In vitro and in silico studies of two 1,4-naphthoquinones and their topical formulation in bigels

2021 ◽  
Vol 18 ◽  
Author(s):  
Imen Khelifi ◽  
Audrey Tourrette ◽  
Daycem Khelifi ◽  
Thomas Efferth ◽  
El Akrem Hayouni ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Water Solubility ◽  
Biological Activities ◽  
Binding Energies ◽  
Topical Formulation ◽  
Plant Metabolites ◽  
Secondary Plant Metabolites ◽  
In Silico Studies

Background: 1,4-Naphthoquinones (1,4-NQs) are secondary plant metabolites with numerous biological activities. 1,4-NQs display low water solubility and poor bioavailability. Bigels are a new technology with great potential, which are designated as drug delivery systems. Biphasic bigels consisting of solid and liquid components represent suitable formulations improving the diffusion and bioavailability of NQs into the skin. Objective: We evaluated the in silico and in vitro activity of 5,8-dihydroxy-1,4-naphthoquinone (M1) and 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (M2) on elastase and assessed their cytotoxicity towards COLO38 melanoma cells. The 1,4-NQs were loaded into bigels for topical application. Methods: Molecular docking was performed, and cytotoxicity was evaluated on COLO38 cells using the resazurin assay. M1 and M2 were separately incorporated into bigels consisting of hydrogel organogel with sweet almond oil as a non-polar solvent and span 65 as organogelator. Their rheological behavior and microscopic properties were characterized. The diffusion kinetics and permeation of 1,4-NQs from bigels were studied by a paddle-over-extraction cell and a “Franz cell” in vitro permeation model. Results: Molecular docking data predicted high interactions between elastase and ligands. Hydrogen bonds to LYS233 were observed for M1, M2, and phosphoramidon (positive control). The average binding energies were -8.5 and -9.7 kcal/mol for M1 and M2 and -12.6 kcal/mol for phosphoramidon. M1 and M2 inhibited the elastase activity by 58.9 and 56.6%, respectively. M1 and M2 were cytotoxic towards COLO38 cells (IC50: 2.6 and 9.8 µM) y. The M1 release from bigels was faster and more efficient than that of M2. Conclusion: M1 and M2 are promising for skin disease treatment. Biphasic organogel-hydrogel bigels are efficient and safe formulations to overcome their low bioavailability.

Chalcones: As potent α-amylase enzyme inhibitors; synthesis, in vitro, and in silico studies

2020 ◽  
Vol 16 ◽  
Author(s):  
Mahboob Ali ◽  
Momin Khan ◽  
Khair Zaman ◽  
Abdul Wadood ◽  
Maryam Iqbal ◽  
...  
Keyword(s):  
In Silico ◽  
Enzyme Inhibitors ◽  
Biological Activities ◽  
Condensation Reaction ◽  
Type Ii Diabetes Mellitus ◽  
Spectroscopic Techniques ◽  
Chalcone Derivatives ◽  
In Silico Studies ◽  
Wide Range

: Background: The inhibition of α-amylase enzyme is one of the best therapeutic approach for the management of type II diabetes mellitus. Chalcone possesses a wide range of biological activities. Objective: In the current study chalcone derivatives (1-17) were synthesized and evaluated their inhibitory potential against α-amylase enzyme. Method: For that purpose, a library of substituted (E)-1-(naphthalene-2-yl)-3-phenylprop-2-en-1-ones was synthesized by ClaisenSchmidt condensation reaction of 2-acetonaphthanone and substituted aryl benzaldehyde in the presence of base and characterized via different spectroscopic techniques such as EI-MS, HREI-MS, 1H-, and 13C-NMR. Results: Sixteen synthetic chalcones were evaluated for in vitro porcine pancreatic α-amylase inhibition. All the chalcones demonstrated good inhibitory activities in the range of IC50 = 1.25 ± 1.05 to 2.40 ± 0.09 μM as compared to the standard commercial drug acarbose (IC50 = 1.34 ± 0.3 μM). Conclusion: Chalcone derivatives (1-17) were synthesized, characterized, and evaluated for their α-amylase inhibition. SAR revealed that electron donating groups in the phenyl ring have more influence on enzyme inhibition. However, to insight the participation of different substituents in the chalcones on the binding interactions with the α-amylase enzyme, in silico (computer simulation) molecular modeling analyses were carried out.

scholarly journals Computer-Based Approaches for Determining the Pharmacological Profile of 5-(3-Nitro-Arylidene)-Thiazolidine-2,4-Dione

2021 ◽  
Vol 11 (6) ◽  
pp. 13806-13828
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Density Functional ◽  
Biological Activities ◽  
Computational Approach ◽  
Basis Set ◽  
Pharmacological Profile ◽  
Dft Methods ◽  
Starting Point ◽  
In Silico Studies

The development of novel and safe compounds is a challenging task in the drug discovery trajectory. Accordingly, the individuation of promising core molecules with biological activities could pave the way to develop effective drugs to treat a given disease. The use of a computational approach can reduce the time for identifying promising core molecules characterizing their potential pharmacological profile and providing hints for the synthesis of novel derivatives with increased predicted pharmacological activity. Following this strategy, starting from a core molecule thiazolidine-2,4-dione, the derivative of 5-(3-nitro-arylidene)-thiazolidine-2,4-dione was synthesized to investigate the biological and pharmacological potential. An extensive computational investigation was performed employing ab initio calculations by using Density Functional Theory (DFT), and subsequent in silico studies were accomplished by molecular docking calculation. The structures 5-(3-nitro-arylidene)-thiazolidine-2,4-dione were fully optimized using multiparametric DFT methods were calculated at the B3LYP/6-31+G (d, p) level basis set. Besides gaining insights into the potential pharmacological profile of the selected derivative, molecular docking against some selected drug targets, ADME, and PASS prediction were performed. According to charges and molecular electrostatic potential (MESP) calculation, the N-H region could offer promising active site interactions for protein binding. Furthermore, Homo-Lumo and global reactivity values indicate a good profile for the selected compound, and UV-Vis provides further insights about its properties, potentially helpful for further experimental analysis. Notably, the in silico investigation indicated that EGFR and ORF2 enzymes could represent the selected drug-like compound's possible targets. Conclusively, the proposed computational approach demonstrated that it is possible to evaluate a proposed compound's bioactivity profile. We characterized 5-(3-nitro-arylidene)-thiazolidine-2,4-dione derivative, suggesting it as a good starting point for developing interesting hit compounds with a relevant pharmacological profile.

scholarly journals Investigation of biological activities of Colocasia gigantea Hook.f. leaves and PASS prediction, in silico molecular docking with ADME/T analysis of its isolated bioactive compounds

2020 ◽  
Author(s):  
Safaet Alam ◽  
Nazim Uddin Emon ◽  
Mohammad A. Rashid ◽  
Mohammad Arman ◽  
Mohammad Rashedul Haque
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
In Silico ◽  
Castor Oil ◽  
Biological Activities ◽  
Kappa Opioid Receptor ◽  
Soluble Extract ◽  
Docking Score

AbstractBackgroundColocasia gigantea is locally named as kochu and also better known due to its various healing power. This research is to investigate the antidiarrheal, antimicrobial, and antioxidant possibilities of the methanol soluble extract of Colocasia gigantea.MethodsAntidiarrheal investigation was performed by using in vivo castor oil induced diarrheal method where as in vitro antimicrobial and antioxidant investigation have been implemented by disc diffusion and DPPH scavenging method respectively. Moreover, in silico studies were followed by molecular docking analysis of several secondary metabolites were appraised with Schrödinger-Maestro v 11.1.ResultsThe induction of plant extract (200 and 400 mg/kg, b.w, p.o), the castor oil mediated diarrhea has been minimized 19.05 % (p < 0.05) and 42.86 % (p < 0.001) respectively. The methanolic extract of C. gigantea showed mild sensitivity against almost all the tested strains but it shows high consistency of phenolic content and furthermore yielded 67.68 μg/mL of IC50 value in the DPPH test. The higher and lower binding affinity was shown in beta-amyrin and monoglyceryl stearic acid against the kappa-opioid receptor (PDB ID: 4DJH) with a docking score of -3.28 kcal/mol and -6.64 kcal/mol respectively. In the antimicrobial investigation, Penduletin and Beta-Amyrin showed the highest and lowest binding affinity against the selected receptors with the docking score of -8.27 kcal/mol and -1.66 kcal/mol respectively.ConclusionThe results of our scientific research reflect that the methanol soluble extract of C. gigantea is safe which may provide possibilities of alleviation of diarrhea and as a potential wellspring of antioxidants which can be considered as an alternate source for exploration of new medicinal products.

scholarly journals In Silico Drug Discovery of 4-Hyroxypanduratin A, 6-Gingerol and Luteolin Targeting Nipah Virus

2021 ◽  
pp. 477-484
Author(s):  
Anurag Verma ◽  
Piyush Mittal ◽  
Milind S. Pande ◽  
Neelanchal Trivedi
Keyword(s):  
Fusion Protein ◽  
In Silico ◽  
Virus Entry ◽  
Nipah Virus ◽  
Binding Energies ◽  
Viral Agent ◽  
In Silico Studies ◽  
Viral Target ◽  
Dietary Food

Nipah Virus is a zoo tonic virus and has re-emerged again with more deadliness. NiV has infected many animals and humans worldwide and a huge loss to life has been faced. NiV contains a Fusion protein on its outer membrane which helps in the virus entry into the host cell. This fusion protein is a virulent factor and is a major anti-viral target. Many medicinal plants have been used against viral diseases, current research aims towards the potential of three daily dietary food elements that can be used as an anti-viral agent. In-silico studies are performed with 4-hyroxypanduratin A, 6-gingerol and Luteolin against the NiV-F and binding energies were calculated. It was reported that these phyto-compounds have good negative binding energies and they have the promising potential against Nipah Virus. Further in-vitro research can be performed with these phyto-compounds to design a specific drug against Nipah Virus.

scholarly journals In Silico Studies of Tumor Targeted Peptide-Conjugated Natural Products for Targeting Over-Expressed Receptors in Breast Cancer Cells Using Molecular Docking, Molecular Dynamics and MMGBSA Calculations

2022 ◽  
Vol 12 (1) ◽  
pp. 515
Author(s):  
Lucy R. Hart ◽  
Charlotta G. Lebedenko ◽  
Saige M. Mitchell ◽  
Rachel E. Daso ◽  
Ipsita A. Banerjee
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
In Silico ◽  
Point Mutations ◽  
Binding Energies ◽  
Peptide Sequence ◽  
Peroxisome Proliferator ◽  
Peptide Conjugates ◽  
Biological Studies ◽  
In Silico Studies

In this work, in silico studies were carried out for the design of diterpene and polyphenol-peptide conjugates to potentially target over-expressed breast tumor cell receptors. Four point mutations were induced into the known tumor-targeting peptide sequence YHWYGYTPQN at positions 1, 2, 8 and 10, resulting in four mutated peptides. Each peptide was separately conjugated with either chlorogenate, carnosate, gallate, or rosmarinate given their known anti-tumor activities, creating dual targeting compounds. Molecular docking studies were conducted with the epidermal growth factor receptor (EGFR), to which the original peptide sequence is known to bind, as well as the estrogen receptor (ERα) and peroxisome proliferator-activated receptor (PPARα) using both Autodock Vina and FireDock. Based on docking results, peptide conjugates and peptides were selected and subjected to molecular dynamics simulations. MMGBSA calculations were used to further probe the binding energies. ADME studies revealed that the compounds were not CYP substrates, though most were Pgp substrates. Additionally, most of the peptides and conjugates showed MDCK permeability. Our results indicated that several of the peptide conjugates enhanced binding interactions with the receptors and resulted in stable receptor-ligand complexes; Furthermore, they may successfully target ERα and PPARα in addition to EGFR and may be further explored for synthesis and biological studies for therapeutic applications.

The Inhibitory Effect of Three Essential Oils on Candida rugosa Lipase: In Vitro and In Silico Studies

2020 ◽  
Vol 10 (3) ◽  
pp. 208-215 ◽  
Author(s):  
Talia Serseg ◽  
Khedidja Benarous ◽  
Mohamed Yousfi
Keyword(s):  
Molecular Docking ◽  
Essential Oils ◽  
In Silico ◽  
Candida Rugosa ◽  
Inhibitory Effect ◽  
Mentha Piperita ◽  
Inhibition Mechanism ◽  
Syzygium Aromaticum ◽  
In Silico Studies

Background: Essential oils have been used for centuries. EOs are gaining increasing interest because of their acceptance by consumers and their safe status. For the first time, the effect of essential oils on the inhibition of lipases has been investigated in this work. Objective: We aimed in this study to investigate in vitro the inhibitory effects of the three essential oils of most used spices: Peppermint (Mentha piperita L.), cinnamon (Cinnamomum zeylanicum L.) and Cloves (Syzygium aromaticum L. Merr. et Perry) against Candida rugose lipase. In silico studies using molecular docking have been achieved to study the inhibition mechanism of major compounds of EO: menthol, carvacrol, eugenol and cinnamylaldehyde toward CRL. Methods: The inhibitory effect of three essential oils were determined by candida rugosa enzyme and pNP-L as substrate using spectrophotometry. Autodock vina was used for molecular docking with 50 runs. Results: We have found that these essential oils have a strong inhibitory effect with IC50 values 1.09, 1.78 and 1.13 mg/ml compared with Orlistat 0.06 mg/ml. The results show competitive inhibition for the three major compounds Menthol, Carvacrol and Eugenol with uncompetitive inhibition for Cinnamaldehyde. Different repetition ratios of hydrogen bonds and hydrophobic interactions were observed. The saved interactions were with His449, Ser209, Gly123, Gly124 and Phe344 for all molecules. Conclusion: These observations support using and considering essential oils and their major compounds as good sources for design new drugs to treat candidiasis and other diseases related to Lipases.

scholarly journals Chemical Profiles and Pharmacological Properties with in Silico Studies on Elatostema papillosum Wedd

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 809 ◽  
Author(s):  
Md. Zia Uddin ◽  
Arkajyoti Paul ◽  
Ahmed Rakib ◽  
Saad Ahmed Sami ◽  
Shafi Mahmud ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Serotonin Receptor ◽  
Computational Study ◽  
Biological Activities ◽  
Binding Affinities ◽  
In Silico Studies ◽  
Cox 2 ◽  
Cox 1

The current study attempted, for the first time, to qualitatively and quantitatively determine the phytochemical components of Elatostema papillosum methanol extract and their biological activities. The present study represents an effort to correlate our previously reported biological activities with a computational study, including molecular docking, and ADME/T (absorption, distribution, metabolism, and excretion/toxicity) analyses, to identify the phytochemicals that are potentially responsible for the antioxidant, antidepressant, anxiolytic, analgesic, and anti-inflammatory activities of this plant. In the gas chromatography-mass spectroscopy analysis, a total of 24 compounds were identified, seven of which were documented as being bioactive based on their binding affinities. These seven were subjected to molecular docking studies that were correlated with the pharmacological outcomes. Additionally, the ADME/T properties of these compounds were evaluated to determine their drug-like properties and toxicity levels. The seven selected, isolated compounds displayed favorable binding affinities to potassium channels, human serotonin receptor, cyclooxygenase-1 (COX-1), COX-2, nuclear factor (NF)-κB, and human peroxiredoxin 5 receptor proteins. Phytol acetate, and terpene compounds identified in E. papillosum displayed strong predictive binding affinities towards the human serotonin receptor. Furthermore, 3-trifluoroacetoxypentadecane showed a significant binding affinity for the KcsA potassium channel. Eicosanal showed the highest predicted binding affinity towards the human peroxiredoxin 5 receptor. All of these findings support the observed in vivo antidepressant and anxiolytic effects and the in vitro antioxidant effects observed for this extract. The identified compounds from E. papillosum showed the lowest binding affinities towards COX-1, COX-2, and NF-κB receptors, which indicated the inconsequential impacts of this extract against the activities of these three proteins. Overall, E. papillosum appears to be bioactive and could represent a potential source for the development of alternative medicines; however, further analytical experiments remain necessary.

scholarly journals Evaluation of the Antioxidant, Antidiabetic, and Antiplasmodial Activities of Xanthones Isolated from Garcinia forbesii and Their In Silico Studies

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1380
Author(s):  
Johanis Wairata ◽  
Edwin Risky Sukandar ◽  
Arif Fadlan ◽  
Adi Setyo Purnomo ◽  
Muhammad Taher ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Molecular Docking ◽  
In Silico ◽  
Stem Bark ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
In Silico Studies ◽  
Dehydrogenase Enzyme ◽  
Ch2cl2 Extract

This study aimed to isolate xanthones from Garcinia forbesii and evaluated their activity in vitro and in silico. The isolated compounds were evaluated for their antioxidant activity by DPPH, ABTS and FRAP methods. The antidiabetic activity was performed against α-glucosidase and α-amylase enzymes. The antiplasmodial activity was evaluated using Plasmodium falciparum strain 3D7 sensitive to chloroquine. Molecular docking analysis on the human lysosomal acid-alpha-glucosidase enzyme (5NN8) and P. falciparum lactate dehydrogenase enzyme (1CET) and prediction of ADMET for the active compound, were also studied. For the first time, lichexanthone (1), subelliptenone H (2), 12b-hydroxy-des-D-garcigerrin A (3), garciniaxanthone B (4) and garcigerin A (5) were isolated from the CH2Cl2 extract of the stem bark of G. forbesii. Four xanthones (Compounds 2–5) showed strong antioxidant activity. In vitro α-glucosidase test showed that Compounds 2 and 5 were more active than the others, while Compound 4 was the strongest against α-amylase enzymes. In vitro antiplasmodial evaluation revealed that Compounds 2 and 3 showed inhibitory activity on P. falciparum. Molecular docking studies confirmed in vitro activity. ADMET predictions suggested that Compounds 1–5 were potential candidates for oral drugs. The isolated 2–5 can be used as promising phytotherapy in antidiabetic and antiplasmodial treatment.

scholarly journals In-vitro anti-diabetic activity and in-silico studies of binding energies of palmatine with alpha-amylase, alpha-glucosidase and DPP-IV enzymes

Pharmacia ◽  
2020 ◽  
Vol 67 (4) ◽  
pp. 363-371
Author(s):  
Patrick Okechukwu ◽  
Mridula Sharma ◽  
Wen Hui Tan ◽  
Hor Kuan Chan ◽  
Kavita Chirara ◽  
...  
Keyword(s):  
In Silico ◽  
Binding Energies ◽  
Alpha Amylase ◽  
Binding Interactions ◽  
Inhibiting Effect ◽  
Dpp Iv ◽  
In Silico Studies ◽  
Significant Difference ◽  
Alpha Glucosidase

Palmatine a protoberberine alkaloid has been previously reported to possess in vivo antidiabetic and antioxidant property. The aim of the experiment is to evaluate the in vitro antidiabetic activity and in-silico studies of the binding energies of Palmatine, acarbose, and Sitagliptin with the three enzymes of alpha-amylase, alpha-glucosidase, and dipeptidyl peptidase-IV (DPP-IV). The in vitro antidiabetic study was done by evaluating the inhibitory effect of palmatine on the activities of alpha-amylase, alpha-glucosidase, and DPP-IV. Acarbose, and sitagliptin was used as standard drug. The molecular docking study was performed to study the binding interactions of palmatine with alpha-glucosidase, a-amylase, and DPP-IV. The binding interactions were compared with the standard compounds Sitagliptin and acarbose. Palmatine with IC50 (1.31 ± 0.27 µM) showed significant difference of (&lt; 0.0001) higher inhibiting effect on alpha-amylase and weak inhibiting effect on alpha-glucosidase enzyme with IC50 (9.39 ± 0.27 µM) and DPP-IV with IC50 (8.7 ± 1.82 µM). Palmatine possess inhibition effect on the three enzymes.

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