scholarly journals PENENTUAN SENYAWA POTENSIAL DARI BUAH SEMANGKA (Citrullus Lanatus) SEBAGAI KANDIDAT OBAT DISLIPIDEMIA

2019 ◽  
Vol 10 (1) ◽  
pp. 42
Author(s):  
Muhammad Fauzi ◽  
Effan Cahyati Junaedi ◽  
Agus Rusdin
Keyword(s):  
Molecular Docking ◽  
Citrullus Lanatus ◽  
Lipinski’S Rule ◽  
Protein Target ◽  
Lipinski’S Rule Of Five

Dislipedemia merupakan penyakit yang disebabkan oleh abnormalitas pada metabolisme lipid. Sampai saat ini simvastatin masih menjadi lini pertama dalam pengobatan dislipidemia. Namun selain mengggunakan obat sintetis, bahan alam juga dapat dimanfaatkan dalam mengatasi kolesterol tinggi sebagai alternatif menurunkan kadar kolesterol. Salah satunya adalah buah semangka (Citrullus lanatus) yang mengandung senyawa arginine, betain, sitrulin, kukurbitasin, likopen dan pekin. Penelitian ini dilakukan dengan menggunakan metode penambatan molekuler (molecular docking) yang digunakan untuk menyeleksi senyawa berdasarkan interaksinya dengan protein target dan prediksi biovaibilitasnya.. Tujuan penelitian ini adalah mencari potensi senyawa dari buah semangka untuk dijadikan kandidat obat dislipidemia. Molecular docking terhadap simvastatin sebagai obat pembanding memberikan energi bebas sebesar -9.05 kkal/mol dengan asam amino yang terikat adalah LYS692, ALA751, LYS735, ARG590, SER684, LYS691, ASN755. Serin (SER684) merupakan asam amino kunci dan sering memainkan peran penting dalam katalisator enzim. Hasil pengujian terhadap 6 senyawa yang terkandung didalam buah semangka, terdapat dua senyawa potensial yaitu sitrulin dan pektin. Senyawa sitrulin memberikan energi bebas -5.67 kkal/mol dengan asam amino yang terikat adalah GLU559, ARG590, LYS735, SER684, LYS692, ASP690. Senyawa pektin memberikan energi bebas -7.27 kkal/mol dengan asam amino yang terikat adalah ARG590, SER684, LYS692, ASP690, LYS691. Artinya senyawa tersebut mampu menghambat biosintesis kolesterol. Penentuan prediksi sifat biovaibilitas menunjukkan semua senyawa memenuhi parameter Lipinski’s rule of five sehingga kedua senyawa tersebut berpotensi sebagai kandidat obat dislipidemia. Kata kunci: Buah Semangka, Dislipidemia, Molecular Docking

scholarly journals Molecular Docking Studies of Flavonoids from Andrographis paniculata as Potential Acetylcholinesterase, Butyrylcholinesterase and Monoamine Oxidase Inhibitors Towards the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 11 (3) ◽  
pp. 9871-9879
Keyword(s):  
Molecular Docking ◽  
Monoamine Oxidase ◽  
Neurodegenerative Diseases ◽  
Docking Studies ◽  
Monoamine Oxidase Inhibitors ◽  
Andrographis Paniculata ◽  
Lipinski’S Rule ◽  
Bioinformatic Tools ◽  
Pubchem Database ◽  
Lipinski’S Rule Of Five

Neurodegenerative diseases have been characterized by loss of neuron structures as well as their functions. This study was designed to assess molecular docking of flavonoids from Andrographis paniculata as potential acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase inhibitors in the treatment of neurodegenerative diseases. Eight identified possible inhibitors of acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase from Andrographis paniculata were retrieved from the PubChem database. The molecular docking, ADMET, and Lipinski’s rule of five were examined using different bioinformatic tools. It was shown that only rutin has the highest binding affinity (-12.6 kcal/mol) than the standard used. ADMET results demonstrated that all the eight compounds are druggable candidates except rutin. Also, only tangeritin has a blood-brain barrier (BBB) permeation potential. Hence, it can be deduced that all flavonoid compounds from Andrographis paniculata are orally druggable, which can make them useful in the treatment of neurodegenerative diseases better than donepezil.

scholarly journals In-silico pharmacophore and Molecular Docking based drug discovery against Marburg Virus Viral Protein VP35; A potent of MAVD.

2021 ◽  
Author(s):  
Sameer Quazi ◽  
Shreelaxmi Gavas ◽  
Javed Ahmad Malik ◽  
Komal Singh Suman ◽  
Zeshan Haider
Keyword(s):  
Molecular Docking ◽  
Viral Protein ◽  
Virus Disease ◽  
Antiviral Drug ◽  
Computational Approach ◽  
Marburg Virus ◽  
Online Tool ◽  
Lipinski’S Rule ◽  
Zinc Database ◽  
Lipinski’S Rule Of Five

Marburg virus is a member of filoviridae and spreads severe Marburg hemorrhagic illness in humans and animals. Nowadays, there is no vaccine available that can completely stop the replication of Marburg replication. Therefore, this study is designed to repurpose the effective therapeutic antiviral drug by using a computational approach against exploring the mechanism of Marburg virus Viral protein 35. We have retrieved about 40570 drug-like small compounds from the ZINC database using the "ZINC Pharmer" online tool. Molecular docking of the ligands from the ready-to-dock database has been carried out using MOE. The five drugs have been identified to bind with VP35 possibly. A study was also performed to evaluate the drug-like characteristics of the substances for absorption, distribution, metabolism, and excretion (ADME). The findings clearly showed that ligands are interacting with the MARV VP35 protein. Interestingly, Lipinski's rule of five was observed by all ligands. These findings provide the foundation for reconstituting and utilizing molecules as a possible therapy for Marburg Virus Disease (MVD).

scholarly journals Novel Coronavirus (SARS-CoV-2) Main Protease: Molecular docking of Puerarin as a Potential inhibitor

2020 ◽  
Author(s):  
Oluwafemi Adeleke Ojo ◽  
Adebola Busola Ojo ◽  
Odunayo Anthonia Taiwo ◽  
Olarewaju M Oluba
Keyword(s):  
Molecular Docking ◽  
Rna Virus ◽  
Drug Candidate ◽  
Lipinski’S Rule ◽  
Global Pandemic ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Novel Coronavirus ◽  
Research World ◽  
High Binding Affinity

Abstract SARS-CoV-2 a single stranded RNA virus which triggered the global pandemic Coronavirus Disease- 2019 (COVID-2019). It has infected about 2,844,712 patients and brought forth mortality rate to about 201,315 among 216 countries as cited by WHO. Drugs including Chloroquine and Hydroxychloroquine derivatives are being administered in most urgent cases; although, with probable side effects to people with metabolic disorders. Thus, unavailability of authorized drugs and treatment for this pandemic demands the research world to discover natural compounds with potency to cure it. This paper assesses the isoflavonoid puerarin from Pueraria lobata as a possible inhibitor of the main protease of SARS-COV-2 (Mpro) via in silico approach, for example molecular docking, Lipinski’s rule of five and toxicity prediction (ADME). Puerarin revealed high binding affinity with the target site of SARS-CoV-2 main protease. This compound slightly meets the criteria of Lipinski’s rule and does not possess properties that could cause adverse effects in humans thus, making puerarin a potential drug candidate to investigate for its usage against COVID-19.

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

2021 ◽  
Vol 7 ◽  
Author(s):  
Neelaveni Thangavel ◽  
Mohammad Al Bratty ◽  
Hassan Ahmad Al Hazmi ◽  
Asim Najmi ◽  
Reem Othman Ali Alaqi
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Oral Absorption ◽  
Olive Tree ◽  
Viral Disease ◽  
S Protein ◽  
Lipinski’S Rule ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
The Moment

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, Olea europaea (Oleaceae). Olive oil, olive fruits containing phenolics, known for their health benefits, are indispensable in the Mediterranean and Arabian diets. Secoiridoids is the largest group of olive phenols and is exclusive to the olive fruits. Functional food like olive fruits could help prevent and alleviate viral disease at an affordable cost. A systematized virtual search of 932 conformers of 78 secoiridoids utilizing Autodock Vina, followed by precision docking using Idock and Smina indicated that Nüzhenide oleoside (NZO), Oleuropein dimer (OED), and Dihydro oleuropein (DHO) blocked the SARS-CoV-2 spike (S) protein-ACE-2 interface; Demethyloleuropein (DMO), Neo-nüzhenide (NNZ), and Nüzhenide (NZE) blocked the SARS-CoV-2 main protease (Mpro). Molecular dynamics (MD) simulation of the NZO-S-protein-ACE-2 complex by Desmond revealed stability during 50 ns. RMSD of the NZO-S-protein-ACE-2 complex converged at 2.1 Å after 20 ns. During MD, the interaction fractions confirmed multiple interactions of NZO with Lys417, a crucial residue for inhibition of S protein. MD of DMO-Mpro complex proved its stability as the RMSD converged at 1.6 Å. Analysis of interactions during MD confirmed the interaction of Cys145 of Mpro with DMO and, thus, its inhibition. The docking predicted IC50 of NZO and DMO was 11.58 and 6.44 μM, respectively. Molecular docking and dynamics of inhibition of the S protein and Mpro by NZO and DMO correlated well. Docking of the six-hit secoiridoids to IL1R, IL6R, and TNFR1, the receptors of inflammatory cytokines IL1β, IL6, and TNFα, revealed the anti-inflammatory potential except for DHO. Due to intricate structures, the secoiridoids violated Lipinski's rule of five. However, the drug scores of secoiridoids supported their use as drugs. The ADMET predictions implied that the secoiridoids are non-toxic and pose low oral absorption. Secoiridoids need further optimization and are a suitable lead for the discovery of anti-SARS-CoV-2 therapeutics. For the moment, olive secoiridoids presents an accessible mode of prevention and therapy of SARS-CoV-2 infection.

scholarly journals Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski’s Rule of Five and ZINC Databank

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Pablo Andrei Nogara ◽  
Rogério de Aquino Saraiva ◽  
Diones Caeran Bueno ◽  
Lílian Juliana Lissner ◽  
Cristiane Lenz Dalla Corte ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Ache Activity ◽  
Acetylcholinesterase Inhibitors ◽  
Behavioral Changes ◽  
Lipinski’S Rule ◽  
Memory Impairments ◽  
Compound C ◽  
Lipinski’S Rule Of Five

Alzheimer’s disease (AD) is a progressive and neurodegenerative pathology that can affect people over 65 years of age. It causes several complications, such as behavioral changes, language deficits, depression, and memory impairments. One of the methods used to treat AD is the increase of acetylcholine (ACh) in the brain by using acetylcholinesterase inhibitors (AChEIs). In this study, we used the ZINC databank and the Lipinski’s rule of five to perform a virtual screening and a molecular docking (using Auto Dock Vina 1.1.1) aiming to select possible compounds that have quaternary ammonium atom able to inhibit acetylcholinesterase (AChE) activity. The molecules were obtained by screening and furtherin vitroassays were performed to analyze the most potent inhibitors through the IC50value and also to describe the interaction models between inhibitors and enzyme by molecular docking. The results showed that compound D inhibited AChE activity from different vertebrate sources and butyrylcholinesterase (BChE) fromEquus ferus(EfBChE), with IC50ranging from 1.69 ± 0.46 to 5.64 ± 2.47 µM. Compound D interacted with the peripheral anionic subsite in both enzymes, blocking substrate entrance to the active site. In contrast, compound C had higher specificity as inhibitor ofEfBChE. In conclusion, the screening was effective in finding inhibitors of AChE and BuChE from different organisms.

scholarly journals Interactions of Alkyl Gallates with SARS-CoV-2 Main Protease: A Molecular Docking Approach

2020 ◽  
Vol 3 (1) ◽  
pp. 9
Author(s):  
Amalia Stefaniu ◽  
Lucia Pintilie ◽  
Bujor Albu ◽  
Lucia Pirvu
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Synthetic Compounds ◽  
X Ray ◽  
Lipinski’S Rule ◽  
Alkyl Gallates ◽  
Main Protease ◽  
Docking Approach ◽  
Lipinski’S Rule Of Five ◽  
In Silico Methods

Ten natural and semi-synthetic compounds (gallic acid and alkyl gallates) were investigated by in silico methods in order to evaluate their potential inhibitory activity against SAR-CoV-2 using the X-ray structure of SARS-CoV-2 main protease bound to Boceprevir at 1.45 Å (PDB ID: 6WNP). The evaluation of drug-likeness in terms of Lipinski’s Rule of Five and docking results in terms of docking score and interactions with the amino acids residues from the active binding site of the target protein were reported.

scholarly journals Computational analysis by molecular docking of thirty alkaloid compounds from medicinal plants as potent inhibitors of SARS-CoV-2 main protease

2021 ◽  
Vol 4 (4) ◽  
pp. 487-503
Author(s):  
Tunga Kuhana A ◽  
◽  
Jason T. Kilembe ◽  
Aristote Matondo ◽  
Khamis M. Yussuf ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Medicinal Plants ◽  
Computational Analysis ◽  
Potential Drug ◽  
Lipinski’S Rule ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Potential Inhibitors ◽  
Therapeutic Profile

Year 2020 has been highly affected by the COVID-19 outbreak. The urgent need for a potent and effective drug for the treatment of this malignancy put pressure on researchers and scientists worldwide to develop a potential drug or a vaccine to resist SARS-CoV-2 virus. We report in this paper the assessment of the efficiency of thirty alkaloid compounds derived from African medicinal plants against the SARS-CoV-2 main protease through molecular docking and bioinformatics approaches. The results revealed four potential inhibitors (ligands 18, 21, 23 and 24) with 12.26 kcal/mol being the highest binding energy. Additionally, in silico drug-likeness and ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) properties for the four ligands showed a good predicted therapeutic profile of druggability, and fully obey the Lipinski's rule of five as well.

scholarly journals Natural xanthone compounds as promising drug candidates against COVID-19 - An integrated molecular docking and dynamics simulation study

2020 ◽  
Author(s):  
Shravan Kumar Gunda ◽  
Hima Kumari P ◽  
Gourav Choudhir ◽  
Anuj Kumar ◽  
P B. Kavi Kishor ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antiviral Agents ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Lipinski’S Rule ◽  
Drug Candidates ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Dynamics Simulations ◽  
Potential Inhibitors

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease2019 (COVID-19). SARS-CoV-2 is known for its high pathogenicity and transmission due to thepresence of polybasic cleavage sites. No specific drug is available for the treatment. To identifythe potential inhibitors, we have performed molecular docking against the SARS-CoV-2 mainprotease (6Y84) with fifteen important natural xanthone compounds. The docking results showedall the compounds exhibited good binding energies and interactions with the main protease. Thevalidation of representative docking complexes through molecular dynamics simulations showedthat xanthones binds with a higher binding affinity and lower free energy than the standardligand with Brasixanthone C and Brasixanthone B on 50 ns. Natural xanthone compounds havealso passed the Absorption, Distribution, Metabolism, and Excretion (ADME) property criteriaas well as Lipinski’s rule of five. The present integrated molecular docking and dynamicssimulations study unveil the use of xanthones as potential antiviral agents against SARS-CoV-2.

scholarly journals In silico study on anti-Chikungunya virus activity of hesperetin

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2602 ◽  
Author(s):  
Adrian Oo ◽  
Pouya Hassandarvish ◽  
Sek Peng Chin ◽  
Vannajan Sanghiran Lee ◽  
Sazaly Abu Bakar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chikungunya Virus ◽  
Md Simulations ◽  
Inhibitory Effect ◽  
Structural Proteins ◽  
In Vitro Screening ◽  
Intracellular Replication ◽  
Lipinski’S Rule ◽  
Lipinski’S Rule Of Five

BackgroundThe re-emerging,Aedes spp.transmitted Chikungunya virus (CHIKV) has recently caused large outbreaks in a wide geographical distribution of the world including countries in Europe and America. Though fatalities associated with this self-remitting disease were rarely reported, quality of patients’ lives have been severely diminished by polyarthralgia recurrence. Neither effective antiviral treatment nor vaccines are available for CHIKV. Our previous in vitro screening showed that hesperetin, a bioflavonoid exhibits inhibitory effect on the virus intracellular replication. Here, we present a study using the computational approach to identify possible target proteins for future mechanistic studies of hesperetin.Methods3D structures of CHIKV nsP2 (3TRK) and nsP3 (3GPG) were retrieved from Protein Data Bank (PDB), whereas nsP1, nsP4 and cellular factor SPK2 were modeled using Iterative Threading Assembly Refinement (I-TASSER) server based on respective amino acids sequence. We performed molecular docking on hesperetin against all four CHIKV non-structural proteins and SPK2. Proteins preparation and subsequent molecular docking were performed using Discovery Studio 2.5 and AutoDock Vina 1.5.6. The Lipinski’s values of the ligand were computed and compared with the available data from PubChem. Two non-structural proteins with crystal structures 3GPG and 3TRK in complexed with hesperetin, demonstrated favorable free energy of binding from the docking study, were further explored using molecular dynamics (MD) simulations.ResultsWe observed that hesperetin interacts with different types of proteins involving hydrogen bonds, pi-pi effects, pi-cation bonding and pi-sigma interactions with varying binding energies. Among all five tested proteins, our compound has the highest binding affinity with 3GPG at −8.5 kcal/mol. The ligand used in this study also matches the Lipinski’s rule of five in addition to exhibiting closely similar properties with that of in PubChem. The docking simulation was performed to obtain a first guess of the binding structure of hesperetin complex and subsequently analysed by MD simulations to assess the reliability of the docking results. Root mean square deviation (RMSD) of the simulated systems from MD simulations indicated that the hesperetin complex remains stable within the simulation timescale.DiscussionThe ligand’s tendencies of binding to the important proteins for CHIKV replication were consistent with our previous in vitro screening which showed its efficacy in blocking the virus intracellular replication. NsP3 serves as the highest potential target protein for the compound’s inhibitory effect, while it is interesting to highlight the possibility of interrupting CHIKV replication via interaction with host cellular factor. By complying the Lipinski’s rule of five, hesperetin exhibits drug-like properties which projects its potential as a therapeutic option for CHIKV infection.

scholarly journals Molecular docking, chemo-informatic properties, alpha-amylase, and lipase inhibition studies of benzodioxol derivatives

BMC Chemistry ◽  
2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Mohammed Hawash ◽  
Nidal Jaradat ◽  
Suhaib Shekfeh ◽  
Murad Abualhasan ◽  
Ahmad M. Eid ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Alpha Amylase ◽  
In Vivo Evaluation ◽  
Lipinski’S Rule ◽  
Drug Candidates ◽  
Lead Compounds ◽  
Lipase Enzyme ◽  
Lipinski’S Rule Of Five

AbstractCurrently, available therapies for diabetes could not achieve normal sugar values in a high percentage of treated patients. In this research project, a series of 17 benzodioxole derivatives were evaluated as antidiabetic agents; that belong to three different groups were evaluated against lipase and alpha-amylase (α-amylase) enzymes. The results showed that 14 compounds have potent inhibitory activities against α-amylase with IC50 values below 10 µg/ml. Among these compounds, 4f was the most potent compound with an IC50 value of 1.11 µg/ml compared to the anti-glycemic agent acarbose (IC50 6.47 µg/ml). On the contrary, these compounds showed weak or negligible activities against lipase enzyme. However, compound 6a showed the best inhibitory anti-lipase activity with IC50 44.1 µg/ml. Moreover, all the synthesized compounds were undergone Molinspiration calculation, and the result showed that all compounds obeyed Lipinski’s rule of five. Molecular docking studies were performed to illustrate the binding interactions between the benzodioxole derivatives and α-amylase enzyme pocket. Related to the obtained results it was clear that the carboxylic acid, benzodioxole ring, halogen or methoxy substituted aryl are important for the anti-amylase activities. The potent inhibitory results of some of the synthesized compounds suggest that these molecules should go further in vivo evaluation. It also suggests the benzodioxole derivatives as lead compounds for developing new drug candidates.

Sign in / Sign up

Export Citation Format

Share Document