scholarly journals Sintesis Senyawa Vanilil Metil Keton dan Uji Aktivitas Antiinflamasi terhadap Enzim COX-1 dan COX-2 melalui Analisis In Silico

ALCHEMY ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 1-11
Author(s):  
Khoirotul Ummah ◽  
Robby Gus Mahardika ◽  
Ana Mardliyah
Keyword(s):  
In Silico ◽  
Methyl Ketone ◽  
Aerobic Condition ◽  
In Silico Analysis ◽  
Inflammatory Activity ◽  
Wacker Oxidation ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Silico Analysis ◽  
Cox 1

This study reports the synthesis of vanillyl methyl ketone from eugenol through Wacker oxidation and anti-inflammatory activity test toward COX-1 and COX-2 through in silico analysis. Wacker oxidation process was catalyzed by PdCl2 and CuCl2 using DMF solvent under the aerobic condition at room temperature for 48 hours. The product of the synthesis was purified by column chromatography and was characterized by NMR, IR, and MS spectroscopy. Characterization by spectroscopic methods showed that vanillyl methyl ketone was formed with a yield of 45% and vanillin (3%) was produced as a by-product. The anti-inflammatory activity of vanillyl methyl ketone was carried out by molecular docking toward   COX-1 and COX-2 obtained from PDB. The analysis showed that the anti-inflammatory activity and selectivity toward COX-2 of vanillyl methyl ketone was higher than eugenol. This was shown by the low binding energy affinity and the number of hydrogen bonds formed between the vanillyl methyl ketone and the active site of the enzyme. Keywords: eugenol, Wacker, vanillyl methyl ketone, antiinflammatory, in silico Pada penelitian ini dilakukan sintesis senyawa vanilil metil keton dari eugenol melalui oksidasi Wacker serta dilakukan uji aktivitas antiinflamasi terhadap enzim COX-1 dan COX-2 melalui analisis in silico. Proses oksidasi Wacker dikatalisis oleh PdCl2 dan CuCl2 menggunakan pelarut DMF dalam kondisi aerob pada suhu ruang selama 48 jam. Senyawa hasil sintesis dipisahkan menggunakan kolom kromatografi dan dikarakterisasi menggunakan spektroskopi NMR, IR dan MS. Hasil karakterisasi menunjukkan bahwa senyawa vanilil metil keton telah terbentuk dengan randemen sebanyak 45% dan juga dihasilkan senyawa vanillin (3%) sebagai produk samping. Aktivitas antiinflamasi senyawa vanilil metil keton dilakukan dengan docking molekuler terhadap enzim COX-1 dan COX-2 yang diperoleh dari PDB. Hasil analisis menunjukkan bahwa aktivitas antiinflamasi dan selektivitas terhadap COX-2 pada senyawa vanilil metil keton lebih tinggi dibandingkan eugenol. Hal ini ditunjukkan melalui rendahnya afinitas energi pengikatan dan banyaknya ikatan hidrogen yang terbentuk antara vanilil metil keton dengan sisi aktif enzim. Kata kunci : eugenol, Wacker, vanilil metil keton, antiinflamasi, in silico

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.

Investigation of indole functionalized pyrazoles and oxadiazoles as anti-inflammatory agents: synthesis, in-vivo, in-vitro and in-silico analysis

2021 ◽  
pp. 105068
Author(s):  
Devendra Kumar ◽  
Ravi Ranjan Kumar ◽  
Shelly Pathania ◽  
Pankaj Kumar Singh ◽  
Sourav Kalra ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Anti Inflammatory ◽  
Silico Analysis

scholarly journals IN SILICO DESIGN AND MOLECULAR DOCKING STUDIES OF SOME 1, 2-BENZISOXAZOLE DERIVATIVES FOR THEIR ANALGESIC AND ANTI-INFLAMMATORY ACTIVITY

2017 ◽  
Vol 9 (3) ◽  
pp. 133
Author(s):  
Sarath Sasi Kumar ◽  
Anjali T
Keyword(s):  
Molecular Docking ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Analgesic Activity ◽  
In Silico ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Nicotinic Acetylcholine ◽  
Cox 2 ◽  
Anti Inflammatory

Objective: In silico design and molecular docking of 1,2-benzisoxazole derivatives for their analgesic and anti-inflammatory activity using computational methods.Methods: In silico molecular properties of 1,2-benzisoxazole derivatives were predicted using various software’s such as Chemsketch, Molinspiration, PASS and Schrodinger to select compounds having optimum drug-likeness, molecular descriptors resembling those of standard drugs and not violating the ‘Lipinski rule of 5’. Molecular docking was performed on active site of nicotinic acetylcholine receptor (PDB: 2KSR) for analgesic activity and COX-2 (PDB: 6COX) for anti-inflammatory activity using Schrodinger under maestro molecular modelling environment.Results: From the results of molecular docking studies of 1,2-benzisoxazole derivatives, all the compounds showed good binding interactions with Nicotinic acetylcholine receptor and COX-2. Compounds 4a and 4c showed highest binding scores (-7.46 and-7.21 respectively) with nicotinic acetylcholine receptor and exhibited maximum analgesic activity. Compound 4a showed highest binding score (-7.8) with COX-2 and exhibited maximum anti-inflammatory activity.Conclusion: All the derivatives of 1,2-benzisoxazole showed good analgesic and anti-inflammatory activity as predicted using molecular docking on respective receptors.

scholarly journals ANTI-INFLAMMATORY ACTIVITY OF BACTERIA ASSOCIATED WITH MARINE SPONGE (HALICLONA AMBOINENSIS) VIA REDUCTING NO PRODUCTION AND INHIBITING CYCLOOXYGENASE-1, CYCLOOXYGENASE-2, AND SECRETORY PHOSPHOLIPASE A2 ACTIVITIES

2017 ◽  
Vol 10 (11) ◽  
pp. 95 ◽  
Author(s):  
Yosie Andriani ◽  
Leni Marlina ◽  
Habsah Mohamad ◽  
Hermansyah Amir ◽  
Siti Aisha M Radzi ◽  
...  
Keyword(s):  
Methanol Extract ◽  
Inflammatory Activity ◽  
No Production ◽  
Secretory Phospholipase A2 ◽  
Phytochemical Screening ◽  
Spla2 Activity ◽  
Cyclooxygenase 1 ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

  Objective: This study aimed to investigate the anti-inflammatory activity of methanol extract and fractions of bacteria associated with sponge (Haliclona amboinensis) and to evaluate their effect in reducing NO production and inhibiting cyclooxygenase-1 (COX-1), cyclooxgenase-2 (COX-2) and secretory phospholipase A2 (sPLA2) activity.Methods: All bacterial isolates were cultured and supernatants were collected for the extraction of secondary metabolites using diaion HP-20 to obtain methanol extracts. Evaluation of cytotoxicity property was carried out on macrophage cell lines (RAW264.7) by 3-(4,5-dimethylthiazol- 2-yl) 2,5-diphenyl tetrazoliumbromide assay. Anti-inflammatory screening was done by inducible nitric oxide assay on RAW264.7 cell lines with lipopolysaccharide (LPS) stimulation. Dianion HP-20 was used to remove salt content. A selected methanol extract was subjected to further fractionations by C-18 reverse phase and their anti-inflammatory potential was evaluated by COX-1 and COX-2, and sPLA2 enzymatic assay.Results: Seven methanol extracts showed no cytotoxic property against RAW 264.7 cell line (inhibitory concentration 50% > 30 μg/ml) and selected for anti-inflammatory screening assay. Result showed methanol extract HM 1.2 reduced NO production >80% and it has been selected for phytochemical screening, further fractionations and assay. Phytochemical screening showed alkaloids and terpenoids present in the HM 1.2. The HM 1.2 and its fractions (F1, F2, F1C1, F1C2, F1C3, and F1C4) were proven to inhibit COX-1, COX-2, and sPLA2 activity in the range of 60.516-116.886%, 20.554- 116.457%, and 70.2667-114.8148%, respectively.Conclusions: This study revealed that bacteria associated with H. amboinensis have produced anti-inflammatory activity via reducing NO production and inhibiting COX-1, COX-2, and sPLA2 activity. 

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 An Insight of Co-Encapsulation Nigella sativa and Cosmos caudatus Kunth Extracts as Anti-Inflammatory Agent Through In Silico Study

2021 ◽  
Vol 24 (5) ◽  
pp. 152-160
Author(s):  
Nadiyah Zuhroh ◽  
Zubaidah Ningsih ◽  
Anna Safitri
Keyword(s):  
Bioactive Compounds ◽  
In Silico ◽  
Nigella Sativa ◽  
In Vivo Studies ◽  
Drug Candidate ◽  
Active Compounds ◽  
Cosmos Caudatus ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

This study analyzes anti-inflammatory activity from extracts of Nigella sativa and Cosmos caudatus Kunth co-encapsulated through in silico molecular docking. The LC-MS results revealed that extracts of N. sativa mostly contained thymoquinone and alpha-hederin, whereas quercetin and kaempferol were the major compounds in C. caudatus K. Nevertheless, the bioactive compounds are usually susceptible to degradation by exposure to light, heat, oxygen, which may limit its biological activity. Therefore, encapsulation is one of the promising techniques to protect bioactive compounds. Ligands were encapsulated with chitosan and sodium tripolyphosphate as wall materials. Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) as the target enzymes were docked with a combination of these active compounds (non-encapsulated and encapsulated), using the HEX 8.0 program, and visualized using the Discovery studio visualizer software v16.1.0.15350. Interestingly, docking results of the combination of encapsulated ligands showed no interactions to COX-1 but interacted with COX-2. Therefore, co-encapsulation of extracts combinations has been suggested to act as anti-inflammatory agents targeted specifically to the COX-2 enzyme. The total energy of the encapsulated of combination of extract compounds to COX-2 were -1425.88 (mol/cal) for thymoquinone + quercetin; -1435.87 (mol/cal) for thymoquinone + kaempferol; 1175.97 (mol/cal) for quercetin + alpha hederin; -957.74 (mol/cal) for kaempferol + alpha hederin; and -283.3 (mol/cal) for diclofenac sodium, as a control NSAID drug. These suggest that encapsulated active compounds in N. sativa and C. caudatus K. have potency as a drug candidate for the selective NSAIDs category, which can be subjected to further in vitro and in vivo studies.

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