Anti-inflammatory and In Silico Docking Studies of Heterophragma adenophyllum Seem Stem Constituents

Glycosmis pentaphylla is traditionally used for treating many diseases in Bangladesh. Anti-inflammatory and analgesic effects of Glycosmis pentaphylla have been reported prominently but no bioactive element has been identified so far. In order to explore its analgesic and antiinflammatory compound(s), phytochemical analysis was conducted. Nine compounds were isolated from the methanol extract of leaves of Glycosmis pentaphylla whose structures were solved as arborinine (1), vanillic acid (2), 3-hydroxy-4-methoxybenzoic acid (3), benzoic acid (4), p-hydroxybenzoic acid (5), stigmasterol (6), β-amyrin (7), phytol (8) and 3α,16α-dihydroxyolean-12-ene (9) by spectroscopic studies, including high field 1H NMR analyses as well as co-TLC with authentic samples whenever possible. Among these, compounds 3 and 9 are the first report of their occurrence from G. pentaphylla. in silico docking studies of these metabolites with cyclooxygenase (COX)-2, an enzyme responsible for producing prostaglandins, were conducted. It was found that only arborinine and phytol can bind in the active site of COX-2, which might be considered as the major responsible moieties to cause analgesic and anti-inflammatory activities.

Download Full-text

Systematic Analysis of Compounds Present in Ocimum Tenuiflorum (Tulsi) Regarding its Anti-Inflammatory Properties Using In-Silico Techniques

Aresty Rutgers Undergraduate Research Journal ◽

10.14713/arestyrurj.v1i3.173 ◽

2021 ◽

Vol 1 (3) ◽

Author(s):

Jinay Patel ◽

Sonia Arora

Keyword(s):

In Silico ◽

Literature Search ◽

Data Bank ◽

Docking Studies ◽

Systematic Analysis ◽

Discovery Studio ◽

In Silico Docking ◽

Chemical Structures ◽

Ocimum Tenuiflorum ◽

Anti Inflammatory

The objective of this study was to gather data, create a database of the compounds present in Ocimum tenuiflorum (O. tenuiflorum), and gather related literature on the compounds found. A thor-ough literature search was performed to gather in-formation on compounds present in O. tenuiflorum, including chemical structures, relative abundance, presence in different plant parts, and availability from chemical supply vendors. The compounds’ chemical structures were refined using Discovery Studio Visualizer and Chimera software for future in-silico docking studies. The structures with cleaned structural geometry were obtained through D.S. Vis-ualizer for docking in the future. From the literature search of previously presented articles, it was found that methyl eugenol had the greatest percent com-position in O. tenuiflorum. After searching the Pro-tein Data Bank, COX-1, COX-2, and NF Kappa B were found to be the main protein targets of O. ten-uiflorum compounds in the arachidonic acid inflamematory pathway. Thus, the anti-inflammatory proper-ties of O. tenuiflorum have been analyzed in this ar-ticle for future in silico docking.

Download Full-text

Synthesis, Characterization, In-Silico Docking Study and In-Vitro AntiInflammatory Activities of Novel Chalcone Derivatives

10.47363/jbbr/2021(3)133 ◽

2021 ◽

Vol 3 (2) ◽

pp. 1-6

Author(s):

R Bharathi ◽

◽

N Santhi ◽

Keyword(s):

In Silico ◽

Aromatic Aldehydes ◽

Docking Study ◽

Docking Studies ◽

In Silico Docking ◽

Therapeutic Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Important Activity

A series of chalcones were synthesised by condensation of appropriate acetophenones with appropriate aromatic aldehydes, and their anti-inflammatory activities were investigated. In comparison to standard drugs, some have been found to have important activity. In silico docking, tests on chalcones were shown to be more selective to COX-2. Further anti-inflammatory results were supported by docking studies with COX-2. The results from the anti-inflammatory and docking indicate that the synthesised compounds 3b, 3g and 3h can be seen as therapeutic drugs.

Download Full-text

Synthesis, Anti-inflammatory Activity and Docking Studies of Some Newer 1,3-Thiazolidine-2,4-dione Derivatives as Dual Inhibitors of PDE4 and PDE7

Current Computer - Aided Drug Design ◽

10.2174/1573409914666181003151528 ◽

2019 ◽

Vol 15 (3) ◽

pp. 225-234 ◽

Cited By ~ 2

Author(s):

Himanshu Sharma ◽

Viney Lather ◽

Ajmer Singh Grewal ◽

Deepti Pandita

Keyword(s):

In Silico ◽

Cell Function ◽

Inflammatory Diseases ◽

Research Work ◽

Docking Studies ◽

Inflammatory Activity ◽

In Silico Docking ◽

Dual Inhibitors ◽

Anti Inflammatory

<P>Background: Phosphodiesterase 4 (PDE4) and phosphodiesterase 7 (PDE7), PDE superfamily members, increase inflammatory processes in immunomodulatory as well as pro-inflammatory cells via breakdown of cyclic adenosine monophosphate. Dual inhibitors of PDE4 and PDE7 are a novel class of drug candidates which can regulate pro-inflammatory as well as T-cell function and can be particularly advantageous in the treatment of a wide-ranging disorders associated with the immune system as well as inflammatory diseases with fewer unwanted adverse effects. Objective: The current research work was planned to design and synthesize some newer substituted 1,3- thiazolidine-2,4-dione derivatives as dual inhibitors of PDE4 and PDE7 followed by evaluation of their anti-inflammatory activity and in silico docking studies. Methods: A new series of substituted 1,3-thiazolidine-2,4-dione derivatives was synthesized followed by evaluation of their anti-inflammatory activity in animal models. In silico docking studies were performed for the evaluation of the binding pattern of synthesized derivatives in the binding site of both PDE4 and PDE7 proteins. Results: Amongst the newly synthesized derivatives, compounds 5 and 12 showed higher antiinflammatory activity in the animal model. The results of in vivo animal studies were found to be in concordance with the results of molecular docking studies. Conclusion: These newly synthesized derivatives can act as the lead molecules for the design of safe and therapeutically effective agents for various inflammatory diseases acting via inhibition of both PDE4 and PDE7.</P>

Download Full-text

Trigonella foenum-graecum Seeds Oil Attenuated Inflammation and Angiogenesis In Vivo through Down-Regulation of TNF-α

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666201005100132 ◽

2020 ◽

Vol 20 ◽

Author(s):

Muhammad Asif ◽

Hafiz Muhammad Yousaf ◽

Mohammed Saleem ◽

Malik Saadullah ◽

Tahir Ali Chohan ◽

...

Keyword(s):

In Silico ◽

Docking Studies ◽

Antioxidant Potential ◽

Cam Assay ◽

In Silico Docking ◽

Trigonella Foenum Graecum ◽

Tnf Α ◽

Anti Inflammatory

Introduction: Inflammation is a vital reaction of the natural immune system that protects against encroaching agents. However, uncontrolled inflammation can lead to complications. Trigonella foenum-graecum is traditionally used as an anti-inflammatory herb. Objectives: The current study was conducted to explore the antioxidant, anti-inflammatory, and antiangiogenic potentials of Trigonella foenum-graecum seeds oil. Methods: Oil was extracted from seeds of Trigonella foenum-graecum by cold press method and labelled as TgSO. Phytochemical (GCMS, Folin-Ciocalteu method) and metal analyses were conducted to evaluate the metalo-chemical profile of TgSO. In vitro antioxidant assays (2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid and ferric reducing antioxidant power) were performed to assess its antioxidant potential. In vitro antimicrobial property was evaluated using the agar disc diffusion method and the safety profile of TgSO was assessed following OECD 425 guidelines. In vivo anti-inflammatory activity of TgSO was assessed in carrageenan, serotonin, histamine, formalin, and cotton pellet-induced oedema models. Serum TNF-α, superoxide dismutase (SOD) and, catalases (CAT) levels were assessed by ELISA kit while the effects on angiogenesis were assessed by chick chorioallantoic membrane (CAM) assay. Histopathological studies using excised paws were conducted to observe the effect of TgSO treatment at the tissue level. In silico docking studies were conducted to screen binding potential of identified compounds towards TNF- α. Results: Extraction by cold press yielded 16% of TgSO. Phytochemical analysis of TgSO through GC-MS showed the presence of eugenol, dihydrocoumairn, and heptadecanoic acid, tri- and tetradecanoic acid and hexadecanoic acid respectively. Total phenolic contents of TgSO were found to be 37.1 ± 0.91 mg/g gallic acid equivalent in Folin-Ciocalteu method. Metal analysis indicated the presence of different metals in TgSO. Findings of antioxidant models showed moderate antioxidant potential of TgSO. Findings of antimicrobial assays showed that TgSO was active against S. aureus, S.epidermidis, C. albicans, and A. niger. In vivo toxicity study data showed that TgSO was safe up to the dose of 5000 mg/kg. Data of oedema models showed significant (p < 0.05) reduction in oedema development in TgSO treated animals in both acute and chronic models. Histopathological evaluations of paws showed minimal infiltration with inflammatory cells in TgSO-treated animals. Treatment also significantly (p < 0.05) down-regulated TNF-α in serum and while levels of SOD and CAT were upregulated. CAM assay findings revealed antiangiogenic activity of TgSO. Findings of in silico docking studies showed that identified phytoconstituents have potential to bind with culprit cytokine. Conclusion: Data of that current study conclude that TgSO has antioxidant, anti-inflammatory, and antiangiogenic effects that validate its traditional uses. Moreover, the synergistic actions of different phytoconstituents are proposed to be responsible for the observed effects.

Download Full-text

Facile Synthesis, Characterization and in Silico Docking Studies of Novel Thiazolidine-2,4-Dione-Based Mannich Base Bearing Furan/Thiophene Moiety as Promising Anti-Inflammatory Agents

Rwanda Journal of Engineering Science Technology and Environment ◽

10.4314/rjeste.v4i1.5 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Jean Baptiste Nkurunziza ◽

Pierre Dukuziyaturemye ◽

Edith Musabwa ◽

Balakrishna Kalluraya

Keyword(s):

In Silico ◽

Mannich Base ◽

Inflammatory Diseases ◽

Mannich Bases ◽

Docking Studies ◽

Secondary Amines ◽

Standard Drug ◽

In Silico Docking ◽

Thiophene Moiety ◽

Anti Inflammatory

Mannich bases are compounds bearing a β-amino carbonyl moiety. They are formed in the Mannich reaction that consists of an amino alkylation of an acidic proton placed next to a carbonyl functional group by formaldehyde and a primary or secondary amine. Mannich base products are known for their curative properties such as anti-inflammatory, antibacterial, anticancer, antifungal, anthelmintic, anticonvulsant, analgesic, anti-HIV, antipsychotic, antiviral, and antimalarial activities. Further, thiazolidinedione derivatives have shown to be efficacious in inflammatory diseases as wide-ranging as psoriasis, ulcerative colitis and non-alcoholic steatohepatitis. In light of the above observations, new series of thiazolidine-2,4-dione based Mannich base derivatives were synthesized via a simple and catalyst-free procedure involving the condensation of thiazolidine-2,4-dione, formaldehyde and secondary amines in DMF solvent. The structures of the newly synthesized compounds were confirmed by their IR, 1H-NMR, and Mass spectra. The synthesized compounds were tested for their in silico anti-inflammatory activity by Docking studies against COX-2 enzyme (PDB: 1CX2). Compounds 4a and 4b showed good in silico anti-inflammatory properties comparable to that of standard drug Diclofenac and may be considered as promising candidates for the development of new anti-inflammatory agents.

Download Full-text

Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

Current Bioactive Compounds ◽

10.2174/1573407213666170828165512 ◽

2019 ◽

Vol 15 (2) ◽

pp. 257-267 ◽

Cited By ~ 3

Author(s):

Paritosh Shukla ◽

Ashok Sharma ◽

Leena Fageria ◽

Rajdeep Chowdhury

Keyword(s):

Anticancer Activity ◽

Anticancer Agents ◽

In Silico ◽

Antimicrobial Agents ◽

Docking Studies ◽

Bioactive Molecules ◽

Microwave Assisted Synthesis ◽

Binding Affinities ◽

In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

Download Full-text

Hetero-Tricyclic Lead Scaffold as Novel PDE5A Inhibitor for Antihypertensive Activity: In Silico Docking Studies

Current Computer - Aided Drug Design ◽

10.2174/1573409915666190214161221 ◽

2019 ◽

Vol 15 (4) ◽

pp. 318-333

Author(s):

Dipak P. Mali ◽

Neela M. Bhatia

Keyword(s):

In Silico ◽

Docking Study ◽

Docking Studies ◽

Antihypertensive Activity ◽

In Silico Docking ◽

Π Stacking ◽

Π Stacking Interaction ◽

Nitrogen Heteroatom ◽

Inhibitory Potential ◽

Vlife Mds

Objective:To screen the phytochemicals for phosphodiesterase 5A (PDE5A) inhibitory potential and identify lead scaffolds of antihypertensive phytochemicals using in silico docking studies.Methods:In this perspective, reported 269 antihypertensive phytochemicals were selected. Sildenafil, a PDE5A inhibitor was used as the standard. In silico docking study was carried out to screen and identify the inhibiting potential of the selected phytochemicals against PDE5A enzyme using vLife MDS 4.4 software.Results:Based on docking score, π-stacking, H-bond and ionic interactions, 237 out of 269 molecules were selected which have shown one or more interactions. Protein residue Gln817A was involved in H-boding whereas Val782A, Phe820A and Leu804A were involved in π-stacking interaction with ligand. The selected 237 phytochemicals were structurally diverse, therefore 82 out of 237 molecules with one or more tricycles were filtered out for further analysis. Amongst tricyclic molecules, 14 molecules containing nitrogen heteroatom were selected for lead scaffold identification which finally resulted in three different basic chemical backbones like pyridoindole, tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline as lead scaffolds.Conclusion:In silico docking studies revealed that nitrogen-containing tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline tricyclic lead scaffolds have emerged as novel PDE5A inhibitors for antihypertensive activity. The identified lead scaffolds may provide antihypertensive lead molecules after its optimization.

Download Full-text