scholarly journals An Improved Synthesis of Key Intermediate to the Formation of Selected Indolin-2-Ones Derivatives Incorporating Ultrasound and Deep Eutectic Solvent (DES) Blend of Techniques, for Some Biological Activities and Molecular Docking Studies

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1118 ◽  
Author(s):  
Mohd Imran ◽  
Md. Afroz Bakht ◽  
Abida Khan ◽  
Md. Tauquir Alam ◽  
El Hassane Anouar ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Biological Activities ◽  
Deep Eutectic Solvent ◽  
Docking Studies ◽  
Dft Theory ◽  
Standard Drug ◽  
Anti Inflammatory ◽  
The Stability ◽  
Multistep Reaction ◽  
Good Agreement

We have developed a new idea to synthesize a key intermediate molecule by utilizing deep eutectic solvent (DES) and ultrasound in a multistep reaction to ensure process cost-effectiveness. To confirm the stability of reagents with DES, electronic energies were calculated at the B3LYP/6-31+G(d,p) level of theory. DES stabilized the reagents mainly due to strong intermolecular hydrogen bonding. Key intermediate (3) and final compounds (4a–n) were synthesized in a higher yield of 95% and 80%–88%, respectively. Further, final compounds (4a–n) were assessed for their anti-inflammatory, analgesic, ulcerogenic, and lipid peroxidation. The compounds 4f, 4g, 4j, 4l, and 4m showed good anti-inflammatory activity, while 4f, 4i, and 4n exhibited very good analgesic activity as compared to the standard drug. The ulcerogenicity of selected compounds was far less than the indomethacin. The ligands had also shown a good docking score (4f = −6.859 kcal/mol and 4n = −7.077 kcal/mol) as compared to control indomethacin (−6.109 kcal/mol) against the target protein COX-2. These derivatives have the potential to block this enzyme and can be used as NSAID. The state-of-art DFT theory was used to validate the lipid peroxidation mechanism of the active compounds which was in good agreement with the variations of BDEs and IP of the tested compounds.

scholarly journals An Improved Synthesis of Key Intermediate to the Formation of Selected Indolin-2-ones Derivatives Incorporating Ultrasound and Deep Eutectic Solvent (DES) Blend of Techniques, for Some Biological Activities and Molecular Docking Studies

Proceedings ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 8
Author(s):  
Mohd Imran ◽  
Md. AfrozBakht ◽  
Abida Khan ◽  
Md. Tauquir Alam ◽  
Anouar El Hassane ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Biological Activities ◽  
Deep Eutectic Solvent ◽  
Cost Effective ◽  
Docking Studies ◽  
Dft Theory ◽  
Standard Drug ◽  
Anti Inflammatory ◽  
Multistep Reaction ◽  
Good Agreement

We have developed a new idea to synthesize key intermediate molecule by utilizing deep eutectic solvent (DES) and ultrasound in a multistep reaction to ensure process cost-effective. Key intermediate (3) and final compounds (4a–n) were synthesized in a higher yield of 95% and 80–88% respectively. Further, final compounds (4a–n) were assessed for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation. The compounds 4f, 4g, 4j, 4l, and 4m showed good anti-inflammatory activity, while 4f, 4i, and 4n exhibited very good analgesic activity as compared to the standard drug. The ulcerogenicity of selected compounds was far less than the indomethacin. The ligands had also shown a good docking score (4f = −6.859 and 4n = −7.077) as compared to control indomethacin (−6.109).State-of-art DFT theory was used to validate the lipid peroxidation mechanism of the active compounds which was in good agreement with the variations of BDEs and IP of the tested compounds.

Design, Synthesis, Characterization and in silico molecular docking studies and in vivo anti-inflammatory Activity of Pyrazoline clubbed Thiazolinone Derivatives

2020 ◽  
Vol 17 ◽  
Author(s):  
Deepak Kumar Singh ◽  
Mayank Kulshreshtha ◽  
Yogesh Kumar ◽  
Pooja A Chawla ◽  
Akash Ved ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Biological Activities ◽  
Inflammatory Activity ◽  
Standard Drug ◽  
Docking Score ◽  
Chemical Structures ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

scholarly journals Synthesis, Molecular Modelling and Biological Evaluation of Novel Pyrimidine Derivatives as Anti-inflammatory Agents

2020 ◽  
pp. 49-67
Author(s):  
Naglaa Mohamed Ahmed ◽  
Shahira Nofal ◽  
Samir Mohamed Awad
Keyword(s):  
Docking Studies ◽  
Biological Evaluation ◽  
Inflammatory Activity ◽  
Pyrimidine Derivatives ◽  
Reference Drug ◽  
Rat Paw Edema ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1 ◽  
Good Agreement

Aim: As part of ongoing studies in developing new anti-inflammatory agents, 2-thioxo-1,2,3,4-tetrahydropyrimidine derivative 1 was synthesized by direct Biginelli condensation and used for the synthesis of novel series of  pyrimidin-2-thione derivatives  (2a-d to 7a-b). Materials and Methods: All compounds were examined for their anti-inflammatory activity using the carrageenan-induced rat paw edema assay in comparison to ibuprofen, as a reference drug. Molecular docking studies were carried out using SYBLYL-X v.2.1 software. Study Design: A series of pyrimidine derivatives were synthesized by a simple and available method leads to a molecule of promising anti-inflammatory activity, the docking studies show good agreement with anti-inflammatory results. Future researches are recommended to assure the importance of these new derivatives for various applications. Place and Duration of Study: Pharmaceutical Organic Chemistry Department and Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt, between February 2018 and March 2019. Results: Compounds showed 61 to 86% anti-inflammatory activity where-as ibuprofen showed 69% activity. Compounds 2a, 2b, 2c, 2d, 3a, 3b, 3c, 3d, 7a, 7b induced strong anti-inflammatory activity, comparable with that of ibuprofen, they showed significantly difference at 4h post-carrageenan. Compound 3c (86%) showed the best result of edema inhibition in rats. Moreover, compounds 1, 2c and 3c were subjected to in vitro enzyme assay investigations against COX-1 and COX-2. All tested compounds showed higher potency towards COX-2 over COX-1. Compound 3c realized higher potency towards COX-2 (IC50= 0.046 μM) than compounds 1(IC50= 0.21 μM) and 2c (IC50=0.11 μM) as well as ibuprofen (IC50= 43.628 μM). Structure-activity relationship (SAR) has been discussed. Conclusion: A series of pyrimidine derivatives were synthesized by a simple and available method gave a molecule of promising anti-inflammatory activity, the docking studies showed good agreement with anti-inflammatory results.

scholarly journals Identification of Bioactive Phytoconstituents from the Plant Euphorbia hirta as Potential Inhibitor of SARS-CoV-2: an In-Silico Approach

2021 ◽  
Vol 12 (2) ◽  
pp. 1385-1396
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Biological Activities ◽  
Specific Treatment ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Euphorbia Hirta ◽  
Main Protease

Currently, the entire globe is under the deadliest pandemic of Covid-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). At present, no specific treatment is available to combat COVID-19 infection. Euphorbia hirta (Euphorbiaceae) have been reported for a variety of biological activities, including antiviral. The present investigation aimed to identify potential phytoconstituents of the plant E. hirta from the category flavonoids and coumarins against the SARS-CoV-2 using in silico approach. The molecular docking studies were performed using two different targets of SARS-CoV-2, namely Main protease (Mpro; PDB ID: 6M2N) and RNA-dependent RNA polymerase (RdRp; PDB ID: 7BW4). Based on the molecular docking study in comparison with standard drug, four compounds, namely Euphrobianin, Quercetin, 3-o-alpha-rhamnoside, Isoquercitrin, and rutin, were screened against the target Mpro. Three phytoconstituents, euphorbianin, myricetin, and rutin, were screened against the target RdRp. In the in silico toxicity studies of screened phytoconstituents, except myrectin all were predicted safe. Results of euphorbianin and rutin were found more interesting as both compounds had high binding affinity against both targets. Finally, we want to conclude that euphrobianin, quercetin 3-o-alpha-rhamnoside, isoquercitrin, and rutin could be further explored rapidly as they may have the potential to fight against COVID-19.

scholarly journals Hepatoprotective activity against acetaminophen-induced liver dysfunction and GC-MS profiling of a brown algae Sargassum ilicifolium

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Khan Hira ◽  
Hafiza Farhat ◽  
Nida Sohail ◽  
Madeeha Ansari ◽  
Jehan Ara ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Liver Dysfunction ◽  
Liver Toxicity ◽  
Biological Activities ◽  
Intraperitoneal Administration ◽  
Halogenated Hydrocarbons ◽  
Hexane Fraction ◽  
Drug Induced ◽  
Standard Drug ◽  
Soluble Fractions

Abstract Background Drug-induced hepatotoxicity is one of the most important causes of liver dysfunction. Acetaminophen (paracetamol) an analgesic-antipyretic drug is generally considered safe but its overdose may cause liver toxicity. Marine macro-algae (seaweeds) especially brown seaweeds possess unique biological activities including hepatoprotective potential. The current study focused on the hepatoprotective effect of different solvent fractions of Sargassum ilicifolium and characterization of its n-hexane soluble fraction. Methods The ethanol extract (20 g) of S. ilicifolium was mixed with solvents of increasing polarity, starting with n-hexane followed by chloroform and methanol. All three (n-hexane, chloroform and methanol) soluble fractions were administered to the rats at dose of 150 mg/kg, b.w. Intraperitoneal administration of acetaminophen (600 mg/kg b.w.) to rats was used to cause liver injury. The hepatic damage was evaluated by liver markers enzymes; aspartate aminotransferases (AST), alanine aminotransferases (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin along with other metabolites i.e., triglycerides, cholesterol, urea, glucose and creatinine. Lipid peroxidation and glutathione and were estimated in liver tissue. n-Hexane fraction was subjected to GC-MS analysis in order to identify potent compounds. Results The oral administration of n-hexane and methanol soluble fractions reduced the acetaminophen-augmented liver marker enzymes ALT, AST, ALP, LDH, along with bilirubin, urea, creatinine, glucose and triglycerides. The n-hexane and methanol soluble fractions also improved hepatic antioxidant level via enhancing hepatic glutathione and reversing lipid peroxidation. GC-MS spectroscopy of n-hexane fraction of S. ilicifolium revealed the presence of some new compounds. Among them, fatty acids were found to be in highest concentration followed by halogenated hydrocarbons, benzene derivatives, and sterols. Fatty acid in seaweed may be one of the factors for hepatoprotection from drug-induced hepatotoxicity. Conclusion From the results, it is evident that n-hexane and methanol soluble fractions of S. ilicifolium have the ability to protect the liver against toxicity, which is comparable with silymarin used as a standard drug. Sargassum ilicifolium contains bioactive compounds with pharmaceutical importance.

scholarly journals Heterocycles 48. Synthesis, Characterization and Biological Evaluation of Imidazo[2,1-b][1,3,4]Thiadiazole Derivatives as Anti-Inflammatory Agents

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2425 ◽  
Author(s):  
Anamaria Cristina ◽  
Denisa Leonte ◽  
Laurian Vlase ◽  
László Bencze ◽  
Silvia Imre ◽  
...  
Keyword(s):  
Side Effects ◽  
Inflammatory Diseases ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Standard Drug ◽  
Rat Paw Edema ◽  
Thiadiazole Derivatives ◽  
Cox 2 ◽  
Anti Inflammatory

Non-steroidal anti-inflammatory drugs (NSAIDs) are an important pharmacological class of drugs used for the treatment of inflammatory diseases. They are also characterized by severe side effects, such as gastrointestinal damage, increased cardiovascular risk and renal function abnormalities. In order to synthesize new anti-inflammatory and analgesic compounds with a safer profile of side effects, a series of 2,6-diaryl-imidazo[2,1-b][1,3,4]thiadiazole derivatives 5a–l were synthesized and evaluated in vivo for their anti-inflammatory and analgesic activities in carrageenan-induced rat paw edema. Among all compounds, 5c showed better anti-inflammatory activity compared to diclofenac, the standard drug, and compounds 5g, 5i, 5j presented a comparable antinociceptive activity to diclofenac. None of the compounds showed ulcerogenic activity. Molecular docking studies were carried out to investigate the theoretical bond interactions between the compounds and target, the cyclooxygenases (COX-1/COX-2). The compound 5c exhibited a higher inhibition of COX-2 compared to diclofenac.

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 One-Pot Synthesis of Novel Furochromone and Oxazocine Derivatives as Promising Antitumor Agents with Their Molecular Docking Studies

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Rita M. Borik
Keyword(s):  
Molecular Docking ◽  
Antitumor Agents ◽  
Docking Studies ◽  
One Pot ◽  
Simple Method ◽  
Standard Drug ◽  
Molecular Docking Studies ◽  
Benzoic Acid Derivatives ◽  
Derivatives Of ◽  
Good Agreement

One-pot efficient synthesis of novel chromone derivatives 4a–h and that of 5a–h were described in a simple method via four-component reaction between furochromone carbaldehyde, amine, isocyanate derivatives, and benzoic acid derivatives or nicotinic acid, respectively. Also, oxazocine derivatives 7a, b were prepared via reaction of visnagine carbaldehyde, ethyl acetoacetate and isocyanate derivatives 2a, b. The obtained derivatives of novel furochromone and oxazocine derivatives were evaluated as promising antitumor agents against panel of two human cell lines, hepatocellular carcinoma (HEPG2) and breast carcinoma (MCF7). The antitumor results suggested that furochromone derivatives 5a–h have activity against MCF7 in comparison with doxorubicin as the standard drug. Furthermore, the molecular docking studies of these novel derivatives of furochromone and oxazocine showed good agreement with the biological results when their binding pattern and affinity towards the active site of EGFR was investigate.

scholarly journals Pyrazoles and Pyrazolines as Anti-Inflammatory Agents

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3439
Author(s):  
Martha Mantzanidou ◽  
Eleni Pontiki ◽  
Dimitra Hadjipavlou-Litina
Keyword(s):  
Lipid Peroxidation ◽  
Hydrophobic Interactions ◽  
Halogen Bond ◽  
Biological Activities ◽  
Preliminary Test ◽  
Docking Studies ◽  
Lipoxygenase Inhibitor ◽  
Wide Range ◽  
Inhibit Lipid Peroxidation

The five-membered heterocyclic group of pyrazoles/pyrazolines plays important role in drug discovery. Pyrazoles and pyrazolines present a wide range of biological activities. The synthesis of the pyrazolines and pyrazole derivatives was accomplished via the condensation of the appropriate substituted aldehydes and acetophenones, suitable chalcones and hydrazine hydrate in absolute ethanol in the presence of drops of glacial acetic acid. The compounds are obtained in good yields 68–99% and their structure was confirmed using IR, 1H-NMR, 13C-NMR and elemental analysis. The novel derivatives were studied in vitro for their antioxidant, anti-lipid peroxidation (AAPH) activities and inhibitory activity of lipoxygenase. Both classes strongly inhibit lipid peroxidation. Compound 2g was the most potent lipoxygenase inhibitor (IC50 = 80 µM.) The inhibition of the carrageenin-induced paw edema (CPE) and nociception was also determined, with compounds 2d and 2e being the most potent. Compound 2e inhibited nociception higher than 2d. Pyrazoline 2d was found to be active in a preliminary test, for the investigation of anti-adjuvant-induced disease (AID) activity. Pyrazoline derivatives were found to be more potent than pyrazoles. Docking studies of the most potent LOX inhibitor 2g highlight hydrophobic interactions with VAL126, PHE143, VAL520 and LYS526 and a halogen bond between the chlorine atom and ARG182.

scholarly journals Molecular Docking Studies, Analgesic and Anti-inflammatory Screening of Some Novel Quinazolin-4-one Derivatives

2021 ◽  
Vol 33 (5) ◽  
pp. 1058-1062
Author(s):  
K.N. Rajini Kanth ◽  
Ch. Jaswanth Kumar ◽  
D. Eswar Tony ◽  
Sk. Munwar ◽  
Rama Rao Nadendla ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Standard Drug ◽  
Molecular Docking Studies ◽  
Hydrogen Bonding Interactions ◽  
Anti Inflammatory ◽  
Pharmacological Screening ◽  
Analgesic Activities ◽  
Cox 2 Inhibitors ◽  
Further Development

Molecular docking studies was performed on 20 analogous novel quinazolin-4-one derivatives as cox-2 inhibitors using glide tool of maestro 11.4 application of Schrodinger software. Anti-inflammatory and analgesic activities were further evaluated for the compounds. Based on docking studies, the binding affinity of QZN-16 was found to be -10.32 kcal/mol. In order to understand the significance of R-substituents on the quinazoline-4-one nucleus, the findings of hydrogen bonding interactions between designated ligands with binding site region of 4cox were studied. The ligands which are having high docking score were subjected to pharmacological screening. The compound QZN-16 has shown analgesic and anti-inflammatory activity at a dose level of 50 and 100 mg/kg body weight, respectively when compared with standard drug indomethacin. The newly designed quinazoline-4-one derivatives may serve as lead molecules for further development.

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