Synthesis, in vitro COX-1/COX-2 inhibition testing and molecular docking study of novel 1,4-benzoxazine derivatives

2019 ◽  
Vol 43 (26) ◽  
pp. 10305-10317 ◽  
Author(s):  
Mohammedumar M. Shaikh ◽  
Anuj P. Patel ◽  
Shivani P. Patel ◽  
Kishor H. Chikhalia
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Cox 2 ◽  
Cox 1

The present work deals with an efficient and straightforward synthesis, biological activity and molecular docking study of novel 1,4-benzoxazine derivatives.

Synthesis of new hexahydropyrimido[1,2-a]azepine derivatives bearing functionalized aryl and heterocyclic moieties as anti-inflammatory agents

2021 ◽  
Author(s):  
Hassanein H Hassanein ◽  
Doaa E Abdel Rahman ◽  
Marwa A Fouad ◽  
Rehab F Ahmed
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Study ◽  
In Vivo Studies ◽  
Molecular Docking Study ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

New hexahydropyrimido[1,2- a]azepine derivatives bearing functionalized aryl and heterocyclic moieties were synthesized as anti-inflammatory agents with better safety profiles. All synthesized compounds were assessed in vitro for their COX-1 and COX-2 inhibition activities. The most selective compounds, 2f, 5 and 6, were further evaluated for their in vivo anti-inflammatory activity and PGE2 inhibitory activity. To rationalize their selectivity, molecular docking within COX-1 and COX-2 binding sites was performed. Their physicochemical properties and drug-like nature profile were also calculated. The good activity and selectivity of compounds 2f, 5 and 6 were rationalized using a molecular docking study and supported by in vivo studies. These promising findings are encouraging for performing future investigations of these derivatives.

scholarly journals Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA of N-substituted 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones Derivatives

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2934 ◽  
Author(s):  
Edward Krzyżak ◽  
Dominika Szkatuła ◽  
Benita Wiatrak ◽  
Tomasz Gębarowski ◽  
Aleksandra Marciniak
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Serum Albumins ◽  
Molecular Docking Study ◽  
Binding Interaction ◽  
Ic50 Value ◽  
Cox 2 ◽  
Therapeutic Activities ◽  
Cox 1

Inhibition of cyclooxygenase is the way of therapeutic activities for anti-inflammatory pharmaceuticals. Serum albumins are the major soluble protein able to bind and transport a variety of exogenous and endogenous ligands, including hydrophobic pharmaceuticals. In this study, a novel N-substituted 1H-pyrrolo[3–c]pyridine-1,3(2H)-diones derivatives were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases and interactions with BSA. In vitro, COX-1 and COX-2 inhibition assays were performed. Interaction with BSA was studied by fluorescence spectroscopy and circular dichroism measurement. The molecular docking study was conducted to understand the binding interaction of compounds in the active site of cyclooxygenases and BSA. The result of the COX-1 and COX-2 inhibitory studies revealed that all the compounds potentially inhibited COX-1 and COX-2. The IC50 value was found similar to meloxicam. The intrinsic fluorescence of BSA was quenched by tested compounds due to the formation of A/E–BSA complex. The results of the experiment and molecular docking confirmed the main interaction forces between studied compounds and BSA were hydrogen bonding and van der Waals force.

scholarly journals A New N-Substituted 1H-Isoindole-1,3(2H)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking

2021 ◽  
Vol 22 (14) ◽  
pp. 7678
Author(s):  
Dominika Szkatuła ◽  
Edward Krzyżak ◽  
Paulina Stanowska ◽  
Magdalena Duda ◽  
Benita Wiatrak
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Biological Properties ◽  
Molecular Ions ◽  
Molecular Docking Study ◽  
Lipinski’S Rule ◽  
Cox 2 ◽  
Probable Path ◽  
Cox 1

Isoindoline-1,3-dione derivatives constitute an important group of medicinal substances. In this study, nine new 1H-isoindole-1,3(2H)-dione derivatives and five potential pharmacophores were obtained in good yield (47.24–92.91%). The structure of the new imides was confirmed by the methods of elemental and spectral analysis: FT–IR, H NMR, and MS. Based on the obtained results of ESI–MS the probable path of the molecules decay and the hypothetical structure of the resulting pseudo-molecular ions have been proposed. The physicochemical properties of the new phthalimides were determined on the basis of Lipiński’s rule. The biological properties were determined in terms of their cyclooxygenase (COX) inhibitory activity. Three compounds showed greater inhibition of COX-2, three compounds inhibited COX-1 more strongly than the reference compound meloxicam. From the obtained results, the affinity ratio COX-2/COX-1 was calculated. Two compounds had a value greater than that of meloxicam. All tested compounds showed oxidative or nitrosan stress (ROS and RNS) scavenging activity. The degree of chromatin relaxation outside the cell nucleus was lower than the control after incubation with all test compounds. The newly synthesized phthalimide derivatives showed no cytotoxic activity in the concentration range studied (10–90 µM). A molecular docking study was used to determined interactions inside the active site of cyclooxygenases.

COX-1/COX-2 inhibition activities and molecular docking study of newly designed and synthesized pyrrolo[3,4-c]pyrrole Mannich bases

2019 ◽  
Vol 27 (17) ◽  
pp. 3918-3928 ◽  
Author(s):  
Aleksandra Redzicka ◽  
Łukasz Szczukowski ◽  
Andrzej Kochel ◽  
Benita Wiatrak ◽  
Katarzyna Gębczak ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Mannich Bases ◽  
Molecular Docking Study ◽  
Cox 2 ◽  
Cox 1

scholarly journals Selective COX-2 Inhibitory Properties of Dihydrostilbenes from Liquorice Leaves–In Vitro Assays and Structure/Activity Relationship Study

2014 ◽  
Vol 9 (12) ◽  
pp. 1934578X1400901 ◽  
Author(s):  
Domenico Trombetta ◽  
Salvatore V. Giofrè ◽  
Antonio Tomaino ◽  
Roberto Raciti ◽  
Antonella Saija ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Docking Study ◽  
In Vitro Assays ◽  
Molecular Docking Study ◽  
Pge2 Release ◽  
Human Therapy ◽  
Glycyrrhiza Glabra L ◽  
Cox 2 ◽  
Cox 1

Three dihydrostilbenes belonging to the polyphenol pool characterized in the leaves of Sicilian liquorice ( Glycyrrhiza glabra L.) have been tested for their antioxidant and anti-inflammatory activity. The three dihydrostilbenes (PA-82, GA-23, DO-07) were in vitro tested to evaluate their capability to scavenge the stable radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), and to decrease thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) release in human whole blood samples. On the basis of the observed capability of these compounds to affect the cell COX-1/COX-2 pathway, a molecular docking study was carried out in order to understand in detail the ability of these compounds to bind to COX-1 and COX-2. The results show that the liquorice dihydrostilbenes are preferred ligands for COX-2 rather than for COX-1, providing a good rational for the observed selectivity in ex vivo experiments. Therefore, they appear to be good candidates for employment in human therapy against inflammation-related pathological conditions.

scholarly journals Molecular Docking Study of 3, 4- Dihydropyrimidone Derivatives as Novel Anti-inflammatory Agents

2021 ◽  
pp. 481-487
Author(s):  
Amit N. Panaskar ◽  
Ashish Jain ◽  
Pradeep Kumar Mohanty
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Docking Study ◽  
Protein Data Bank Code ◽  
Molecular Docking Study ◽  
Docking Score ◽  
Enzyme Active Site ◽  
Cox 2 ◽  
Anti Inflammatory

Aim: Currently, researchers have developed a lot of new active substances as anti-inflammatory agents. One of the target proteins for anti-inflammatory agents is the selective COX-2 active site. Selective COX-2 inhibition is the regulator of the inflammatory reaction cascade. In this research, 3, 4- Dihydropyrimidone derivatives were used to design the anti-inflammatory agent through a selective COX-2 inhibition. The potential activity of 3, 4- Dihydropyrimidone derivatives maybe increase due to the preparation of the Schiff base with aromatic aldehydes. Selective COX-2 inhibition was required to predict their anti-inflammatory activity so, the aim in the present study, molecular docking study of 3,4- dihydropyrimidone derivatives have performed using COX-2 enzyme active site. Methodology: The molecular docking of 3, 4-dihydropyrimidone derivatives were carried out using AutoDock vina Ver.1.1.2. Twenty 3,4-dihydropyrimidone derivatives were docked into the COX-2 active site with Protein data bank code 3LN1. The interactions were evaluated based on the docking score. Celecoxib was used as the reference standard for this study. Results: Twenty 3, 4- dihydropyrimidone derivatives showed the approximate docking score -8.4 to -10.1 kcal/mol. Fourteen 3,4-dihydropyrimidone derivatives have a greater docking score compared to celecoxib used as a standard compound. Derivative D-1 had higher binding energy than other 3,4-dihydropyrimidone derivatives because it has the smallest docking score. Conclusion: All new 3,4-dihydropyrimidone derivatives are feasible to synthesize and performed their in-vitro evaluation.

scholarly journals Biological Evaluation and Molecular Docking Studies of Benzalkonium Ibuprofenate

2020 ◽  
Author(s):  
Kodakkat Parambil Safna Hussan ◽  
Mohamed Shahin Thayyil ◽  
Thaikadan Shameera Ahamed ◽  
Karuvanthodi Muraleedharan
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Performance Enhancement ◽  
Docking Study ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Molecular Docking Study ◽  
Anti Inflammatory ◽  
Delivery Options

The third-generation ionic liquids (ILs), which are being used to produce double active pharmaceutical ingredients (d-APIs) with tunable biological activity along with novel performance, enhancement, and delivery options, have been revolutionizing the area of drug discovery since the past few decades. Herein we report the in vitro antibacterial and anti-inflammatory activity of benzalkonium ibuprofenate (BaIb) that are being used as in-house d-API, with a particular focus on its interaction with respective protein target through molecular docking study. The evaluation of the biological activity of BaIb with the antibacterial and anti-inflammatory target at the molecular level revealed that the synthesized BaIb could be designed as a potential double active drug since it retains the antibacterial and anti-inflammatory activity of its parent drugs, benzalkonium chloride (BaCl) and sodium ibuprofenate (NaIb), respectively.

Sign in / Sign up

Export Citation Format

Share Document