Objective: Therefore, anti-inflammatory analgesics with potent antioxidant activity could be a potential therapeutic strategy for the treatment of pain and inflammatory disorders without gastrointestinal (GI) side effects. Methods: In an effort to develop gastroprotective analgesic and anti-inflammatory agents, a series of 2-methylamino-substituted-1H-benzo[d] imidazol-1-yl) (phenyl) methanone derivatives were synthesized and evaluated in vitro for cyclooxygenase (COX) inhibition as well as anti-oxidant potential by the FRAP assay. The compounds with significant in vitro COX-1/COX-2 inhibitory activity and antioxidant activity were further screened in vivo for their anti-inflammatory and analgesic activities. Moreover, the ulcerogenic potential of test compounds was also studied. To gain insight into the plausible mode of interaction of compounds within the active sites of COX-1 and COX-2, molecular docking simulations were performed. Results: Among the various synthesized molecules, most of the compounds showed good cyclooxygenase inhibitory activity and efficient antioxidant activity in FRAP assay. After preliminary and indicative in vitro assays, three compounds exhibited most significant antiinflammatory and analgesic activity with better gastric tolerability during their in vivo evaluation. Ligand interaction studies indicated highest dock score -43.05 of 1,2- disubstituted benzimidazole derivatives in comparison to the reference ligand -30.70. Overall studies provided us (2-((4-methoxyphenylamino) methyl) -1h-benzo [d] imidazol- 1-yl) (phenyl) methanone as a lead with potent gastro-protective anti-inflammatory and analgesic activities that can be used for future research. Conclusion: From the above results, it can be concluded that designing of multifunctional molecules with COX-1/COX-2 inhibitory and anti-oxidant activities could hold a great promise for further development of GI-safer NSAIDs.

Synthesis and Evaluation of Substituted Aryl Thiazoles With Antioxidant Potential as Gastro-sparing Anti-inflammatory Agents

2020 ◽  
Vol 17 (12) ◽  
pp. 1566-1578
Author(s):  
Akhil Bansal ◽  
Alka Bali ◽  
Ajitesh Balaini
Keyword(s):  
Antioxidant Activity ◽  
Ascorbic Acid ◽  
Reducing Power ◽  
Structural Features ◽  
Inflammatory Activity ◽  
Standard Group ◽  
Standard Drug ◽  
Rat Paw Edema ◽  
Anti Inflammatory

Background: NSAIDs are used as first-line drugs for the treatment of various inflammatory disorders. Chronic use of NSAIDs is known to be associated with gastrointestinal and renal toxicity. Local generation of reactive oxygen species finally resulting in cellular apoptosis is one of the accepted mechanisms for NSAID-induced toxicity. Objective: The objective of the present study was to design and synthesize a series of 2-methane sulfonamido substituted arylthiazole derivatives by including structural features of combined antiulcer and anti-inflammatory activity utilizing as the structural core, thiazole nucleus with potential for antioxidant effect. Methods: Compounds were designed based on three dimensional and field similarity studies. The synthesized compounds were evaluated for their anti-inflammatory activity in carrageenan-induced rat paw edema model. Rofecoxib and indomethacin were taken as standard drugs for comparison. The in vitro antioxidant activity was assessed in potassium ferricyanide reducing power (PFRAP) assay employing ascorbic acid as the standard drug. Results: The compounds 6 and 7 showed good anti-inflammatory activity comparable to the standard group and were also non ulcerogenic at the test doses. Compounds 1-7 displayed varying degrees of reducing power in the PFRAP) assay and the methanesulphonamido derivatives 4-7 showed the highest antioxidant activity (EC50 values 3.7-5.1 μmol/ml vs ascorbic acid 7.4 μmol/ml). Theoretical ADME profiling of the compounds based on selected physicochemical properties showed excellent compliance with Lipinski’s rule. Conclusion: A series of compounds have been designed and synthesized having dual antioxidant and anti-inflammatory activity with activities comparable to standard drugs.

Synthesis, In-Silico Potential Enzymatic target predictions, Pharmacokinetics, Toxicity, Anti-Microbial and Anti-Inflammatory Studies of Bis-(2-methylindolyl) methane Derivatives

2021 ◽  
Vol 17 ◽  
Author(s):  
Dnyaneshwar T Nagre ◽  
Suraj N. Mali ◽  
Bapu R. Thorat ◽  
Swapnali A. Thorat ◽  
Atul R. Chopade ◽  
...  
Keyword(s):  
In Silico ◽  
Salmonella Typhi ◽  
Fungal Species ◽  
Resonance Spectroscopy ◽  
Bacterial Strains ◽  
Standard Drug ◽  
Antibacterial And Antifungal Activities ◽  
In Silico Admet ◽  
Anti Inflammatory

Background: The bis(indolyl)methanes (BIMs) scaffold is being reported for wide varieties of pharmacological profiles including anti-bacterial, anti-proliferative, anti-cancer, cytotoxic, insecticidal, analgesic, antioxidant, and anti-inflammatory agents. Materials and Methods: A series of bis(indolyl)methanes have been synthesized using greener and new approach using the reaction of different substituted aldehydes and indole in presence of easily available and biodegradable base such as piperidine in acetic acid at room temperature and characterized with ultraviolet–visible spectrophotometry (UV–Vis or UV/Vis),Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy(NMR),etc. The antibacterial and antifungal activities were also carried out against Staphylococcus aureus (RCMB 000106) and Bacillis subtilis (RCMB 000107), as two Gram positive bacterial strains and Salmonella typhi and Escherichia coli (RCMB 000103), as two Gram negative bacterial strains. Fungal Species such as Candida Albicans, Penicillium chrysogenum, Aspergillus niger were also used for in-vitro antifungal evaluation. All our newly synthesized 14 compounds (4a-4n) were subjected for anti-inflammatory activity in-vitro and compared with known standard drug Aceclofenac. Results and Conclusions: Our newly synthesized compounds showed good to moderate antibacterial agents, in-silico ADMET and anti-inflammatory profiles. We hope that our current study would aid future developments of bis(indolyl)methanes as antibacterial and anti-inflammatory agents.

Synthesis of Novel Aryl (4-Aryl-1h-Pyrrol-3-Yl) (Thiophen-2-Yl) Meth-anone Derivatives: Molecular Modelling, In Silico Admet, Anti-Inflammatory and Anti-Ulcer Activities

2020 ◽  
Vol 19 ◽  
Author(s):  
MD Arif Pasha ◽  
Sumanta Mondal ◽  
Naresh Panigrahi
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
Active Site Residues ◽  
New Class ◽  
In Silico Admet ◽  
Sequential Addition ◽  
Anti Inflammatory ◽  
Cox 1 ◽  
Autodock 4.2

Background:: A series of novel aryl (4-aryl-1H-pyrrol-3-yl) (thiophen-2-yl) methanone derivatives was synthe-sized from sequential addition reaction with chalcones and toluenesulfonylmethyl isocyanide (TosMIC). Methods: The de-rivatives were screened against anti-inflammatory, anti-ulcer activities with an inhibition of 80.65% for PY-5 compound at 200mg/kg and inhibition of 77.5% for PY-1 compound at 200mg/kg. Active anti-inflammatory agents were subjected to in-vitro Cyclooxygenase (COX) inhibition assay. The interactions between the synthesized compounds and active site residues of proteins COX-1 (3N8Y), COX-2 (1PXX), H+/K+ ATPase (2XZB) were investigated by using molecular docking studies using autodock 4.2. Results and Conclusion:: In silico drug likeliness and toxicity prediction studies were carried by OSIRIS property explorer and admetSAR prediction tool which predicts that two compounds of PY-5 and PY-1 shows a new class of potential anti-inflammatory and anti-ulcer agents and serves as new anti-inflammatory and anti-ulcer drugs after further investigation.

α-Glucosidase Inhibition, Antioxidant and Docking Studies of Hydroxycoumarins and their Mono and Bis O-alkylated/acetylated Analogs

2018 ◽  
Vol 15 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Parvesh Singh ◽  
Nomandla Ngcoya ◽  
Ramgopal Mopuri ◽  
Nagaraju Kerru ◽  
Neha Manhas ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Catalytic Site ◽  
Docking Simulations ◽  
In Silico Docking ◽  
Anti Oxidant

Background: Diabetes Mellitus (DM) is a complex metabolic disease illustrated by abnormally high levels of plasma glucose or hyperglycaemia. Accordingly, several α-glucosidase inhibitors have been developed for the treatment of diabetes and other degenerative disorders. While, a coumarin ring has the privilege to represent numerous natural and synthetic compounds with a wide spectrum of biological activities e.g. anti-cancer, anti-HIV, anti-viral, anti-malarial, anti-microbial, anti-convulsant, anti-hypertensive properties. Besides this, coumarins have also shown potential to inhibit α-glucosidase leading to a generation of new promising antidiabetic agents. However, the testing of O-substituted coumarins for α-glucosidase inhibition has evaded the attention of medicinal chemists. Methods: For O-alkylation/acetylation reactions, the hydroxyl coumarins (A-B) initially activated by K2CO3 in dry DMF were reacted with variedly substituted haloalkanes at room temperature under nitrogen. The synthesized compounds were tested for their α-glucosidase (from Saccharomyces cerevisiae) inhibitory activity and anti-oxidant activity using DPPH radical scavenging activity. In silico docking simulations were conducted using CDocker module in DS (Accelrys) to explore the binding modes of the representative compounds in the catalytic site of α-glucosidase. Results: All the coumarin analogues (A1, B1, A2-A10, B2-B8) including their precursors (A-B) were evaluated for their in vitro α-glucosidase inhibition using acarbose as a standard inhibitor. All the mono O-alkylated coumarins (except A1) showed significant (p <0.05) α-glucosidase inhibition relative to the hydroxyl coumarin (A) with IC50 values ranging between 11.084±0.117 to 145.24± 29.22 µg/mL. Compound 7-(benzyloxy)-4, 5-dimethyl-2H-chromen-2-one (A9) bearing a benzyl group (Ph-CH2-) at position 7 showed a remarkable (p <0.05) increase in the activity (IC50 = 11.084±0.117 µg/mL), almost four-fold more than acarbose (IC50 = 40.578±5.999 µg/mL). The introduction of –NO2 group dramatically improved the anti-oxidant activity of coumarin, while the O-alkylation/acetylation decreased the activity. Conclusion: The present study describes the synthesis of functionalized coumarins and their evaluation for α-glucosidase inhibition and antioxidant activity under in vitro conditions. Based on IC50 data, the mono O-alkylated coumarins were observed to be stronger inhibitors of α-glucosidase with respect to their bis O-alkylated analogues. Coumarin (A9) bearing O-benzyloxy group displayed the strongest α-glucosidase inhibition, even higher than the standard inhibitor acarbose. The coumarin (A10) bearing –NO2 group showed the highest anti-oxidant activity amongst the synthesized compounds, almost comparable to the ascorbic acid. Finally, in silico docking simulations revealed the role of hydrogen bonding and hydrophobic forces in locking the compounds in catalytic site of α-glucosidase.

Red Grape Polyphenol Oral Administration improves Immune Response in Women Affected by Nickel-Mediated Allergic Contact Dermatitis

2020 ◽  
Vol 20 ◽  
Author(s):  
Thea Magrone ◽  
Emilio Jirillo ◽  
Manrico Magrone ◽  
Matteo Antonio Russo ◽  
Paolo Romita ◽  
...  
Keyword(s):  
Contact Dermatitis ◽  
Oral Administration ◽  
Allergic Contact Dermatitis ◽  
Laboratory Data ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Red Grape ◽  
Allergic Contact ◽  
Drop Outs

Background: Our previous findings demonstrated that in vitro supplementation of polyphenols, extracted from seeds of red grape (Nero di Troia cultivar), to peripheral lymphomonocytes from patients affected by allergic contact dermatitis (ACD) to nickel (Ni) could reduce release of pro-inflammatory cytokines and nitric oxide (NO), while increasing levels of interleukin (IL)-10, an anti-inflammatory cytokine. Objective: To assess whether an intervention with oral administration of polyphenols leads to a reduction of peripheral biomarkers in ACD patients. Method: At T0, 25 patients affected by ACD to Ni were orally administered with 300 mg polyphenols prodie extracted from seeds of red grape (Nero di Troia cultivar) (NATUR-OX®) for 3 months (T1). Other 25 patients affected by ACD to Ni received placebo only for the same period of time. Serum biomarkers were analyzed at T0 and T1. In both groups seven drop outs were recorded. Result: At T1 in comparison to T0, in treated patients, values of IFN-γ, IL-4, IL-17, PTX3 and NO decreased, while IL-10 levels increased when compared with T0 values. Conversely, in placebo-treated patients no modifications of biomarkers were evaluated at T1. Conclusion: Present laboratory data rely on the anti-oxidant, anti-inflammatory and anti-allergic properties of polyphenols.

Virtual Screening, Molecular docking and in-silico ADME-Tox analysis for identification of potential main protease (Mpro) enzyme inhibitors

2020 ◽  
Vol 18 ◽  
Author(s):  
Debadash Panigrahi ◽  
Ganesh Prasad Mishra
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Data Bank ◽  
Future Research ◽  
Reference Compound ◽  
Unexpected Death ◽  
Main Protease ◽  
In Silico Admet

Objective:: Recent pandemic caused by SARS-CoV-2 described in Wuhan China in December-2019 spread widely almost all the countries of the world. Corona virus (COVID-19) is causing the unexpected death of many peoples and severe economic loss in several countries. Virtual screening based on molecular docking, drug-likeness prediction, and in silico ADMET study has become an effective tool for the identification of small molecules as novel antiviral drugs to treat diseases. Methods:: In the current study, virtual screening was performed through molecular docking for identifying potent inhibitors against Mpro enzyme from the ZINC library for the possible treatment of COVID-19 pandemic. Interestingly, some compounds are identified as possible anti-covid-19 agents for future research. 350 compounds were screened based on their similarity score with reference compound X77 from ZINC data bank and were subjected to docking with crystal structure available of Mpro enzyme. These compounds were then filtered by their in silico ADME-Tox and drug-likeness prediction values. Result:: Out of these 350 screened compounds, 10 compounds were selected based on their docking score and best docked pose in comparison to the reference compound X77. In silico ADME-Tox and drug likeliness predictions of the top compounds were performed and found to be excellent results. All the 10 screened compounds showed significant binding pose with the target enzyme main protease (Mpro) enzyme and satisfactory pharmacokinetic and toxicological properties. Conclusion:: Based on results we can suggest that the identified compounds may be considered for therapeutic development against the COVID-19 virus and can be further evaluated for in vitro activity, preclinical, clinical studies and formulated in a suitable dosage form to maximize their bioavailability.

scholarly journals Chemical Composition, In Vitro and In Silico Antioxidant Potential of Melissa officinalis subsp. officinalis Essential Oil

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1081
Author(s):  
Matilda Rădulescu ◽  
Călin Jianu ◽  
Alexandra Teodora Lukinich-Gruia ◽  
Marius Mioc ◽  
Alexandra Mioc ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Chemical Composition ◽  
Essential Oil ◽  
In Silico ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Inhibitory Effect ◽  
Melissa Officinalis ◽  
Β Carotene

The investigation aimed to study the in vitro and in silico antioxidant properties of Melissa officinalis subsp. officinalis essential oil (MOEO). The chemical composition of MOEO was determined using GC–MS analysis. Among 36 compounds identified in MOEO, the main were beta-cubebene (27.66%), beta-caryophyllene (27.41%), alpha-cadinene (4.72%), caryophyllene oxide (4.09%), and alpha-cadinol (4.07%), respectively. In vitro antioxidant properties of MOEO have been studied in 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging, and inhibition of β-carotene bleaching assays. The half-maximal inhibitory concentration (IC50) for the radical scavenging abilities of ABTS and DPPH were 1.225 ± 0.011 μg/mL and 14.015 ± 0.027 μg/mL, respectively, demonstrating good antioxidant activity. Moreover, MOEO exhibited a strong inhibitory effect (94.031 ± 0.082%) in the β-carotene bleaching assay by neutralizing hydroperoxides, responsible for the oxidation of highly unsaturated β-carotene. Furthermore, molecular docking showed that the MOEO components could exert an in vitro antioxidant activity through xanthine oxidoreductase inhibition. The most active structures are minor MOEO components (approximately 6%), among which the highest affinity for the target protein belongs to carvacrol.

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