576 results match your criteria lipinski's rule

Novel 1,2,4-oxadiazole-chalcone/oxime hybrids as potential antibacterial DNA gyrase inhibitors: Design, synthesis, ADMET prediction and molecular docking study.

Bioorg Chem 2021 Apr 1;111:104885. Epub 2021 Apr 1.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, 82524 Sohag, Egypt. Electronic address:

New antibacterial drugs are urgently needed to tackle the rapid rise in multi-drug resistant bacteria. DNA gyrase is a validated target for the development of new antibacterial drugs. Thus, in the present investigation, a novel series of 1,2,4-oxadiazole-chalcone/oxime (6a-f) and (7a-f) were synthesized and characterized by IR, NMR (H and C) and elemental analyses. Read More

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Screening and molecular docking of selected phytochemicals against NS5B polymerase of hepatitis c virus.

Pak J Pharm Sci 2020 Sep;33(5(Supplementary)):2317-2322

Department of Biochemistry, Government College University, Faisalabad, Pakistan.

Hepatitis C virus (HCV) has major role in spreading of liver diseases worldwide. The HCV nonstructural NS5B is a polymerase (RdRp) that is present at the carboxylic-end of the polyprotein chain. It is essential and most important for the replication cycle. Read More

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September 2020

Discovery of novel Staphylococcus aureus penicillin binding protein 2a inhibitors by multistep virtual screening and biological evaluation.

Bioorg Med Chem Lett 2021 Mar 31:128001. Epub 2021 Mar 31.

Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, China; Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui, 230032, China. Electronic address:

Penicillin-binding protein 2a (PBP2a) is an essential protein involved in the resistance to β-lactam antibiotics acquired by methicillin-resistant Staphylococcus aureus (MRSA) and is a potential antibacterial target. In the current study, we employed a strategy that combined virtual screening with biological evaluation to discover novel inhibitors of PBP2a. In this investigation, a hybrid virtual screening method, consisting of drug-likeness evaluation (Lipinski's Rule of Five and ADMET) and rigid (LibDock) and semi-flexible (CDOCKER) docking-based virtual screenings, was used for retrieving novel PBP2a inhibitors from commercially available chemical databases. Read More

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Characterisation of twelve newly synthesised -(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests.

Arh Hig Rada Toksikol 2021 Mar 30;72(1):70-79. Epub 2021 Mar 30.

University of BelgradeFaculty of Technology and Metallurgy, Belgrade, Serbia.

In this study we screened twelve newly synthesised -(substituted phenyl)-2-chloroacetamides for antimicrobial potential relying on quantitative structure-activity relationship (QSAR) analysis based on the available cheminformatics prediction models (Molinspiration, SwissADME, PreADMET, and PkcSM) and verified it through standard antimicrobial testing against , , methicillin-resistant (MRSA), and . Our compounds met all the screening criteria of Lipinski's rule of five (Ro5) as well as Veber's and Egan's methods for predicting biological activity. In antimicrobial activity tests, all chloroacetamides were effective against Gram-positive and MRSA, less effective against the Gram-negative , and moderately effective against the yeast . Read More

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QSAR Modeling for Multi-Target Drug Discovery: Designing Simultaneous Inhibitors of Proteins in Diverse Pathogenic Parasites.

Front Chem 2021 10;9:634663. Epub 2021 Mar 10.

Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, João Pessoa, Brazil.

Parasitic diseases remain as unresolved health issues worldwide. While for some parasites the treatments involve drug combinations with serious side effects, for others, chemical therapies are inefficient due to the emergence of drug resistance. This urges the search for novel antiparasitic agents able to act through multiple mechanisms of action. Read More

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In silico studies on stilbenolignan analogues as SARS-CoV-2 Mpro inhibitors.

Adnan Cetin

Chem Phys Lett 2021 May 22;771:138563. Epub 2021 Mar 22.

Faculty of Health Sciences, University of Mus Alparslan, Mus 49250, Turkey.

COVID-19, a new strain of coronavirus family, was identified at the end of 2019 in China. The COVID-19 virus spread rapidly all over the world. Scientists strive to find virus-specific antivirals for the treatment of COVID-19. Read More

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The Discovery of Novel BCR-ABL Tyrosine Kinase Inhibitors Using a Pharmacophore Modeling and Virtual Screening Approach.

Front Cell Dev Biol 2021 4;9:649434. Epub 2021 Mar 4.

College of Pharmacy and Health Sciences, St. John's University, Queens, NY, United States.

Chronic myelogenous leukemia (CML) typically results from a reciprocal translocation between chromosomes 9 and 22 to produce the oncogene that when translated, yields the p210 BCR-ABL protein in more than 90% of all CML patients. This protein has constitutive tyrosine kinase activity that activates numerous downstream pathways that ultimately produces uncontrolled myeloid proliferation. Although the use of the BCR-ABL tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, dasatinib, bosutinib, and ponatinib have increased the overall survival of CML patients, their use is limited by drug resistance and severe adverse effects. Read More

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Synthesis of new α-Aryl-α-tetralones and α-Fluoro-α-aryl-α-tetralones, preliminary antiproliferative evaluation on drug resistant cell lines and in silico prediction of ADMETox properties.

Bioorg Chem 2021 Mar 4;110:104790. Epub 2021 Mar 4.

Laboratório de Química Bioorgânica, Instituto de Pesquisa de Produtos Naturais, Universidade Federal do Rio de Janeiro, Ilha do Fundão, CCS, Bloco H - Sala H27, 21941-902 Rio de Janeiro, RJ, Brazil. Electronic address:

α-aryl-α-tetralones and α-fluoro-α-aryl-α-tetralones derivatives were synthesized by palladium catalyzed α-arylation reaction of α-tetralones and α-fluoro-α-tetralones, with bromoarenes in moderate to good yields. These compounds were evaluated for their in vitro anti-proliferative effects against human breast cancer and leukemia cell lines with diverse profiles of drug resistance. The most promising compounds, 3b, 3c, 8a and 8c, were effective on both neoplastic models. Read More

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Ligand based 3D-QSAR model, pharmacophore, molecular docking and ADME to identify potential fibroblast growth factor receptor 1 inhibitors.

J Biomol Struct Dyn 2021 Mar 18:1-14. Epub 2021 Mar 18.

College of Life Sciences, Sichuan Agricultural University, Ya'an, China.

The FGF/FGFR system may affect tumor cells and stromal microenvironment through autocrine and paracrine stimulation, thereby significantly promoting oncogene transformation and tumor growth. Abnormal expression of FGFR1 in cells is considered to be the main cause of tumorigenesis and a potential target for the treatment of cancer. In this study, a combination of structure-based drug carriers and molecular docking-based virtual screening was used to screen new potential FGFR1 inhibitors. Read More

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Identification of new 3-phenyl-1H-indole-2-carbohydrazide derivatives and their structure-activity relationships as potent tubulin inhibitors and anticancer agents: A combined in silico, in vitro and synthetic study.

Bioorg Chem 2021 Mar 4;110:104795. Epub 2021 Mar 4.

Program in Chemical Sciences, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology (EHT), Commission on Higher Education (CHE), Ministry of Education, Bangkok 10400, Thailand. Electronic address:

Virtual screening of commercially available molecular entities by using CDRUG, structure-based virtual screening, and similarity identified eight new derivatives of 3-phenyl-1H-indole-2-carbohydrazide with anti-proliferative activities. The molecules were tested experimentally for inhibition of tubulin polymerisation, which revealed furan-3-ylmethylene-3-phenyl-1H-indole-2-carbohydrazide (27a) as the most potent candidate. Molecule 27a was able to induce G2/M phase arrest in A549 cell line, similar to other tubulin inhibitors. Read More

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Deep learning model for virtual screening of novel 3C-like protease enzyme inhibitors against SARS coronavirus diseases.

Comput Biol Med 2021 Mar 6;132:104317. Epub 2021 Mar 6.

School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India. Electronic address:

In the context of the recently emerging COVID-19 pandemic, we developed a deep learning model that can be used to predict the inhibitory activity of 3CLpro in severe acute respiratory syndrome coronavirus (SARS-CoV) for unknown compounds during the virtual screening process. This paper proposes a novel deep learning-based method to implement virtual screening with convolutional neural network (CNN) architecture. The descriptors represent chemical molecules, and these descriptors are input into the CNN framework to train a model and predict active compounds. Read More

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Potential of Pueraria tuberosa (Willd.) DC. to rescue cognitive decline associated with BACE1 protein of Alzheimer's disease on Drosophila model: An integrated molecular modeling and in vivo approach.

Int J Biol Macromol 2021 Mar 9;179:586-600. Epub 2021 Mar 9.

Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador. Electronic address:

The indispensable role of Beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) in Amyloid beta (Aβ) plaques generation and Aβ-mediated synaptic dysfunctions makes it a crucial target for therapeutic intervention in Alzheimer's disease (AD). In order to find out the potential inhibitors of BACE1, the present study focused on five phytochemicals from Pueraria tuberosa, namely, daidzin, genistin, mangiferin, puerarin, and tuberosin. A molecular docking study showed that all five phytochemicals presented the strongest BACE1 inhibition. Read More

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Structure-based virtual screening, molecular dynamics and binding affinity calculations of some potential phytocompounds against SARS-CoV-2.

J Biomol Struct Dyn 2021 Mar 8:1-18. Epub 2021 Mar 8.

Department of Pharmaceutical Sciences, Drug Discovery Research Laboratory, Assam University, Silchar, India.

COVID-19 caused by a positive-sense single stranded RNA virus named as severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) triggered the global pandemic. This virus has infected about 10.37 Crores and taken lives of 2. Read More

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Therapeutic Potentials of Fruit (Seed) Reflected into an Array of Pharmacological Assays and Prospective Receptors-Mediated Pathways.

Life (Basel) 2021 Feb 17;11(2). Epub 2021 Feb 17.

Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy.

(SF), a valuable Bangladeshi fruit, is considered an alternative therapeutic agent. Mainly, seeds are used as nutritional phytotherapy to ease physical and mental status by preventing chronic diseases. Here, we scrutinized the seed's fundamental importance in traditional medicine by following an integrated approach combining in vivo, in vitro, and in silico studies. Read More

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February 2021

Molecular docking and dynamics simulation to screen interactive potency and stability of fungicide tebuconazole with thyroid and sex hormone-binding globulin: Implications of endocrine and reproductive interruptions.

J Appl Toxicol 2021 Feb 25. Epub 2021 Feb 25.

Department of Nursing, University College Farasan Campus, Jazan University, Kingdom of Saudi Arabia.

Tebuconazole is a widely used fungicide in agriculture, and it may easily enter in the human food chain. In addition, tebuconzaol skin permeation coefficient (Log Kp) is -5.55 cm/s and it does not violate Lipinski's rule. Read More

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February 2021

Computational insight into the protective mechanism of Wendelbo. Alliaceae in a mouse model of Staphylococcosis: focus on dietary phytocannabinoid -caryophyllene.

In Silico Pharmacol 2021 7;9(1):17. Epub 2021 Feb 7.

Department of Biology, Faculty of Science, Razi University, Kermanshah, 67149-67346 Iran.

This study was aimed to investigate the prophylactic effects of hydro-alcoholic extract derived from bulbs of Wendelbo. (Alliaceae; AI) on mouse model of Staphylococcosis, and to decipher which phytochemicals of AI may involve in its anti-staphylococcal property. Male mice were allocated into four groups, i. Read More

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February 2021

Synthesis and in vitro study of antiproliferative benzyloxy dihydropyrimidinones.

Arch Pharm (Weinheim) 2021 Feb 15:e2000466. Epub 2021 Feb 15.

Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar, Gujarat, India.

In this study, we report on antiproliferative benzyloxy dihydropyrimidinones (DHPMs) produced by the Biginelli reaction of benzyloxy benzaldehyde, urea, and diverse 1,3-diones. The reaction was catalyzed by lanthanum triflate and completed within 1-1.5 h, with 74-97% yield. Read More

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February 2021

Exploring the active constituents of in intervention of novel coronavirus (COVID-19) based on molecular docking method.

Netw Model Anal Health Inform Bioinform 2021 6;10(1). Epub 2021 Feb 6.

Pharmaceutics Department, Gurunanak College of Pharmacy, Nari, Nagpur, Maharashtra 440026 India.

The severe acute respiratory syndrome COVID-19 declared a global pandemic by WHO has become the present wellbeing worry to the whole world. There is an emergent need to search for possible medications. We report in this study a molecular docking study of eighteen molecules with the main protease (M) responsible for the replication of SARS-CoV-2 virus. Read More

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February 2021

In silico Molecular Docking, DFT Analysis and ADMET Studies of Carbazole Alkaloid and Coumarins from Roots of : A Potent Inhibitor for Quorum Sensing.

Adv Appl Bioinform Chem 2021 5;14:13-24. Epub 2021 Feb 5.

Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, Adama, 1888, Ethiopia.

Introduction: In modern drug design, in silico methods are largely used to understand drug-receptor interactions and quantum chemical properties. In the present study, a computational de novo design approach was used to confirm mode of binding for antibacterial activity, elucidating quantum chemical properties and ADMET-drug-likeness of carbazole alkaloid () and three coumarins (-) isolated from roots of .

Methods: Docking studies were performed with DNA-Gyrase (6F86) and LasR binding domain (2UV0) employing a flexible ligand docking approach using AutoDock Vina. Read More

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February 2021

Antiproliferative Activity of Cissus quadrangularis L. Extract against Human Cervical Cancer Cells: In Vitro and In Silico Analysis.

Anticancer Agents Med Chem 2021 Feb 9. Epub 2021 Feb 9.

Department of Zoology, Aligarh Muslim University, Aligarh-202002. India.

Background: Ce rvical cancer is the second leading cause of cancer in women, which necessitates safe and potential therapeutic agents.

Objective: This study was designed to investigate the antiproliferative effect of ethanolic extract of Cissus quadrangularis L. (CQ) against human cervical adenocarcinoma HeLa cell line and in silico analysis of selected active agents against apoptosis executioner enzyme caspase-3. Read More

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February 2021

Molecular docking of alpha-enolase to elucidate the promising candidates against Streptococcus pneumoniae infection.

Daru 2021 Feb 3. Epub 2021 Feb 3.

Kulliyyah of Allied Health Sciences, International Islamic University Malaysia (IIUM), 25200, Kuantan, Pahang, Malaysia.

Purpose: To predict potential inhibitors of alpha-enolase to reduce plasminogen binding of Streptococcus pneumoniae (S. pneumoniae) that may lead as an orally active drug. S. Read More

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February 2021

Flavonol morin targets host ACE2, IMP-α, PARP-1 and viral proteins of SARS-CoV-2, SARS-CoV and MERS-CoV critical for infection and survival: a computational analysis.

J Biomol Struct Dyn 2021 Feb 1:1-32. Epub 2021 Feb 1.

Department of Orthopedics, Era's Lucknow Medical College and Hospital, Era University, Lucknow, UP, India.

A sudden outbreak of a novel coronavirus SARS-CoV-2 in 2019 has now emerged as a pandemic threatening to efface the existence of mankind. In absence of any valid and appropriate vaccines to combat this newly evolved agent, there is need of novel resource molecules for treatment and prophylaxis. To this effect, flavonol morin which is found in fruits, vegetables and various medicinal herbs has been evaluated for its antiviral potential in the present study. Read More

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February 2021

Structural Flexibility of Cyclosporine A Is Mediated by Amide - Isomerization and the Chameleonic Roles of Calcium.

J Phys Chem B 2021 02 1;125(5):1378-1391. Epub 2021 Feb 1.

Department of Chemistry, University of Tennessee, Knoxville, Tennessee 37996, United States.

Falling outside of Lipinski's rule of five, macrocyclic drugs have accessed unique binding sites of their target receptors unreachable by traditional small molecules. Cyclosporin(e) A (CycA), an extensively studied macrocyclic natural product, is an immunosuppressant with undesirable side effects such as electrolytic imbalances. In this work, a comprehensive view on the conformational landscape of CycA, its interactions with Ca, and host-guest interactions with cyclophilin A (CypA) is reported through exhaustive analyses that combine ion-mobility spectrometry-mass spectrometry (IMS-MS), nuclear magnetic resonance (NMR) spectroscopy, distance-geometry modeling, and NMR-driven molecular dynamics. Read More

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February 2021

Identification of potential inhibitors of SARS-CoV-2 main protease from compounds: A molecular docking study.

Chem Phys Lett 2020 Sep 30;754:137751. Epub 2020 Jun 30.

Department of Chemistry, Faculty of Sciences, University of Kinshasa, P.O Box 190, Kinshasa 11, Congo.

SARS-CoV-2 is the pathogen agent of the new corona virus disease that appeared at the end of 2019 in China. There is, currently, no effective treatment against COVID-19. We report in this study a molecular docking study of ten molecules with the main protease (3CLpro) responsible for the replication of coronaviruses. Read More

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September 2020

Structure based design, synthesis, and biological evaluation of imidazole derivatives targeting dihydropteroate synthase enzyme.

Bioorg Med Chem Lett 2021 Mar 26;36:127819. Epub 2021 Jan 26.

Department of Chemistry, School of Sciences, Gujarat University, Navarangpura, Gujarat, India. Electronic address:

In this study, we have designed and synthesized 2-((5-acetyl-1-(phenyl)-4-methyl-1H-imidazol-2-yl)thio)-N-(4-((benzyl)oxy)phenyl) acetamide derivatives. Antimicrobial activities of all the imidazole derivatives have been examined against Gram-positive and Gram-negative bacteria and results showed that the conjugates have appreciable antibacterial activity. Besides, several analogous were evaluated for their in vitro antiresistant bacterial strains such as Extended-spectrum beta-lactamases (ESBL), Vancomycin-resistant Enterococcus (VRE), and Methicillin-resistant Staphylococcus aureus (MRSA). Read More

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Properties of FDA-approved small molecule protein kinase inhibitors: A 2021 update.

Robert Roskoski

Pharmacol Res 2021 Mar 26;165:105463. Epub 2021 Jan 26.

Blue Ridge Institute for Medical Research, 3754 Brevard Road, Suite 116, Box 19 Horse Shoe, NC, 28742-8814, United States. Electronic address:

Owing to the dysregulation of protein kinase activity in many diseases including cancer, the protein kinase enzyme family has become one of the most important drug targets in the 21st century. There are 62 FDA-approved therapeutic agents that target about two dozen different protein kinases and eight of these were approved in 2020. All of the FDA-approved drugs are orally effective with the exception of netarsudil (a ROCK1/2 non-receptor protein-serine/threonine kinase antagonist given as an eye drop for the treatment of glaucoma) and temsirolimus (an indirect mTOR inhibitor given intravenously for the treatment of renal cell carcinoma). Read More

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Molecular structure, NBO analysis of the hydrogen-bonded interactions, spectroscopic (FT-IR, FT-Raman), drug likeness and molecular docking of the novel anti COVID-2 molecule (2E)-N-methyl-2-[(4-oxo-4H-chromen-3-yl)methylidene]-hydrazinecarbothioamide (Dimer) - quantum chemical approach.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Apr 29;251:119388. Epub 2020 Dec 29.

Department of Physics and Research Centre, Scott Christian College (Autonomous), Nagercoil 629003, Tamil Nadu, Affiliated to Manonmaniam Sundarnar University, Abishekapatti, Tirunelveli 627012, India. Electronic address:

Prospective antiviral molecule (2E)-N-methyl-2-[(4-oxo-4H-chromen-3-yl)methylidene]-hydrazinecarbothioamide has been probed using Fourier transform infrared (FTIR), FT-Raman and quantum chemical computations. The geometry equilibrium and natural bond orbital analysis have been carried out with density functional theory employing Becke, 3-parameter, Lee-Yang-Parr method with the 6-311G++(d,p) basis set. The vibrational assignments pertaining to different modes of vibrations have been augmented by normal coordinate analysis, force constant and potential energy distributions. Read More

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Identification of potential SARS-CoV-2 entry inhibitors by targeting the interface region between the spike RBD and human ACE2.

J Infect Public Health 2021 Feb 21;14(2):227-237. Epub 2020 Dec 21.

Department of Zoology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.

Coronavirus disease 2019 (COVID-19) is a fatal infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The virus infection is initiated upon recognition and binding of the spike (S) protein receptor-binding domain (RBD) to the host cell surface receptor, angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between S protein and ACE2 receptor is a novel approach to prevent the viral entry into the host cell. Read More

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February 2021

Molecular Docking and Molecular Dynamics Aided Virtual Search of OliveNet™ Directory for Secoiridoids to Combat SARS-CoV-2 Infection and Associated Hyperinflammatory Responses.

Front Mol Biosci 2020 7;7:627767. Epub 2021 Jan 7.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jazan University, Jazan, Saudi Arabia.

Molecular docking and molecular dynamics aided virtual search of OliveNet™ directory identified potential secoiridoids that combat SARS-CoV-2 entry, replication, and associated hyperinflammatory responses. OliveNet™ is an active directory of phytochemicals obtained from different parts of the olive tree, (Oleaceae). Olive oil, olive fruits containing phenolics, known for their health benefits, are indispensable in the Mediterranean and Arabian diets. Read More

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January 2021

In silico docking studies of α-amylase inhibitors from the anti-diabetic plant Benth. and an endophyte, .

3 Biotech 2021 Feb 11;11(2):51. Epub 2021 Jan 11.

Department of Studies in Botany, University of Mysore, Manasagangotri, Mysore, 570 006 Karnataka India.

In this investigation, potential inhibitors of α-amylase, one of the key regulatory enzymes in diabetes were characterized from the methanolic extract of Benth. (Lamiaceae), a traditional medicinal plant of the Western Ghats, southern India and the ethyl acetate extract of (JX965948), an endophytic actinomycete isolated from the stem fragments of , by Gas Chromatography and Mass Spectroscopy (GC-MS) technique followed by molecular docking studies. Forty-four compounds were detected in the solvent extracts of the host plant and the endophyte, respectively. Read More

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February 2021