In silico studies on the therapeutic potential of novel marker compounds isolated from chemically modified bioactive fraction from Curcuma longa (Non-carbonyl Curcuma longa)

: Cannabidiol (CBD) is a non-psychotropic phytocannabinoid which represents one of the constituents of the “phytocomplex” of Cannabis sativa. This natural compound is attracting growing interest since when CBD-based remedies and commercial products were marketed. This review aims to exhaustively address the extractive and analytical approaches that have been developed for the isolation and quantification of CBD. Recent updates on cutting-edge technologies were critically examined in terms of yield, sensitivity, flexibility and performances in general, and are reviewed alongside original representative results. As an add-on to currently available contributions in the literature, the evolution of the novel, efficient synthetic approaches for the preparation of CBD, a procedure which is appealing for the pharmaceutical industry, is also discussed. Moreover, with the increasing interest on the therapeutic potential of CBD and the limited understanding of the undergoing biochemical pathways, the reader will be updated about recent in silico studies on the molecular interactions of CBD towards several different targets attempting to fill this gap. Computational data retrieved from the literature have been integrated with novel in silico experiments, critically discussed to provide a comprehensive and updated overview on the undebatable potential of CBD and its therapeutic profile.

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Cytotoxicity, Antimicrobial, and In Silico Studies of Secondary Metabolites From Aspergillus sp. Isolated From Tecoma stans (L.) Juss. Ex Kunth Leaves

Frontiers in Chemistry ◽

10.3389/fchem.2021.760083 ◽

2021 ◽

Vol 9 ◽

Author(s):

Heba E. Elsayed ◽

Reem A. Kamel ◽

Reham R. Ibrahim ◽

Ahmed S. Abdel-Razek ◽

Mohamed A. Shaaban ◽

...

Keyword(s):

Secondary Metabolites ◽

In Silico ◽

Therapeutic Potential ◽

Antibacterial Activities ◽

Antimicrobial Activities ◽

Kinase Domain ◽

Binding Score ◽

In Silico Studies ◽

Binding Cleft ◽

Aspergillus Sp

Endophytes are prolific producers of privileged secondary metabolites with diverse therapeutic potential, although their anticancer and antimicrobial potential still have a room for further investigation. Herein, seven known secondary metabolites namely, arugosin C (1), ergosterol (2), iso-emericellin (3), sterigmatocystin (4), dihydrosterigmatocystin (5), versicolorin B (6), and diorcinol (7) were isolated from the rice culture of Aspergillus sp. retrieved from Tecoma stans (L.) Juss. ex Kunth leaves. Their anticancer and antimicrobial activities were evaluated in MTT and agar well diffusion assays, respectively. The cytotoxicity results showed that metabolite 3 displayed the best viability inhibition on the MCF-7 breast cancer cells with IC50 = 225.21 µM, while 5 on the HepG2 hepatocellular carcinoma cells with IC50 = 161.81 µM. 5 demonstrated a 60% apoptotic mode of cell death which is virtually correlated to its high docking affinity to Hsp90 ATP binding cleft (binding score −8.4 Kcal/mol). On the other side, metabolites 4 and 5 displayed promising antimicrobial activity especially on Pseudomonas aeruginosa with MIC = 125 μg/ml. The observed effect may be likely related to their excellent in silico inhibition of the bacterial DNA-gyrase kinase domain (binding score −10.28 Kcal/mol). To the best of our knowledge, this study is the first to report the promising cytotoxic and antibacterial activities of metabolites 3, 4, and 5 which needs further investigation and renovation to therapeutic leads.

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Activity of phytochemical constituents of Curcuma longa (turmeric) and Andrographis paniculata against coronavirus (COVID-19): an in silico approach

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-020-00126-x ◽

2020 ◽

Vol 6 (1) ◽

Cited By ~ 2

Author(s):

Kalirajan Rajagopal ◽

Potlapati Varakumar ◽

Aparma Baliwada ◽

Gowramma Byran

Keyword(s):

Active Site ◽

In Silico ◽

Chemical Constituents ◽

Curcuma Longa ◽

Andrographis Paniculata ◽

Significant Activity ◽

Binding Modes ◽

Main Protease ◽

In Silico Admet ◽

In Silico Studies

Abstract Background In early 2020, many scientists are rushing to discover novel drugs and vaccines against the coronavirus, and treatments for COVID-19, because coronavirus disease 2019 (COVID-19), a life-threatening viral disease, affected first in China and quickly spread throughout the world. In this article, in silico studies have been performed to explore the binding modes of chemical constituents for natural remedies like Curcuma longa (turmeric) and Andrographis paniculata against COVID-19 (PDB ID 5R82) targeting coronavirus using Schrodinger suit 2019-4. The molecular docking studies are performed by the Glide module, in silico ADMET screening was performed by the QikProp module, and binding energy of ligands was calculated using the Prime MM-GB/SA module. Results The chemical constituents from turmeric like cyclocurcumin and curcumin and from Andrographis paniculata like andrographolide and dihydroxy dimethoxy flavone are significantly binding with the active site of SARS CoV-2 main protease with Glide score more than − 6 when compared to the currently used drugs hydroxychloroquine (− 5.47) and nelfinavir (− 5.93). When compared to remdesivir (− 6.38), cyclocurcumin from turmeric is significantly more active. The docking results of the compounds exhibited similar mode of interactions with SARS CoV-2. Main protease and the residues THR24, THR25, THR26, LEU27, SER46, MET49, HIE41, GLN189, ARG188, ASP187, MET165, HIE164, PHE181, and THR54 play a crucial role in binding with ligands. Conclusion Based on in silico investigations, the chemical constituents from turmeric like cyclocurcumin and curcumin and from Andrographis paniculata like andrographolide and dihydroxy dimethoxy flavone, significantly binding with the active site of SARS CoV-2 main protease, may produce significant activity and be useful for further development.

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Phytocompounds of Curcuma longa extract are more effective against bacterial biofilm than pure curcumin only: An in-vitro and in-silico analysis

Kuwait Journal of Science ◽

10.48129/kjs.v48i2.8310 ◽

2021 ◽

Vol 48 (2) ◽

Author(s):

Dibyajit Lahiri ◽

◽

Moupriya Nag ◽

Soumik Dey ◽

Bandita Dutta ◽

...

Keyword(s):

Bioactive Compounds ◽

In Silico ◽

Methyl Palmitate ◽

Curcuma Longa ◽

Research Work ◽

Bioactive Compound ◽

Bacterial Biofilm ◽

Antibiofilm Activity ◽

Electron Microscopic ◽

In Silico Studies

Bioactive compounds are the group of secondary metabolites of plants that have a potent impact on antimicrobial and antibiofilm agents. Although Curcuma longa (turmeric) is well known for its antimicrobial activity, the question arises if curcumin, the primary bioactive compound is only responsible for it or the synergistic and simultaneous contribution of more than one bioactive compound are responsible for this antibiofilm efficacy. The research work aims to determine the efficacy of the extract Curcuma longa has a higher potential of antimicrobial and antibiofilm activity than the purchased curcumin and standard antibiotic. Present work was initiated with GC-MS analysis of the ethanolic extract of Curcuma longa (turmeric) and showed that in addition to curcumin, methyl palmitate de-hydro zingerone had a higher percent of availability within the extract. The in-silico studies also showed that when targeted upon Gram-positive biofilm-forming protein of Staphylococcus aureus (3TIP), curcumin alone had a binding constant value of -6.33 Kcal/mol but showed a value of -17.811 Kcal/mol when acted in association with Dehydrozingerone. Similarly, the binding constant's value changed from -6.07 Kcal/mol to - 23.844 Kcal/mol, when Gram-negative biofilm-forming protein (3ZYB) of Pseudomonas aeruginosa was acted upon by curcumin only and in association with methyl palmitate, respectively. Lower minimum inhibitory concentration (MIC) and higher effectivity in reducing the bacterial quorum sensing (QS) activity of the turmeric extract than pure Curcumin indicated the higher antimicrobial and antibiofilm efficiency of the extract, respectively. This indicated clearly that the synergistic action of all the bioactive compounds imparts the antibiofilm activity of turmeric. The result was further confirmed by the scanning electron microscopic (SEM) studies, fluorescent microscopic studies, and FTIR analysis of EPS as well.

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Design and In silico Studies of 2,5-Disubstituted 1,2,4-Triazole and 1,3,4-Thiadiazole Derivatives as Pteridine Reductase 1 Inhibitors

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i29a31575 ◽

2021 ◽

pp. 166-178

Author(s):

Shraddha Phadke ◽

Devender Pathak ◽

Rakesh Somani

Keyword(s):

In Silico ◽

Therapeutic Potential ◽

Structural Features ◽

Lipinski’S Rule ◽

Drug Mechanism ◽

In Silico Studies ◽

Lipinski’S Rule Of Five ◽

Thiadiazole Derivatives

Aims: Design and in silico studies of 2,5-disubstituted triazole and thiadiazole derivatives as Pteridine Reductase 1 inhibitors. With a view to develop effective agents against Leishmaniasis, 2-substituted-5-[(1H-benzimidazol-2yl) methyl] azole derivatives (A1-A12) were designed against the target enzyme Pteridine reductase 1. Methodology: The series was designed by targeting Pteridine reductase 1 which is an enzyme responsible for folate and pterin metabolism. Based on thorough study of the enzyme structure and structural features of ligands required for optimum interaction with the enzyme, a series of 12 compounds consisting of 2,5-disubstituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives was designed. In silico studies were carried out which included docking studies (using V Life software) to understand binding of the compounds with enzyme PTR1, ADMET studies, drug likeness studies for physicochemical properties and bioactivity studies to understand the possible mechanism of action of the compounds. These studies were undertaken using online softwares, molinspiration and admetSAR web servers. Results: Compounds A10 and A12 gave the best docking scores of -59.9765 and -60.4373 respectively that were close to dihydrobiopterin (original substrate). All the compounds complied with Lipinski’s rule of five. Most of the compounds displayed favorable ADMET properties. Conclusion: The 2,5-disubstituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives exhibited good binding affinity for PTR1 enzyme (PDB code: 1E92). The docking scores indicated that enzyme binding may be governed by the nature and size of the substituents on the azole ring. The compounds display well-defined drug-like and pharmacokinetic properties based on Lipinski’s rule of five with additional physicochemical and ADMET parameters. Bioactivity studies suggested the possible drug mechanism as enzyme inhibition. Hence, this study provides evidence for consideration of valuable ligands in 2,5-disubstituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives as potential pteridine reductase 1 inhibitor and further in vitro and in vivo investigations may prove its therapeutic potential.

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Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review

International Journal of Molecular Sciences ◽

10.3390/ijms222011069 ◽

2021 ◽

Vol 22 (20) ◽

pp. 11069

Author(s):

Ridhima Kaul ◽

Pradipta Paul ◽

Sanjay Kumar ◽

Dietrich Büsselberg ◽

Vivek Dhar Dwivedi ◽

...

Keyword(s):

Therapeutic Intervention ◽

Clinical Studies ◽

In Silico ◽

Therapeutic Potential ◽

Health Concern ◽

N Protein ◽

Synthetic Drugs ◽

In Silico Studies

The ongoing COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a globally leading public health concern over the past two years. Despite the development and administration of multiple vaccines, the mutation of newer strains and challenges to universal immunity has shifted the focus to the lack of efficacious drugs for therapeutic intervention for the disease. As with SARS-CoV, MERS-CoV, and other non-respiratory viruses, flavonoids present themselves as a promising therapeutic intervention given their success in silico, in vitro, in vivo, and more recently, in clinical studies. This review focuses on data from in vitro studies analyzing the effects of flavonoids on various key SARS-CoV-2 targets and presents an analysis of the structure-activity relationships for the same. From 27 primary papers, over 69 flavonoids were investigated for their activities against various SARS-CoV-2 targets, ranging from the promising 3C-like protease (3CLpro) to the less explored nucleocapsid (N) protein; the most promising were quercetin and myricetin derivatives, baicalein, baicalin, EGCG, and tannic acid. We further review promising in silico studies featuring activities of flavonoids against SARS-CoV-2 and list ongoing clinical studies involving the therapeutic potential of flavonoid-rich extracts in combination with synthetic drugs or other polyphenols and suggest prospects for the future of flavonoids against SARS-CoV-2.

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Cheonggukjang-Specific Component 1,3-Diphenyl-2-propanone as A Novel PPARα/γ Dual Agonist: An In Vitro and In Silico Study

International Journal of Molecular Sciences ◽

10.3390/ijms221910884 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10884

Author(s):

Radha Arulkumar ◽

Hee-Jin Jung ◽

Sang-Gyun Noh ◽

Daeui Park ◽

Hae-Young Chung

Keyword(s):

In Silico ◽

Dietary Intervention ◽

Therapeutic Potential ◽

Biological Activities ◽

Fermented Soybean ◽

Soybean Paste ◽

In Silico Studies ◽

Dual Agonist ◽

In Silico Tools

Background: Cheonggukjang is a traditional fermented soybean paste that is mostly consumed in Korea. However, the biological activities of Cheonggukjang specific compounds have not been studied. Thus, we aimed to discover a novel dual agonist for PPARα/γ from dietary sources such as Cheonggukjang specific volatile compounds and explore the potential role of PPARα/γ dual agonists using in vitro and in silico tools. Methods: A total of 35 compounds were selected from non-fermented and fermented soybean products cultured with Bacillus subtilis, namely Cheonggukjang, for analysis by in vitro and in silico studies. Results: Molecular docking results showed that 1,3-diphenyl-2-propanone (DPP) had the lowest docking score for activating PPARα (1K7L) and PPARγ (3DZY) with non-toxic effects. Moreover, DPP significantly increased the transcriptional activities of both PPARα and PPARγ and highly activated its expression in Ac2F liver cells, in vitro. Here, we demonstrated for the first time that DPP can act as a dual agonist of PPARα/γ using in vitro and in silico tools. Conclusions: The Cheonggukjang-specific compound DPP could be a novel PPARα/γ dual agonist and it is warranted to determine the therapeutic potential of PPARα/γ activation by dietary intervention and/or supplementation in the treatment of metabolic disorders without causing any adverse effects.

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Activity of Some Novel Chalcone Substituted 9-anilinoacridines against Coronavirus (COVID-19): A Computational Approach

Coronaviruses ◽

10.2174/2666796701999200625210746 ◽

2020 ◽

Vol 1 (1) ◽

pp. 13-22

Author(s):

Rajagopal Kalirajan

Keyword(s):

Molecular Docking ◽

In Silico ◽

Therapeutic Potential ◽

Viral Disease ◽

Docking Studies ◽

Molecular Docking Studies ◽

Novel Drugs ◽

In Silico Studies ◽

Life Threatening ◽

Similar Mode

Background: In the year earlier part of 2020, many scientists urged to discover novel drugs against for the treatments of COVID-19. Coronavirus Disease 2019 (COVID-19), a life-threatening viral disease, was discovered first in China and quickly spread throughout the world. Objective: In the present article, some novel chalcone substituted 9-anilinoacridines (1a-z) were developed by in silico studies for their COVID19 inhibitory activity. Molecular docking studies of the ligands 1a-z were performed against COVID19 (PDB id - 5R82) targeting the coronavirus using Schrodinger suite 2019-4. Methods: The molecular docking studies were performed by the Glide module and the binding energy of ligands was calculated using the PRIME MM-GB/SA module of Schrodinger suite 2019-4. Results: From the results, many compounds are significantly active against COVID19 with a Glide score of more than -5.6 when compared to the currently used drug for the treatment of COVID19, Hydroxychloroquine (-5.47). The docking results of the compounds exhibited similar mode of interactions with COVID19 and the residues, THR25, THR26, LEU27, SER46, MET49, HIE41, GLN189, ARG188, ASP187, VAL186, HIE164, ASN142, and GLY143 play a crucial role in binding with ligands. MMGBSA binding calculations of the most potent inhibitors are more stably favourable. Conclusion: From the results of in-silico studies, it provides strong evidence for the consideration of valuable ligands in chalcone substituted 9-anilinoacridines as potential COVID19 inhibitors and the compounds, 1x,a,r,s with significant Glide scores may produce significant COVID19 activity for further development, which may prove their therapeutic potential.

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Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

Current Pharmaceutical Design ◽

10.2174/1381612826666201112143230 ◽

2020 ◽

Vol 26 ◽

Author(s):

John Chen ◽

Andrew Martin ◽

Warren H. Finlay

Keyword(s):

Drug Delivery ◽

In Silico ◽

Local Drug Delivery ◽

In Vivo Studies ◽

Intranasal Drug Delivery ◽

Nasal Sprays ◽

In Silico Studies ◽

Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

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