scholarly journals Biological Evaluation and Molecular Docking Studies of Dimethylpyridine Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1093 ◽  
Author(s):  
Piotr Świątek ◽  
Katarzyna Gębczak ◽  
Tomasz Gębarowski ◽  
Rafal Urniaz
Keyword(s):  
Molecular Docking ◽  
Biological Evaluation ◽  
In Vivo Studies ◽  
Cyclooxygenase Inhibitors ◽  
Anticancer Activities ◽  
Molecular Docking Study ◽  
Binding Interaction ◽  
Cox 2 ◽  
Cox 1

Cyclooxygenase inhibitors as anti-inflammatory agents can be used in chemoprevention. Many in vitro and in vivo studies on human and animal models have explained the mechanisms of the chemopreventive effect of COX inhibitors such as: induction of apoptosis, inhibition of neoplasia, angiogenesis suppression, induction of cell cycle inhibition and inhibition of the expression of peroxisome proliferator-activated receptors. Here, biological evaluation of twelve different Schiff base derivatives of N-(2-hydrazine-2-oxoethyl)-4,6-dimethyl-2-sulfanylpyridine- 3-carboxamide are presented. Their in vitro anti-COX-1/COX-2, antioxidant and anticancer activities were studied. The molecular docking study was performed in order to understand the binding interaction of compounds in the active site of cyclooxygenases. Compounds PS18 and PS33 showed a significant inhibitory activity on COX-1 at lower concentrations compared to meloxicam and piroxicam. The IC50 of COX-1 of these compounds was 57.3 µM for PS18 and 51.8 µM for PS33. Out of the tested compounds, the highest therapeutic index was demonstrated by PS18, PS19, PS33, PS40 and PS41. Lower molar concentrations of these compounds inhibit the growth of cancer cells while not inhibiting the healthy cells. Compounds PS18, PS19 and PS33 simultaneously demonstrated a statistically-significant inhibition of COX-1 or COX-2. This opens up the possibility of applying these compounds in the chemoprevention of cancer.

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.

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.

scholarly journals In Vitro and In Silico Evaluation of New 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone as Promising Cyclooxygenase Inhibitors

2021 ◽  
Vol 22 (17) ◽  
pp. 9130
Author(s):  
Krzysztof Peregrym ◽  
Łukasz Szczukowski ◽  
Benita Wiatrak ◽  
Katarzyna Potyrak ◽  
Żaneta Czyżnikowska ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Binding Mode ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Cyclooxygenase Inhibitors ◽  
Molecular Docking Studies ◽  
Cox 2 ◽  
Derivatives Of

Since long-term use of classic NSAIDs can cause severe side effects related mainly to the gastroduodenal tract, discovery of novel cyclooxygenase inhibitors with a safe gastric profile still remains a crucial challenge. Based on the most recent literature data and previous own studies, we decided to modify the structure of already reported 1,3,4-oxadiazole based derivatives of pyrrolo[3,4-d]pyridazinone in order to obtain effective COX inhibitors. Herein we present the synthesis, biological evaluation and molecular docking studies of 12 novel compounds with disubstituted arylpiperazine pharmacophore linked in a different way with 1,3,4-oxadiazole ring. None of the obtained molecules show cytotoxicity on NHDF and THP-1 cell lines and, therefore, all were qualified for further investigation. In vitro cyclooxygenase inhibition assay revealed almost equal activity of new derivatives towards both COX-1 and COX‑2 isoenzymes. Moreover, all compounds inhibit COX-2 isoform better than Meloxicam which was used as reference. Anti-inflammatory activity was confirmed in biological assays according to which title molecules are able to reduce induced inflammation within cells. Molecular docking studies were performed to describe the binding mode of new structures to cyclooxygenase. Investigated derivatives take place in the active site of COX, very similar to Meloxicam. For some compounds, promising druglikeness was calculated using in silico predictions.

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.

scholarly journals Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives

2018 ◽  
Vol 26 (20) ◽  
pp. 5388-5396 ◽  
Author(s):  
Ana Daura Travassos de Oliveira Moraes ◽  
Mirelly Dianne Santos de Miranda ◽  
Íris Trindade Tenório Jacob ◽  
Cézar Augusto da Cruz Amorim ◽  
Ricardo Olímpio de Moura ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Biological Evaluation ◽  
Molecular Docking Study ◽  
Cox 1

scholarly journals Biological Evaluation and Molecular Docking Studies of Novel 1,3,4-Oxadiazole Derivatives of 4,6-Dimethyl-2-sulfanylpyridine-3-carboxamide

2022 ◽  
Vol 23 (1) ◽  
pp. 549
Author(s):  
Piotr Świątek ◽  
Teresa Glomb ◽  
Agnieszka Dobosz ◽  
Tomasz Gębarowski ◽  
Kamil Wojtkowiak ◽  
...  
Keyword(s):  
Schiff Base ◽  
Molecular Docking ◽  
Density Functional ◽  
Control Cell ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Selectivity Ratio ◽  
Anticancer Activities ◽  
Cox 2 ◽  
Cox 1

To date, chronic inflammation is involved in most main human pathologies such as cancer, and autoimmune, cardiovascular or neurodegenerative disorders. Studies suggest that different prostanoids, especially prostaglandin E2, and their own synthase (cyclooxygenase enzyme-COX) can promote tumor growth by activating signaling pathways which control cell proliferation, migration, apoptosis, and angiogenesis. Non-steroidal anti-inflammatory drugs (NSAIDs) are used, alongside corticosteroids, to treat inflammatory symptoms particularly in all chronic diseases. However, their toxicity from COX inhibition and the suppression of physiologically important prostaglandins limits their use. Therefore, in continuation of our efforts in the development of potent, safe, non-toxic chemopreventive compounds, we report herein the design, synthesis, biological evaluation of new series of Schiff base-type hybrid compounds containing differently substituted N-acyl hydrazone moieties, 1,3,4-oxadiazole ring, and 4,6-dimethylpyridine core. The anti-COX-1/COX-2, antioxidant and anticancer activities were studied. Schiff base 13, containing 2-bromobenzylidene residue inhibited the activity of both isoenzymes, COX-1 and COX-2 at a lower concentration than standard drugs, and its COX-2/COX-1 selectivity ratio was similar to meloxicam. Furthermore, the results of cytotoxicity assay indicated that all of the tested compounds exhibited potent anti-cancer activity against A549, MCF-7, LoVo, and LoVo/Dx cell lines, compared with piroxicam and meloxicam. Moreover, our experimental study was supported by density functional theory (DFT) and molecular docking to describe the binding mode of new structures to cyclooxygenase.

Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

2020 ◽  
Vol 16 (7) ◽  
pp. 892-902 ◽  
Author(s):  
Aida Iraji ◽  
Mahsima Khoshneviszadeh ◽  
Pegah Bakhshizadeh ◽  
Najmeh Edraki ◽  
Mehdi Khoshneviszadeh
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Docking Study ◽  
Biological Evaluation ◽  
Primary Response ◽  
Ratio Method ◽  
Molecular Docking Study ◽  
Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

scholarly journals STRUCTURE-BASED MULTITARGETED MOLECULAR DOCKING ANALYSIS OF PYRAZOLE-CONDENSED HETEROCYCLICS AGAINST LUNG CANCER

2021 ◽  
pp. 157-169
Author(s):  
JAINEY P. JAMES ◽  
AISWARYA T. C. ◽  
SNEH PRIYA ◽  
DIVYA JYOTHI ◽  
SHESHAGIRI R. DIXIT
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Binding Mode ◽  
Pharmacophore Modeling ◽  
In Vivo Studies ◽  
Spectral Studies ◽  
Pyrazole Derivatives ◽  
Anticancer Activities

Objective: The significant drawbacks of chemotherapy are that it destroys healthy cells, resulting in adverse effects. Hence, there is a need to adopt new techniques to develop cancer-specific chemicals that target the molecular pathways in a non-toxic fashion. This study aims to screen pyrazole-condensed heterocyclics for their anticancer activities and analyse their enzyme inhibitory potentials EGFR, ALK, VEGFR and TNKS receptors. Methods: The structures of the compounds were confirmed by IR, NMR and Mass spectral studies. The in silico techniques applied in this study were molecular docking and pharmacophore modeling to analyse the protein-ligand interactions, as they have a significant role in drug discovery. Drug-likeness properties were assessed by the Lipinski rule of five and ADMET properties. Anticancer activity was performed by in vitro MTT assay on lung cancer cell lines. Results: The results confirm that all the synthesised pyrazole derivatives interacted well with the selected targets showing docking scores above-5 kcal/mol. Pyrazole 2e interacted well with all the four lung cancer targets with its stable binding mode and was found to be potent as per the in vitro reports, followed by compounds 3d and 2d. Pharmacophore modeling exposed the responsible features responsible for the anticancer action. ADMET properties reported that all the compounds were found to have properties within the standard limit. The activity spectra of the pyrazoles predicted that pyrazolopyridines (2a-2e) are more effective against specific receptors such as EGFR, ALK and Tankyrase. Conclusion: Thus, this study suggests that the synthesised pyrazole derivatives can be further investigated to validate their enzyme inhibitory potentials by in vivo studies.

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