scholarly journals Study of Molecular Docking of Alkaloid Derivative Compounds from Stem Karamunting (Rhodomyrtus tomentosa)Against α-Glucosidase Enzymes

2021 ◽  
Vol 9 (2) ◽  
pp. 129-136
Author(s):  
Budi Mulyati ◽  
Riong Seulina Panjaitan
Keyword(s):  
Molecular Docking ◽  
Medicinal Plant ◽  
Active Site ◽  
Active Sites ◽  
Biological Activities ◽  
Average Score ◽  
Ant System ◽  
Binding Score ◽  
Anti Inflammatory ◽  
Rhodomyrtus Tomentosa

Karamunting plant (Rhodomyrtus tomentosa) is a traditional medicinal plant. The leaves, roots, stems, and fruits of Karamunting have been identified, and their biological activities are antioxidants, antibacterial, antidiabetic, anti-inflammatory, and anticancer that contained alkaloids, tannins, and flavonoids. The types of alkaloids found in karamunting stems are homolycorine, ismine, lycorine, maritidine and tazetine. This study aims to determine the binding score of alkaloid-derived compounds with protein α-glucosidase and determine the protein's active site bound to the ligand. The method used in this research is Protein-Ligand ANT-System (PLANTS).  The results showed that the anchoring score of homolycorine was -60.83 kcal/mol, ismine -64.42 kcal/mol, lycorine -71.20 kcal/mol, maritidine -61.82 kcal/mol, and tazetine -65.02 kcal/mol. The active sites used for binding are Glu526, Gly555, and Pro556. The average score for anchoring alkaloid-derived compounds with protein α-glucosidase is 83.84%. This number indicates that karamunting stems can be used as antidiabetic.

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.

1'-methylspiro[indoline-3,4'-piperidine] Derivatives: Design, Synthesis, Molecular Docking and Anti-tumor Activity Studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Junjian Li ◽  
Lianbao Ye ◽  
Yuanyuan Wang ◽  
Ying Liu ◽  
Xiaobao Jin ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Active Sites ◽  
Biological Activities ◽  
Significant Inhibition ◽  
Alkaline Condition ◽  
Discovery Studio ◽  
Hela Cell Lines ◽  
Antiproliferative Activities

Background: Spirocyclic indoline compounds widely exist in numerous natural products with good biological activities and some drug molecules in many aspects. In recent years, it has attracted extensive attention as potent anti-tumor agents in the fields of pharmacology and chemistry. Objective: In this study, we focused on designing and synthesizing a set of novel 1'-H-spiro[indole-3,4'-piperidine] derivatives, which were evaluated by preliminary bioactivity experiment in vitro and molecular docking. Method: The key intermediate 1'-methylspiro[indoline-3,4'-piperidine] (B4) reacted with benzenesulfonyl chloride with different substituents under alkaline condition to obtain its sulfonyl derivatives (B5-B10). We evaluated their antiproliferative activities against A549, BEL-7402 and HeLa cells by MTT assay. We performed the CDOCKER module in Discovery Studio 2.5.5 software for molecular modeling of compound B5, and investigated the binding of compound B5 with the target proteins from PDB database. Results: The results indicated that compounds B4-B10 exhibited good antiproliferative activities against the above three types of cells, in which compound B5 with chloride atom as electron-withdrawing substituent on a phenyl ring showed the highest potency against BEL-7402 cells (IC50=30.03±0.43 μg/mL). By binging of the prominent bioactive compound B5 to CDK, c-Met, EGFR protein crystals, The binding energy of B5 with these three types receptors are -44.3583 kcal/mol, - 38.3292 kcal/mol, -33.3653 kcal/mol respectively. Conclusion: Six 1'-methylspiro[indoline-3,4'-piperidine] derivatives were synthesized and evaluated against BEL-7402, A- 549, HeLa cell lines. Compound B5 showed significant inhibition on BEL-7402 cell lines. Molecular docking revealed that B5 showed good affinity by the good fitting between B5 and these three targets with amino acid residues in active sites which encourage us to conduct further evaluation such as the kinase experiment.

Action of Thioglycosides of 1,2,4-Triazoles and Imidazoles on the Oxidative Stress and Glycosidases in Mice with Molecular Docking

2019 ◽  
Vol 16 (6) ◽  
pp. 696-710
Author(s):  
Mahmoud Balbaa ◽  
Doaa Awad ◽  
Ahmad Abd Elaal ◽  
Shimaa Mahsoub ◽  
Mayssaa Moharram ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Active Sites ◽  
Biological Activities ◽  
Imidazole Ring ◽  
Quantitative Structure Activity Relationship ◽  
Binding Interaction ◽  
Qsar Study

Background: ,2,3-Triazoles and imidazoles are important five-membered heterocyclic scaffolds due to their extensive biological activities. These products have been an area of growing interest to many researchers around the world because of their enormous pharmaceutical scope. Methods: The in vivo and in vitro enzyme inhibition of some thioglycosides encompassing 1,2,4- triazole N1, N2, and N3 and/or imidazole moieties N4, N5, and N6. The effect on the antioxidant enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) was investigated as well as their effect on α-glucosidase and β-glucuronidase. Molecular docking studies were carried out to investigate the mode of the binding interaction of the compounds with α- glucosidase and β -glucuronidase. In addition, quantitative structure-activity relationship (QSAR) investigation was applied to find out the correlation between toxicity and physicochemical properties. Results: The decrease of the antioxidant status was revealed by the in vivo effect of the tested compounds. Furthermore, the in vivo and in vitro inhibitory effects of the tested compounds were clearly pronounced on α-glucosidase, but not β-glucuronidase. The IC50 and Ki values revealed that the thioglycoside - based 1,2,4-triazole N3 possesses a high inhibitory action. In addition, the in vitro studies demonstrated that the whole tested 1,2,4-triazole are potent inhibitors with a Ki magnitude of 10-6 and exhibited a competitive type inhibition. On the other hand, the thioglycosides - based imidazole ring showed an antioxidant activity and exerted a slight in vivo stimulation of α-glucosidase and β- glucuronidase. Molecular docking proved that the compounds exhibited binding affinity with the active sites of α -glucosidase and β-glucuronidase (docking score ranged from -2.320 to -4.370 kcal/mol). Furthermore, QSAR study revealed that the HBD and RB were found to have an overall significant correlation with the toxicity. Conclusion: These data suggest that the inhibition of α-glucosidase is accompanied by an oxidative stress action.

Molecular Docking of the Terpenes in Gorgonian Corals to COX-2 and iNOS Enzymes as Anti-Inflammatory

2021 ◽  
Vol 19 ◽  
Author(s):  
Faruk Jayanto Kelutur ◽  
Nyi Mekar Saptarini ◽  
Resmi Mustarichie ◽  
Dikdik Kurnia
Keyword(s):  
Molecular Docking ◽  
Active Sites ◽  
Discovery Studio ◽  
Natural Medicine ◽  
Gorgonian Corals ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
The Right ◽  
Oxide Synthase ◽  
Free Energy Of Binding

Background: The inflammatory pathway is induced by cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzymes, so it requires the development of its inhibitors, such as nonsteroidal anti-inflammatory drugs (NSAIDs), but they have side effects. Therefore, the discovery and development of natural medicine as a lead compound are needed. The gorgonian corals have been reported to contain cyclic diterpenes with anti-inflammatory activities. The specific anti-inflammatory inhibitor potential has not been reported regarding these secondary metabolites, whether in COX-2 or iNOS. Thus, the in silico method is the right alternative. Objective: This study aimed to determine the potency of fifteen terpenes of the various gorgonian corals to COX-2 and iNOS enzymes as an anti-inflammatory Methods: Molecular docking was performed using ChemDraw Ultra 12.0, Chem3D Pro 12.0, Biovia Discovery Studio 2016 Client®, Autodock Tools 4.2, prediction pharmacokinetics (Pre-ADMET), and oral administration (Lipinski rule of five). Results: Potential terpenes based on ΔG (kcal/mol) and Ki (nM) to COX-2 were gyrosanol B (-10,32; 27,15), gyrosanol A (-10,20; 33,57), echinolabdane A (-9,81; 64,76). Only nine terpenes were specific to COX-2 active sites, while for iNOS were palmonine F (-7.76; 2070), briarenol C (-7.55; 2910), and all test compounds binding to the iNOS active sites. Pre-ADMET prediction obtained that HIA was very excellent (70–100%), Caco-2 had moderate permeability (4–70 nm sec-1), and PPB had strong binding (> 90%). Eight terpenes qualified for the Lipinski rule of five. Conclusion: NOS was a specific target for terpenes based on the free energy of binding (ΔG).

scholarly journals In silico and in vitro Demonstration of Homoharrintonine Antagonism of RBD-ACE2 Binding and its Anti-inflammatory and anti-thrombogenic Properties in a 3D human vascular lung model

2021 ◽  
Author(s):  
Shalini Saxena ◽  
Kranti Meher ◽  
Madhuri Rotella ◽  
Subhramanyam Vangala ◽  
Satish Chandran ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Sites ◽  
Cell Model ◽  
Antiviral Drugs ◽  
Lung Model ◽  
Host Cells ◽  
Spike Protein ◽  
Prevention And Treatment ◽  
Anti Inflammatory

Since 2019 the world has seen severe onslaught of SARS-CoV-2 viral pandemic. There is an urgent need for drugs that can be used to either prevent or treat the potentially fatal disease COVD-19. To this end, we screened FDA approved antiviral drugs which could be repurposed for COVID-19 through molecular docking approach in the various active sites of receptor binding domain (RBD). The RBD domain of SARS-CoV-2 spike protein is a promising drug target due to its pivotal role in viral-host attachment. Specifically, we focussed on identifying antiviral drugs which could a) block the entry of virus into host cells, b) demonstrate anti-inflammatory and/or anti-thrombogenic properties. Drugs which poses both properties could be useful for prevention and treatment of the disease. While we prioritized a few antiviral drugs based on molecular docking, corroboration with in vitro studies including a new 3D human vascular lung model strongly supported the potential of Homoharringtonine, a drug approved for chronic myeloid leukaemia to be repurposed for COVID-19. This natural product drug not only antagonized the biding of SARS-CoV-2 spike protein RBD binding to human angiotensin receptor 2 (ACE-2) protein but also demonstrated for the first time anti-thrombogenic and anti-leukocyte adhesive properties in a human cell model system. Overall, this work provides an important lead for development of rapid treatment of COVID-19 and also establishes a screening paradigm using molecular modelling and 3D human vascular lung model of disease to identify drugs with multiple desirable properties for prevention and treatment of COVID-19.

Synthesis of novel NSAIDs linked to triazolyl-oxadiazole heterocyclic compounds as more comprehensive antimicrobial agents: A computational molecular docking

2021 ◽  
Vol 17 ◽  
Author(s):  
Shaik Adamshafi ◽  
Venkatarao Veera ◽  
Mohan Rao SVM ◽  
Kishore Pilli VVN
Keyword(s):  
Molecular Docking ◽  
Antifungal Activity ◽  
Active Site ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Solubility Parameters ◽  
Diffusion Method ◽  
Binding Interaction ◽  
Protein Database ◽  
Chemical Structures

Introduction: Progress in the development of triazolyl-oxadiazoles is a bisphosphonate-700 inhibitor is still continuing with an outcome of the good scaffold as oxadiazole as well as triazoles individually for antibacterial activity. Hence, we proposed a suitable approach for the synthesis of dual heterocyclic analogues consisting of the therapeutically used non steroidal anti-inflammatory drugs in a combined form and evaluated for their antibacterial, antifungal activities, docking studies. Methods: The chemical structures were confirmed by various spectroscopic methods like IR, 1H NMR, 13C NMR, mass, and elemental analysis. The antibacterial, antifungal activity of these compounds was screened against Gram-positive, Gram-negative bacteria and fungal stains by agar well diffusion method. The crystal structure of S. aureus complexed with active site of bisphosphonate BPH-700 (2ZCS) was obtained from the Protein Database (PDB, http://www.rcsb.org). Molecular properties, drug likeness score, lipophilicity and solubility parameters by Molinspiration and Molsoft software. 7f (2-NO2, 5-Ome), 7g (3-Cl, 4-Cl), 7a (2-NO2) Results: Among the synthesised NSAID-triazolyl-oxadiazole containing 2-nitro-5-methoxy (7f), 3,4-dichloro (7g) derivatives were found to be high active antibacterial agents against S. aureus, E. coli with MICs 16, 19 μg/mL respectively. 2-nitro-5-methoxy (7f), 4-bromo (7h) and 2-nitro (7a) derivatives displayed superior antifungal activity against A. niger and MICs 56, 76, 130 μg/mL respectively. From molecular docking NSAID linked to 3,4-dichloro analogue (7g) revealed stronger binding interaction (ΔG =7.90 Kcal/Mol) with amino acids Asp49 (1.19 A˚), Arg45 (2.17 A˚), Lys17, Lys46 in the active site of S. aureus complexed with bisphosphonate Bph-700 (2ZCS). The compounds followed the Lipinski ‘Rule of five’ were synthesized for antimicrobial screening as oral bioavailable drugs/leads. Maximum drug likeness model score 0.49, 0.41 was found for compounds 7h, 7b. Conclusion: The present work, through simple synthetic approaches, led to the development of novel hybrids of triazole-oxadiazole pharmacophores that exhibited remarkable biological activities against different microorganisms. The compounds showed suitable drug like properties and are expected to present good bioavailability profile. Discussion: An efficient combination of molecular modeling and biological activity provided an insight into QSAR guide lines that could aid in further development of these derivatives.

scholarly journals Activity Prediction of Bioactive Compounds Contained in Etlingera elatior Against the SARS-CoV-2 Main Protease: An In Silico Approach

2020 ◽  
Vol 3 (4) ◽  
pp. 235-242
Author(s):  
Dwi Syah Fitra Ramadhan ◽  
Taufik Muhammad Fakih ◽  
Arfan Arfan
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
In Silico ◽  
Biological Activities ◽  
Activity Prediction ◽  
Ergosterol Peroxide ◽  
Main Protease ◽  
Promising Therapeutic Target ◽  
In Silico Methods ◽  
Etlingera Elatior

The COVID-19 pandemic has become a serious problem today, with its prevalence increasing every day. The SARS-CoV-2 main protease (MPro) is a promising therapeutic target to inhibit replicating and spreading the virus that causes COVID-19. The compounds contained in the Etlingera elatior plant has the potential. This study aimed to examine the compounds' activity in E. elatior against SARS-CoV-2 MPro using in silico methods. A total of seven compounds contained in E. elatior were obtained from the Knapsack database. The compounds were then docked into the SARS-CoV-2 MPro receptor's active site with the PDB ID 6LU7. Afterward, the biological activities were predicted by the PASS prediction webserver. The molecular docking results showed that ergosterol peroxide and sitostenone had the best binding energy with -10.40 kcal/mol and -9.17 kcal/mol, respectively. The in silico PASS prediction showed it has potential as antiviral therapy. It concluded ergosterol peroxide and sitostenone has the potential as SARS-CoV-2 MPro inhibitor candidate.

scholarly journals In silico study of anthocyanin and ternatin flavonoids for the treatment of inflammation-related diseases using molecular docking analysis

Food Research ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 780-785
Author(s):  
Y.T. Wijaya ◽  
A. Yulandi ◽  
A.W. Gunawan ◽  
Yanti
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Active Site ◽  
In Silico ◽  
Protein Crystal ◽  
Drug Candidate ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Inflammatory markers such as cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), and prostaglandin (PEG) are widely known as major targets in discovering natural anti-inflammatory drugs for the treatment of inflammationrelated diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin are mostly used at present, however, some NSAIDS have been reported to cause gastrointestinal side effect due to ligand-protein interaction. Molecular docking is a promising tool to study such modes of interaction. In this study, we evaluated the potential use of anthocyanin and ternatin flavonoids as natural anti-inflammatory agents for treatment of inflammatory-related diseases using in silico molecular docking assay. Automated docking study using Protein-Ligand ANT System (PLANTS) and AutoDock Vina was performed with various ligand molecules, including ibuprofen, anthocyanin, and ternatin against the protein crystal structures of COX-1, COX-2, iNOS, and MPO. The in silico data demonstrated that ibuprofen bound effectively to the active site of COX-1 and MPO with minimum binding energy, yet the compound required more energy to bind the active site of COX-2. Ternatin flavonoid was bound to COX-2 and iNOS with minimum binding energy. In terms of binding energy, anthocyanin flavonoid was found to be effective for inhibiting COX-1, COX-2, and iNOS. These results suggested that anthocyanin and ternatin flavonoids may potentially be developed as anti-inflammatory drug candidate for the treatment of inflammatory-related diseases.

3D Pharmacophore-based Ligand Alignment, Virtual Screening and Molecular Docking Protocols Towards the Discovery of 2-((1H-1,2,4-triazol-1- yl)methyl) Derivatives as Antifungal Inhibitors

2020 ◽  
Vol 16 (4) ◽  
pp. 498-513
Author(s):  
Mohamed E. I. Badawy ◽  
Saad R. El-Zemity
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Phenyl Ring ◽  
Active Sites ◽  
Antifungal Agents ◽  
Biological Activities ◽  
Pharmacophore Modeling ◽  
Microbial Pathogens ◽  
In Silico Studies ◽  
Methyl Derivatives

Background: 1,2,4-Triazoles are important five-membered heterocyclic scaffolds due to their extensive biological activities. These products have been an area of growing interest to many researchers around the world as of their diverse biological activities including antifungal and antibacterial activity against broad spectrum of microbial pathogens. Methods: A series of 2-((1H-1,2,4-triazol-1-yl)methyl) derivatives was designed, synthesized and evaluated as antifungal agents against five plant pathogenic fungi (Alternaria tennis, Botryodiplodia theobromae, Fusarium moniliforme, Fusarium oxysporum and Helminthosporium turcicum) to meet the urgent need of new antifungal agents with improved activity and broader spectrum. In silico studies including pharmacophore modeling, virtual screening, drug-likeness analysis and ADMET prediction were examined. In addition, the elucidation of the activity is based on the molecular docking to the active site of the Sterol 14α-Demethylase Cytochrome P450 (CYP51) was investigated. Results: The results of antifungal activity indicated that the compounds containing tert or sec-butyl as hydrophobic substituents on a phenyl ring significantly increased the activity (compounds 4, 5 and 6) with EC50 in the range of 8-84 mg/L of all tested fungi. The pharmacophore modeling produced an accurate projecting model (Hypo 1) from these derivatives. The superlative Hypo1 consists of three features counting two hydrogen bond acceptors (HBA) and one hydrophobic (HYD). The docking results showed approximately a similar binding degree at the active sites of the fungal enzyme (CYP51) as a standard fungicide penconazole. Conclusion: According to data obtained, some derivatives, especially those with tert or sec-butyl substituents on the phenyl ring, were more potent against phytopathogenic fungi. These compounds (e.g., 4, 5, and 6) should develop into new potential fungicides as a desirable activity.

scholarly journals Evaluation of Anti-HIV-1 Integrase and Anti-Inflammatory Activities of Compounds from Betula alnoides Buch-Ham

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Prapaporn Chaniad ◽  
Teeratad Sudsai ◽  
Abdi Wira Septama ◽  
Arnon Chukaew ◽  
Supinya Tewtrakul
Keyword(s):  
Active Sites ◽  
Biological Activities ◽  
Ethanol Extract ◽  
Strand Transfer ◽  
Computational Docking ◽  
Pentacyclic Triterpenoid ◽  
Anti Inflammatory ◽  
Betula Alnoides ◽  
Anti Hiv ◽  
Hiv 1

Betula alnoides is a medicinal plant in Thai traditional longevity preparations. The crude extracts of this plant possess various biological activities. However, the isolated compounds from this plant have no reports of anti-HIV-1 integrase (IN) activity. Therefore, the present study aims to investigate the anti-HIV-1 integrase and anti-inflammatory effects of isolated compounds from this plant and predict the interaction of compounds with integrase active sites. From the bioassay-guided fractionation of the ethanol extract of B. alnoides stems using chromatographic techniques, five pentacyclic triterpenoid compounds were obtained. They are betulinic acid (1), betulin (2), lupeol (3), oleanolic acid (4), and ursolic acid (5). Compound 2 exhibited the most potent inhibitory activity against HIV-1 IN, with an IC50 value of 17.7 μM. Potential interactions of compounds with IN active sites were investigated using computational docking. The results indicated that active compounds interacted with Asp64, a residue participating in 3′-processing, and Thr66, His67, and Lys159, residues participating in strand-transfer reactions of the integration process. Regarding anti-inflammatory activity, all compounds exerted significant inhibitory effects on LPS-induced nitric oxide production (IC50 < 68.7 μM). Thus, this research provides additional scientific support for the use of B. alnoides in traditional medicine for the treatment of HIV patients.

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