Essential oils of Uvaria boniana – chemical composition, in vitro bioactivity, docking, and in silico ADMET profiling of selective major compounds

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Son Ninh The ◽  
Anh Le Tuan ◽  
Thuy Dinh Thi Thu ◽  
Luyen Nguyen Dinh ◽  
Tuyen Tran Thi ◽  
...  
Keyword(s):  
Essential Oils ◽  
In Silico ◽  
Oral Absorption ◽  
Binding Protein ◽  
Binding Energies ◽  
Penicillin Binding Protein ◽  
Bv2 Cells ◽  
In Silico Admet ◽  
Leaf Oil

Abstract Phytochemical investigation applying GC (gas chromatography)-MS (mass spectrometry)/GC-FID (flame ionization detection) on the hydro-distilled essential oils of the Vietnamese medicinal plant Uvaria boniana leaf and twig lead to the detection of 35 constituents (97.36%) in the leaf oil and 52 constituents (98.75%) in the twig oil. Monoterpenes, monoterpenoids, sesquiterpenes, and sesquiterpenoids were characteristic of U. boniana essential oils. The leaf oil was represented by major components (E)-caryophyllene (16.90%), bicyclogermacrene (15.95%), α-humulene (14.96%), and linalool (12.40%), whereas four compounds α-cadinol (16.16%), epi-α-muurolol (10.19%), α-pinene (11.01%), and β-pinene (8.08%) were the main ones in the twig oil. As compared with the leaf oil, the twig oil was better in antimicrobial activity. With the same MIC value of 40 mg/mL, the twig oil successfully controlled the growth of Gram (+) bacterium Bacillus subtilis, Gram (−) bacterium Escherichia coli, fungus Aspergillus niger, and yeast Saccharomyces cerevisiae. In addition, both two oil samples have induced antiinflammatory activity with the IC50 values of 223.7–240.6 mg/mL in NO productive inhibition when BV2 cells had been stimulated by LPS. Docking simulations of four major compounds of U. boniana twig oil on eight relevant antibacterial targets revealed that epi-α-muurolol and α-cadinol are moderate inhibitors of E. coli DNA gyrase subunit B, penicillin binding protein 2X and penicillin binding protein 3 of Pseudomonas aeruginosa with similar free binding energies of −30.1, −29.3, and −29.3 kJ/mol, respectively. Furthermore, in silico ADMET studies indicated that all four docked compounds have acceptable oral absorption, low metabolism, and appropriated toxicological profile to be considered further as drug candidates.

Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Di-hydropyridine Analogs as Potent Antioxidants

2019 ◽  
Vol 19 (29) ◽  
pp. 2676-2686 ◽  
Author(s):  
Saddala Madhu Sudhana ◽  
Pradeepkiran Jangampalli Adi
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Binding Energies ◽  
Molecular Docking Studies ◽  
Metal Chelating ◽  
In Silico Admet ◽  
Dpph Method

Aims: The aim of this study is to synthesize, characterize and biological evaluation of 3-ethyl 5- methyl2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate derivatives. Background: An efficient synthesis of two series of novel carbamate and sulfonamide derivatives of amlodipine, 3-ethyl 5-methyl 2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (amlodipine) 1 were chemical synthesized process. Materials & Methods: In this process, various chloroformates 2(a-e) and sulfonyl chlorides 4(a-e) on reaction with 1 in the presence of N,N–dimethylpiperazine as a base in THF at 50-550 oC, the corresponding title compounds 3(a-e) and 5(a-e) in high yields. Furthermore, the compounds 3(a-e) and 5(a-e) were evaluated for antioxidant activity (DPPH method), metal chelating activity, hemolytic activity, antioxidant assay (ABTS method), cytotoxicity, molecular docking and in silico ADMET properties. Result: Results revealed that 5a, 5e, 3d, 3a and 5c exhibited high antioxidant, metal chelating activities, but 5a, 5e and 3d exhibited low activity. The molecular docking studies and ADMET of suggested ligands showed the best binding energies and non-toxic properties. Conclusion: The present in silico and in vitro evaluations suggested that these dihydropyridine derivatives act as potent antioxidants and chelating agents which may be useful in treating metals induced oxidative stress associated diseases.

scholarly journals Synthesis of novel ketene dithioacetals via one pot reaction: Molecular modelling in-silico Admet studies and antimicrobial activity

2021 ◽  
pp. 187-202
Author(s):  
Mohammad Arif Pasha ◽  
Sumanta Mondal ◽  
Naresh Panigrahi
Keyword(s):  
In Silico ◽  
Binding Energies ◽  
Inhibition Mechanism ◽  
Good Prediction ◽  
One Pot ◽  
Ketene Dithioacetals ◽  
In Silico Admet ◽  
In Silico Studies ◽  
Three Component Reaction

A simple and efficient method for the synthesis of fifteen novel ketene dithioacetals (2-(6-amino5-cyano-4-aryl-4H-1,3-dithiin-2-ylidene) malononitrile) via a one-pot three-component reaction of activated methylene group malononitrile with carbon disulfide in the presence of arylidene malononitriles were reported. The effects of LiOH.H2O as a base at different concentrations have been investigated and can provide products in good yields at 40-50ºC temperature (54-89%). All the synthesized ketene dithioacetals compounds (MCB1-MCB15) were checked for favorable pharmacokinetic param¬eters along with toxicities which are based on drug-likeness explained by Lipinski’s rule of five by Med chem designer software correlated with that of pkCSM online tool. Explorations of synthesized ketene dithioacetals compounds for the antimicrobial study were found to be effective towards Staphylococcus aureus (MCB5 and MCB13) with a zone of inhibition at 26mm and 22mm which is compared to that of standard ciprofloxacin (26mm). This made our study to explore the inhibition mechanism with the help of molecular docking studies with possible binding energies (-6.4 to -8.9 kJ/mol) by pyrx 0.8 software to represent a good prediction of interactions between the ligand and protein (2XCT). Further evaluation of druggability and ADMET predictions compounds MCB5 and MCB13 were found to be effective. Based on the in-vitro and in-silico studies a series of ketene dithioacetals compounds may be helpful for further studying SAR and designing more potent antimicrobials.

In Silico Appraisal, Synthesis, Antibacterial Screening and DNA Cleavage for 1,2,5-thiadiazole Derivative

2019 ◽  
Vol 15 (5) ◽  
pp. 445-455 ◽  
Author(s):  
Suraj N. Mali ◽  
Sudhir Sawant ◽  
Hemchandra K. Chaudhari ◽  
Mustapha C. Mandewale
Keyword(s):  
Molecular Docking ◽  
Dna Cleavage ◽  
In Silico ◽  
Oral Absorption ◽  
Inhibition Mechanism ◽  
Hydrogen Binding ◽  
Docking Score ◽  
Antibacterial Screening ◽  
Mycobacteria Tuberculosis

Background: : Thiadiazole not only acts as “hydrogen binding domain” and “two-electron donor system” but also as constrained pharmacophore. Methods:: The maleate salt of 2-((2-hydroxy-3-((4-morpholino-1, 2,5-thiadiazol-3-yl) oxy) propyl) amino)- 2-methylpropan-1-ol (TML-Hydroxy)(4) has been synthesized. This methodology involves preparation of 4-morpholino-1, 2,5-thiadiazol-3-ol by hydroxylation of 4-(4-chloro-1, 2,5-thiadiazol-3-yl) morpholine followed by condensation with 2-(chloromethyl) oxirane to afford 4-(4-(oxiran-2-ylmethoxy)-1,2,5-thiadiazol- 3-yl) morpholine. Oxirane ring of this compound was opened by treating with 2-amino-2-methyl propan-1- ol to afford the target compound TML-Hydroxy. Structures of the synthesized compounds have been elucidated by NMR, MASS, FTIR spectroscopy. Results: : The DSC study clearly showed that the compound 4-maleate salt is crystalline in nature. In vitro antibacterial inhibition and little potential for DNA cleavage of the compound 4 were explored. We extended our study to explore the inhibition mechanism by conducting molecular docking, ADMET and molecular dynamics analysis by using Schrödinger. The molecular docking for compound 4 showed better interactions with target 3IVX with docking score of -8.508 kcal/mol with respect to standard ciprofloxacin (docking score= -3.879 kcal/mol). TML-Hydroxy was obtained in silico as non-carcinogenic and non-AMES toxic with good percent human oral absorption profile (69.639%). TML-Hydroxy showed the moderate inhibition against Mycobacteria tuberculosis with MIC 25.00 μg/mL as well as moderate inhibition against S. aureus, Bacillus sps, K. Pneumoniae and E. coli species. Conclusion: : In view of the importance of the 1,2,5-thiadiazole moiety involved, this study would pave the way for future development of more effective analogs for applications in medicinal field.

Virtual Screening, Molecular docking and in-silico ADME-Tox analysis for identification of potential main protease (Mpro) enzyme inhibitors

2020 ◽  
Vol 18 ◽  
Author(s):  
Debadash Panigrahi ◽  
Ganesh Prasad Mishra
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Data Bank ◽  
Future Research ◽  
Reference Compound ◽  
Unexpected Death ◽  
Main Protease ◽  
In Silico Admet

Objective:: Recent pandemic caused by SARS-CoV-2 described in Wuhan China in December-2019 spread widely almost all the countries of the world. Corona virus (COVID-19) is causing the unexpected death of many peoples and severe economic loss in several countries. Virtual screening based on molecular docking, drug-likeness prediction, and in silico ADMET study has become an effective tool for the identification of small molecules as novel antiviral drugs to treat diseases. Methods:: In the current study, virtual screening was performed through molecular docking for identifying potent inhibitors against Mpro enzyme from the ZINC library for the possible treatment of COVID-19 pandemic. Interestingly, some compounds are identified as possible anti-covid-19 agents for future research. 350 compounds were screened based on their similarity score with reference compound X77 from ZINC data bank and were subjected to docking with crystal structure available of Mpro enzyme. These compounds were then filtered by their in silico ADME-Tox and drug-likeness prediction values. Result:: Out of these 350 screened compounds, 10 compounds were selected based on their docking score and best docked pose in comparison to the reference compound X77. In silico ADME-Tox and drug likeliness predictions of the top compounds were performed and found to be excellent results. All the 10 screened compounds showed significant binding pose with the target enzyme main protease (Mpro) enzyme and satisfactory pharmacokinetic and toxicological properties. Conclusion:: Based on results we can suggest that the identified compounds may be considered for therapeutic development against the COVID-19 virus and can be further evaluated for in vitro activity, preclinical, clinical studies and formulated in a suitable dosage form to maximize their bioavailability.

scholarly journals PenA, a penicillin-binding protein-type thioesterase specialized for small peptide cyclization

2021 ◽  
Author(s):  
Kenichi Matsuda ◽  
Kei Fujita ◽  
Toshiyuki Wakimoto
Keyword(s):  
Enzymatic Activity ◽  
Computational Model ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Small Peptide ◽  
Peptide Cyclization ◽  
Chain Lengths ◽  
Non Ribosomal Peptides

Abstract Penicillin binding protein-type thioesterases (PBP-type TEs) are a recently identified group of peptide cyclases that catalyze head-to-tail macrolactamization of non-ribosomal peptides. PenA, a new member of this group, is involved in the biosyntheses of cyclic pentapeptides. In this study, we demonstrated the enzymatic activity of PenA in vitro, and analyzed its substrate scope with a series of synthetic substrates. A comparison of the reaction profiles between PenA and SurE, a representative PBP-type TE, showed that PenA is more specialized for small peptide cyclization. A computational model provided a possible structural rationale for the altered specificity for substrate chain lengths.

scholarly journals Comparative Study on the Essential Oils from Five Wild Egyptian Centaurea Species: Effective Extraction Techniques, Antimicrobial Activity and In-Silico Analyses

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 252
Author(s):  
Eman H. Reda ◽  
Zienab T. Abdel Shakour ◽  
Ali M. El-Halawany ◽  
El-Sayeda A. El-Kashoury ◽  
Khaled A. Shams ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Essential Oils ◽  
In Silico ◽  
Folk Medicine ◽  
Principal Component ◽  
Binding Pocket ◽  
Green Technologies ◽  
Sample Classification ◽  
Docking Approach

The genus Centaurea is recognized in folk medicine for anti-inflammatory, anti-itch, antitussive, purgative, astringent, and tonic activities. To study the chemical determinant for antimicrobial activity essential oils (EOs), five Centaurea species were analyzed including: C. scoparia, C. calcitrapa, C. glomerata, C. lipii and C. alexandrina. Conventional hydro-distillation (HD) and microwave-assisted extraction (MAE), as new green technologies, were compared for the extraction of essential oils. GC/MS analysis identified 120 EOs including mostly terpenoid except from C. lipii and C. alexandrina in which nonterpenoids were the major constituents. Major terpenoids included spathulenol, caryophyllene oxide and alloaromadendrene oxide-2. To probe antibacterial activity, potential EO inhibitors of a bacterial type II DNA topoisomerase, DNA gyrase B were screened via an in silico molecular docking approach. Spathulenol and alloaromadendrene oxide-2 possessed the best binding affinity in the ATP- binding pocket of Gyrase B enzyme. Principal component analysis and agglomerative hierarchical clustering were used for sample classification and revealed that sesquiterpenes contributed the most for accessions classification. In vitro antimicrobial activity against Staphylococcus aureus, Escherichia coli and Aspergillus niger for all EOs were also evaluated. EOs from C. lipii, C. glomerata and C. calcitrapa exhibited significant MIC against S. aureus with an MIC value of 31.25 µg/mL.

scholarly journals Predicting Absorption-Distribution Properties of Neuroprotective Phosphine-Borane Compounds Using In Silico Modeling and Machine Learning

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2505
Author(s):  
Raheem Remtulla ◽  
Sanjoy Kumar Das ◽  
Leonard A. Levin
Keyword(s):  
Machine Learning ◽  
Neural Networks ◽  
In Silico ◽  
Disulfide Bonds ◽  
Oral Absorption ◽  
In Vivo Studies ◽  
Drug Candidates ◽  
In Silico Methods

Phosphine-borane complexes are novel chemical entities with preclinical efficacy in neuronal and ophthalmic disease models. In vitro and in vivo studies showed that the metabolites of these compounds are capable of cleaving disulfide bonds implicated in the downstream effects of axonal injury. A difficulty in using standard in silico methods for studying these drugs is that most computational tools are not designed for borane-containing compounds. Using in silico and machine learning methodologies, the absorption-distribution properties of these unique compounds were assessed. Features examined with in silico methods included cellular permeability, octanol-water partition coefficient, blood-brain barrier permeability, oral absorption and serum protein binding. The resultant neural networks demonstrated an appropriate level of accuracy and were comparable to existing in silico methodologies. Specifically, they were able to reliably predict pharmacokinetic features of known boron-containing compounds. These methods predicted that phosphine-borane compounds and their metabolites meet the necessary pharmacokinetic features for orally active drug candidates. This study showed that the combination of standard in silico predictive and machine learning models with neural networks is effective in predicting pharmacokinetic features of novel boron-containing compounds as neuroprotective drugs.

scholarly journals Studi Interaksi Molekuler Aktivitas Antimikroba Peptida Bioaktif terhadap Staphylococcus aureus Secara In silico

2020 ◽  
Vol 7 (2) ◽  
pp. 93
Author(s):  
Taufik Muhammad Fakih ◽  
Mentari Luthfika Dewi
Keyword(s):  
Staphylococcus Aureus ◽  
In Silico ◽  
Binding Protein ◽  
Pelteobagrus Fulvidraco ◽  
Penicillin Binding Protein ◽  
Discovery Studio

Pendahuluan: Lendir kulit ikan lele kuning (Pelteobagrus fulvidraco), mengandung peptida bioaktif dan banyak dimanfaatkan dalam pengobatan berbagai penyakit karena memiliki aktivitas biologis, diantaranya sebagai antimikroba. Beberapa peptida bioaktif tersebut, antara lain pelteobagrin, myxinidin, pleurocidin, dan pardaxin-P1 dan telah terbukti mampu menghambat Penicillin-Binding Protein 3 (PBP3) dari Staphylococcus aureus. Tujuan: Penelitian ini bertujuan untuk mengidentifikasi aktivitas antimikroba molekul peptida bioaktif secara in silico terhadap makromolekul Penicillin-Binding Protein 3 (PBP3) dari Staphylococcus aureus dan interaksi peptida bioaktif tersebut yang terlibat dalam mekanisme aksi antimikroba. Metode: Sekuensing peptida bioaktif terlebih dahulu dilakukan pemodelan ke dalam bentuk konformasi 3D menggunakan software PEP-FOLD. Konformasi terbaik hasil pemodelan dipilih untuk kemudian dilakukan studi penambatan molekuler terhadap makromolekul dari Staphylococcus aureus menggunakan software PatchDock. Interaksi molekuler yang terbentuk selanjutnya diidentifikasi lebih lanjut menggunakan software BIOVIA Discovery Studio 2020. Hasil: Berdasarkan hasil penambatan molekuler menunjukkan bahwa peptida bioaktif myxinidin memiliki afinitas paling baik dengan ACE score −2497,26 kJ/mol. Kesimpulan: Peptida bioaktif lendir kulit ikan lele kuning (Pelteobagrus fulvidraco) dapat dipertimbangkan sebagai kandidat antimikroba alami.

scholarly journals Ficus benghalensis as Potential Inhibitor of 5α-Reductase for Hair Growth Promotion: In Vitro, In Silico, and In Vivo Evaluation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jawaria Iltaf ◽  
Sobia Noreen ◽  
Muhammad Fayyaz ur Rehman ◽  
Shazia Akram Ghumman ◽  
Fozia Batool ◽  
...  
Keyword(s):  
In Silico ◽  
Hair Growth ◽  
De Novo ◽  
Growth Promotion ◽  
Hair Follicles ◽  
Binding Energies ◽  
Ficus Benghalensis ◽  
Rp Hplc

The screening of hair follicles, dermal papilla cells, and keratinocytes through in vitro, in vivo, and histology has previously been reported to combat alopecia. Ficus benghalensis has been used conventionally to cure skin and hair disorders, although its effect on 5α-reductase II is still unknown. Currently, we aim to analyze the phytotherapeutic impact of F. benghalensis leaf extracts (FBLEs) for promoting hair growth in rabbits along with in vitro inhibition of the steroid isozyme 5α-reductase II. The inhibition of 5α-reductase II by FBLEs was assessed by RP-HPLC, using the NADPH cofactor as the reaction initiator and Minoxin (5%) as a positive control. In silico studies were performed using AutoDock Vina to visualize the interaction between 5α-reductase II and the reported phytoconstituents present in FBLEs. Hair growth in female albino rabbits was investigated by applying an oral dose of the FBLE formulation and control drug to the skin once a day. The skin tissues were examined by histology to see hair follicles. Further, FAAS, FTIR, and antioxidants were performed to check the trace elements and secondary metabolites in the FBLEs. The results of RP-HPLC and the binding energies showed that FBLEs reduced the catalytic activity of 5α-reductase II and improved cell proliferation in rabbits. The statistical analysis (p < 0.05 or 0.01) and percentage inhibition (>70%) suggested that hydroalcoholic FBLE has more potential in increasing hair growth by elongating hair follicle’s anagen phase. FAAS, FTIR, and antioxidant experiments revealed sufficient concentrations of Zn, Cu, K, and Fe, together with the presence of polyphenols and scavenging activity in FBLE. Overall, we found that FBLEs are potent in stimulating hair follicle maturation by reducing the 5α-reductase II action, so they may serve as a principal choice in de novo drug designing to treat hair loss.

Anti-Proliferative Activity of Piper trioicum Leaf Essential Oil Based on Phytoconstituent Analysis, Molecular Docking and In Silico ADMET Approaches

2021 ◽  
Vol 25 ◽  
Author(s):  
Sudipta Jena ◽  
Asit Ray ◽  
Ambika Sahoo ◽  
Prabhat Kumar Das ◽  
Pradeep Kumar Kamila ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chemical Composition ◽  
Essential Oil ◽  
Essential Oils ◽  
Cell Lines ◽  
In Silico ◽  
Proliferative Activity ◽  
In Silico Admet ◽  
Leaf Essential Oil ◽  
Ht 29

Background: The essential oils isolated from several medicinal plants are reported to have anticancer activities. Both the essential oil and extracts of many Piper species (Piperaceae) possess potential cytotoxic effect against cancer cell lines and are being used in traditional system of medicine for the treatment of cancer. There is a need to evaluate and validate the anticancer properties of essential oils extracted from other wild species of Piper. Objective: The current research was undertaken to determine the chemical composition and investigate the anti-proliferative activity of wild growing Piper trioicum leaf essential oil. The selected five major constituents were subjected to molecular docking to identify possible modes of binding against serine/threonine-protein kinase (MST3) protein Methods: The essential oil of leaf of P. trioicum was extracted by hydro distillation method and its chemical composition was carried out by GC-FID and GC-MS. The anti-proliferative activity of the essential oil was evaluated by MTT assay against normal (3T3-L1) and various cancer (HCT 116, HT-29, PC-3 and HepG2) cell lines. Molecular docking analysis was performed using AutoDock 4.2 software. The pharmacokinetic and pharmacodynamic properties of the major constituents were determined using absorption, distribution, metabolization, excretion and toxicity (ADMET) analysis. Results: The GC-MS analysis revealed the identification of 45 constituents with δ-cadinene (19.57%), germacrene-D (8.54%), β-caryophyllene (6.84%), 1-epi-cubenol (4.83%) and α-pinene (4.52%) were found to be predominant constituents in the leaf essential oil of P. trioicum. The highest cytotoxicity of essential oil was observed against HT-29 cells (IC50 value of 33.14 µg/ml). 1-epi-cubenol and δ-Cadinene exhibited low binding energy values of -6.25 and -5.92 kcal/mol, respectively. For prediction of in silico pharmacokinetic and druglike properties of the major compounds, ADMET prediction tool was also used, the results of which came within the ideal range. Conclusion: The present findings demonstrated that P. trioicum essential oil possesses significant anti-proliferative activity and could be effective against cancer treatment.

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