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13 pages, 3965 KiB

Open AccessArticle

In Silico Identification of Natural Product-Based Inhibitors Targeting IL-1β/IL-1R Protein–Protein Interface

by Ting-ting Liu, Yan-kun Chen, Muhammad Adil, Mazen Almehmadi, Fahad M. Alshabrmi, Mamdouh Allahyani, Ahad Amer Alsaiari, Pei Liu, Muhammad Raheel Khan and Qinghua Peng

Molecules 2023, 28(13), 4885; https://doi.org/10.3390/molecules28134885 - 21 Jun 2023

Cited by 1 | Viewed by 1438

Abstract

IL-1β mediates inflammation and regulates immune responses, cell proliferation, and differentiation. Dysregulation of IL-1β is linked to inflammatory and autoimmune diseases. Elevated IL-1β levels are found in patients with severe COVID-19, indicating its excessive production may worsen the disease. Also, dry eye disease [...] Read more.

IL-1β mediates inflammation and regulates immune responses, cell proliferation, and differentiation. Dysregulation of IL-1β is linked to inflammatory and autoimmune diseases. Elevated IL-1β levels are found in patients with severe COVID-19, indicating its excessive production may worsen the disease. Also, dry eye disease patients show high IL-1β levels in tears and conjunctival epithelium. Therefore, IL-1β signaling is a potential therapeutic targeting for COVID-19 and aforementioned diseases. No small-molecule IL-1β inhibitor is clinically approved despite efforts. Developing such inhibitors is highly desirable. Herein, a docking-based strategy was used to screen the TCM (Traditional Chinese Medicine) database to identify possible IL-1β inhibitors with desirable pharmacological characteristics by targeting the IL-1β/IL-1R interface. Primarily, the docking-based screening was performed by selecting the crucial residues of IL-1β interface to retrieve the potential compounds. Afterwards, the compounds were shortlisted on the basis of binding scores and significant interactions with the crucial residues of IL-1β. Further, to gain insights into the dynamic behavior of the protein–ligand interactions, MD simulations were performed. The analysis suggests that four selected compounds were stabilized in an IL-1β pocket, possibly blocking the formation of an IL-1β/IL-1R complex. This indicates their potential to interfere with the immune response, making them potential therapeutic agents to investigate further. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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17 pages, 4668 KiB

Open AccessArticle

Docking-Based Evidence for the Potential of ImmunoDefender: A Novel Formulated Essential Oil Blend Incorporating Synergistic Antiviral Bioactive Compounds as Promising Mpro Inhibitors against SARS-CoV-2

by Ayoub Ksouri, Anis Klouz, Balkiss Bouhaouala-Zahar, Fathi Moussa and Mounir Bezzarga

Molecules 2023, 28(11), 4296; https://doi.org/10.3390/molecules28114296 - 24 May 2023

Cited by 1 | Viewed by 1851

Abstract

Essential oils (Eos) have demonstrated antiviral activity, but their toxicity can hinder their use as therapeutic agents. Recently, some essential oil components have been used within safe levels of acceptable daily intake limits without causing toxicity. The “ImmunoDefender,” a novel antiviral compound made [...] Read more.

Essential oils (Eos) have demonstrated antiviral activity, but their toxicity can hinder their use as therapeutic agents. Recently, some essential oil components have been used within safe levels of acceptable daily intake limits without causing toxicity. The “ImmunoDefender,” a novel antiviral compound made from a well-known mixture of essential oils, is considered highly effective in treating SARS-CoV-2 infections. The components and doses were chosen based on existing information about their structure and toxicity. Blocking the main protease (Mpro) of SARS-CoV-2 with high affinity and capacity is critical for inhibiting the virus’s pathogenesis and transmission. In silico studies were conducted to examine the molecular interactions between the main essential oil components in “ImmunoDefender” and SARS-CoV-2 Mpro. The screening results showed that six key components of ImmunoDefender formed stable complexes with Mpro via its active catalytic site with binding energies ranging from −8.75 to −10.30 kcal/mol, respectively for Cinnamtannin B1, Cinnamtannin B2, Pavetannin C1, Syzyginin B, Procyanidin C1, and Tenuifolin. Furthermore, three essential oil bioactive inhibitors, Cinnamtannin B1, Cinnamtannin B2, and Pavetannin C, had significant ability to bind to the allosteric site of the main protease with binding energies of −11.12, −10.74, and −10.79 kcal/mol; these results suggest that these essential oil bioactive compounds may play a role in preventing the attachment of the translated polyprotein to Mpro, inhibiting the virus’s pathogenesis and transmission. These components also had drug-like characteristics similar to approved and effective drugs, suggesting that further pre-clinical and clinical studies are needed to confirm the generated in silico outcomes. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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15 pages, 5984 KiB

Open AccessArticle

Virtual Screening of a Library of Naturally Occurring Anthraquinones for Potential Anti-Fouling Agents

by Gagan Preet, Rishi Vachaspathy Astakala, Jessica Gomez-Banderas, Joy Ebenezer Rajakulendran, Ahlam Haj Hasan, Rainer Ebel and Marcel Jaspars

Molecules 2023, 28(3), 995; https://doi.org/10.3390/molecules28030995 - 19 Jan 2023

Cited by 2 | Viewed by 2356

Abstract

Marine biofouling is the undesired accumulation of organic molecules, microorganisms, macroalgae, marine invertebrates, and their by-products on submerged surfaces. It is a serious challenge for marine vessels and the oil, gas, and renewable energy industries, as biofouling can cause economic losses for these [...] Read more.

Marine biofouling is the undesired accumulation of organic molecules, microorganisms, macroalgae, marine invertebrates, and their by-products on submerged surfaces. It is a serious challenge for marine vessels and the oil, gas, and renewable energy industries, as biofouling can cause economic losses for these industries. Natural products have been an abundant source of therapeutics since the start of civilisation. Their use as novel anti-fouling agents is a promising approach for replacing currently used, harmful anti-fouling agents. Anthraquinones (AQs) have been used for centuries in the food, pharmaceutical, cosmetics, and paint industries. Citreorosein and emodin are typical additives used in the anti-fouling paint industry to help improve the global problem of biofouling. This study is based on our previous study, in which we presented the promising activity of structurally related anthraquinone compounds against biofilm-forming marine bacteria. To help uncover the anti-fouling potential of other AQ-related structures, 2194 compounds from the COCONUT natural products database were analysed. Molecular docking analysis was performed to assess the binding strength of these compounds to the LuxP protein in Vibrio carchariae. The LuxP protein is a vital binding protein responsible for the movements of autoinducers within the quorum sensing system; hence, interrupting the process at an early stage could be an effective strategy. Seventy-six AQ structures were found to be highly docked, and eight of these structures were used in structure-based pharmacophore modelling, resulting in six unique pharmacophore features. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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18 pages, 4925 KiB

Open AccessArticle

Three New Acrylic Acid Derivatives from Achillea mellifolium as Potential Inhibitors of Urease from Jack Bean and α-Glucosidase from Saccharomyces cerevisiae

by Umar Farooq, Sara Khan, Sadia Naz, Tanveer A. Wani, Syed Majid Bukhari, Abullahi Tunde Aborode, Sohail Anjum Shahzad and Seema Zargar

Molecules 2022, 27(15), 5004; https://doi.org/10.3390/molecules27155004 - 06 Aug 2022

Cited by 2 | Viewed by 1462

Abstract

(1) Background: Achillea mellifolium belongs to a highly reputed family of medicinal plants, with plant extract being used as medicine in indigenous system. However, limited data is available regarding the exploitation of the medicinal potential of isolated pure compounds from this family; (2) [...] Read more.

(1) Background: Achillea mellifolium belongs to a highly reputed family of medicinal plants, with plant extract being used as medicine in indigenous system. However, limited data is available regarding the exploitation of the medicinal potential of isolated pure compounds from this family; (2) Methods: A whole plant extract was partitioned into fractions and on the basis of biological activity, an ethyl acetate fraction was selected for isolation of pure compounds. Isolated compounds were characterized using different spectroscopic techniques. The compounds isolated from this study were tested for their medicinal potential using in-vitro enzyme assay, coupled with in-silico studies; (3) Results: Three new acrylic acid derivatives (1–3) have been isolated from the ethyl acetate fraction of Achillea mellifolium. The characterization of these compounds (1–3) was carried out using UV/Vis, FT-IR, 1D and 2D-NMR spectroscopy (¹H-NMR, ¹³C-NMR, HMBC, NOESY) and mass spectrometry. These acrylic acid derivatives were further evaluated for their enzyme inhibition potential against urease from jack bean and α glucosidase from Saccharomyces cerevisiae, using both in-silico and in-vitro approaches. In-vitro studies showed that compound 3 has the highest inhibition against urease enzyme (IC₅₀ =10.46 ± 0.03 μΜ), followed by compound 1 and compound 2 with percent inhibition and IC₅₀ value of 16.87 ± 0.02 c and 13.71 ± 0.07 μΜ, respectively, compared to the standard (thiourea-IC₅₀ = 21.5 ± 0.01 μΜ). The investigated IC₅₀ value of compound 3 against the urease enzyme is two times lower compared to thiourea, suggesting that this compound is twice as active compared to the standard drug. On the other hand, all three compounds (1–3) revealed mild inhibition potential against α-glucosidase. In-silico molecular docking studies, in combination with MD simulations and free energy, calculations were also performed to rationalize their time evolved mode of interaction inside the active pocket. Binding energies were computed using a MMPBSA approach, and the role of individual residues to overall binding of the inhibitors inside the active pockets were also computed; (4) Conclusions: Together, these studies confirm the inhibitory potential of isolated acrylic acid derivatives against both urease and α-glucosidase enzymes; however, their inhibition potential is better for urease enzyme even when compared to the standard. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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35 pages, 15537 KiB

Open AccessArticle

Solanaceae Family Phytochemicals as Inhibitors of 3C-Like Protease of SARS-CoV-2: An In Silico Analysis

by Raisul Awal Mahmood, Anamul Hasan, Mohammed Rahmatullah, Alok K. Paul, Rownak Jahan, Khoshnur Jannat, Tohmina Afroze Bondhon, Tooba Mahboob, Veeranoot Nissapatorn, Maria de Lourdes Pereira, Tridib K. Paul, Ommay Hany Rumi, Christophe Wiart and Polrat Wilairatana

Molecules 2022, 27(15), 4739; https://doi.org/10.3390/molecules27154739 - 25 Jul 2022

Cited by 3 | Viewed by 2030

Abstract

COVID-19, caused by the coronavirus SARS-CoV-2, emerged in late December 2019 in Wuhan, China. As of 8 April 2022, the virus has caused a global pandemic, resulting in 494,587,638 infections leading to 6,170,283 deaths around the world. Although several vaccines have received emergency [...] Read more.

COVID-19, caused by the coronavirus SARS-CoV-2, emerged in late December 2019 in Wuhan, China. As of 8 April 2022, the virus has caused a global pandemic, resulting in 494,587,638 infections leading to 6,170,283 deaths around the world. Although several vaccines have received emergency authorization from USA and UK drug authorities and two more in Russia and China, it is too early to comment on the prolonged effectiveness of the vaccines, their availability, and affordability for the developing countries of the world, and the daunting task to vaccinate 7 billion people of the world with two doses of the vaccine with additional booster doses. As a result, it is still worthwhile to search for drugs and several promising leads have been found, mainly through in silico studies. In this study, we have examined the binding energies of several alkaloids and anthocyanin derivatives from the Solanaceae family, a family which contains common consumable vegetables and fruit items such as eggplant, pepper, and tomatoes. Our study demonstrates that Solanaceae family alkaloids such as incanumine and solaradixine, as well as anthocyanins and anthocyanidins, have very high predicted binding energies for the 3C-like protease of SARS-CoV-2 (also known as Mpro). Since Mpro is vital for SARS-CoV-2 replication, the compounds merit potential for further antiviral research towards the objective of obtaining affordable drugs. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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12 pages, 10173 KiB

Open AccessArticle

Unrevealing the Potential of Sansevieria trifasciata Prain Fraction for the Treatment of Androgenetic Alopecia by Inhibiting Androgen Receptors Based on LC-MS/MS Analysis, and In-Silico Studies

by Henny Kasmawati, Resmi Mustarichie, Eli Halimah, Ruslin Ruslin, Arfan Arfan and Nurramadhani A. Sida

Molecules 2022, 27(14), 4358; https://doi.org/10.3390/molecules27144358 - 07 Jul 2022

Cited by 7 | Viewed by 2300

Abstract

Androgenetic Alopecia (AGA) occurs due to over-response to androgens causing severe hair loss on the scalp, and requires the development of new and efficient drugs to treat this condition. This study explores and identifies secondary metabolites from Sansevieriatrifasciata Prain using the LC-MS/MS [...] Read more.

Androgenetic Alopecia (AGA) occurs due to over-response to androgens causing severe hair loss on the scalp, and requires the development of new and efficient drugs to treat this condition. This study explores and identifies secondary metabolites from Sansevieriatrifasciata Prain using the LC-MS/MS and in-silico method. The inhibitory activity of bioactive compounds from S. trifasciata Prain against androgen receptors (PDB ID: 4K7A) was evaluated molecularly using docking and dynamics studies by comparing their binding energies, interactions, and stability with minoxidil. The results of the LC-MS/MS analysis identified Methyl pyrophaeophorbide A (1), Oliveramine (2), (2S)-3′, 4′-Methylenedioxy-5, 7-dimethoxyflavane (3), 1-Acetyl-β-carboline (4), Digiprolactone (5), Trichosanic acid (6) and Methyl gallate (7) from the leaves subfraction of this plant. Three alkaloid compounds (compounds 1, 3, and 4), and one flavonoid (compound 2), had lower docking scores of −7.0, −5.8, −5.2, and −6.3 kcal/mol, respectively. The prediction of binding energy using the MM-PBSA approach ensured that the potency of the four compounds was better than minoxidil, with energies of −66.13, −59.36, −40.39, and −40.25 kJ/mol for compounds 1, 3, 2, and 4, respectively. The dynamics simulation shows the stability of compound 1 based on the trajectory analysis for the 100 ns simulation. This research succeeded in identifying the compound and assessing the anti-alopecia activity of Sansevieria trifasciata Prain. Seven compounds were identified as new compounds never reported in Sansevieria trifasciata Prain. Four compounds were predicted to have better anti-alopecia activity than minoxidil in inhibiting androgen receptors through an in silico approach. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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12 pages, 3251 KiB

Open AccessArticle

Antiviral Efficacy of Selected Natural Phytochemicals against SARS-CoV-2 Spike Glycoprotein Using Structure-Based Drug Designing

by Bandar Hamad Aloufi, Mejdi Snoussi and Abdel Moneim E. Sulieman

Molecules 2022, 27(8), 2401; https://doi.org/10.3390/molecules27082401 - 08 Apr 2022

Cited by 4 | Viewed by 2214

Abstract

SARS-CoV-2 is a highly virulent coronavirus that first surfaced in late 2019 and has since created a pandemic of the acute respiratory sickness known as “coronavirus disease 2019” (COVID-19), posing a threat to human health and public safety. S-RBD is a coronaviral protein [...] Read more.

SARS-CoV-2 is a highly virulent coronavirus that first surfaced in late 2019 and has since created a pandemic of the acute respiratory sickness known as “coronavirus disease 2019” (COVID-19), posing a threat to human health and public safety. S-RBD is a coronaviral protein that is essential for a coronavirus (CoV) to bind and penetrate into host cells. As a result, it has become a popular pharmacological target. The goal of this study was to find potential candidates for anti-coronavirus disease 2019 (COVID-19) drugs by targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-RBD with novel bioactive compounds and molecular interaction studies of 15,000 phytochemicals belonging to different flavonoid subgroups. A spike protein crystal structure attached to the ACE2 structure was obtained from the PDB database. A library of 15,000 phytochemicals was made by collecting compounds from different databases, such as the Zinc-database, PubChem-database, and MPD3-database. This library was docked against a receptor binding domain of a spike glycoprotein through the Molecular Operating Environment (MOE). The top drug candidates Phylloflavan, Milk thistle, Ilexin B and Isosilybin B, after virtual screening, were selected on the basis of the least binding score. Phylloflavan ranked as the top compound because of its least binding affinity score of −14.09 kcal/mol. In silico studies showed that all those compounds showed good activity and could be used as an immunological response with no bioavailability issues. Absorption, distribution, metabolism, excretion and a toxicological analysis were conducted through SwissADME. Stability and effectiveness of the docked complexes were elucidated by performing the 100 ns molecular dynamic simulation through the Desmond package. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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26 pages, 4602 KiB

Open AccessArticle

Phytochemical and In Silico ADME/Tox Analysis of Eruca sativa Extract with Antioxidant, Antibacterial and Anticancer Potential against Caco-2 and HCT-116 Colorectal Carcinoma Cell Lines

by Amir Mahgoub Awadelkareem, Eyad Al-Shammari, Abd Elmoneim O. Elkhalifa, Mohd Adnan, Arif Jamal Siddiqui, Mejdi Snoussi, Mohammad Idreesh Khan, Z R Azaz Ahmad Azad, Mitesh Patel and Syed Amir Ashraf

Molecules 2022, 27(4), 1409; https://doi.org/10.3390/molecules27041409 - 19 Feb 2022

Cited by 27 | Viewed by 3507

Abstract

Eruca sativa Mill. (E. sativa) leaves recently grabbed the attention of scientific communities around the world due to its potent bioactivity. Therefore, the present study investigates the metabolite profiling of the ethanolic crude extract of E. sativa leaves using high resolution-liquid [...] Read more.

Eruca sativa Mill. (E. sativa) leaves recently grabbed the attention of scientific communities around the world due to its potent bioactivity. Therefore, the present study investigates the metabolite profiling of the ethanolic crude extract of E. sativa leaves using high resolution-liquid chromatography-mass spectrometry (HR-LC/MS), including antibacterial, antioxidant and anticancer potential against human colorectal carcinoma cell lines. In addition, computer-aided analysis was performed for determining the pharmacokinetic properties and toxicity prediction of the identified compounds. Our results show that E. sativa contains several bioactive compounds, such as vitamins, fatty acids, alkaloids, flavonoids, terpenoids and phenols. Furthermore, the antibacterial assay of E. sativa extract showed inhibitory effects of the tested pathogenic bacterial strains. Moreover, the antioxidant activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H₂O₂) were found to be IC₅₀ = 66.16 μg/mL and 76.05 μg/mL, respectively. E. sativa also showed promising anticancer activity against both the colorectal cancer cells HCT-116 (IC₅₀ = 64.91 μg/mL) and Caco-2 (IC₅₀ = 83.98 μg/mL) in a dose/time dependent manner. The phytoconstituents identified showed promising pharmacokinetics properties, representing a valuable source for drug or nutraceutical development. These investigations will lead to the further exploration as well as development of E. sativa-based nutraceutical products. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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14 pages, 3387 KiB

Open AccessArticle

Computational Simulations Highlight the IL2Rα Binding Potential of Polyphenol Stilbenes from Fenugreek

by Apoorva M. Kulkarni, Shraddha Parate, Gihwan Lee, Yongseong Kim, Tae Sung Jung, Keun Woo Lee and Min Woo Ha

Molecules 2022, 27(4), 1215; https://doi.org/10.3390/molecules27041215 - 11 Feb 2022

Cited by 3 | Viewed by 2010

Abstract

Widely used in global households, fenugreek is well known for its culinary and medicinal uses. The various reported medicinal properties of fenugreek are by virtue of the different natural phytochemicals present in it. Regarded as a promising target, interleukin 2 receptor subunit alpha [...] Read more.

Widely used in global households, fenugreek is well known for its culinary and medicinal uses. The various reported medicinal properties of fenugreek are by virtue of the different natural phytochemicals present in it. Regarded as a promising target, interleukin 2 receptor subunit alpha (IL2Rα) has been shown to influence immune responses. In the present research, using in silico techniques, we have demonstrated the potential IL2Rα binding properties of three polyphenol stilbenes (desoxyrhaponticin, rhaponticin, rhapontigenin) from fenugreek. As the first step, molecular docking was performed to assess the binding potential of the fenugreek phytochemicals with IL2Rα. All three phytochemicals demonstrated interactions with active site residues. To confirm the reliability of our molecular docking results, 100 ns molecular dynamics simulations studies were undertaken. As discerned by the RMSD and RMSF analyses, IL2Rα in complex with the desoxyrhaponticin, rhaponticin, and rhapontigenin indicated stability. The RMSD analysis of the phytochemicals alone also demonstrated no significant structural changes. Based on the stable molecular interactions and comparatively slightly better MM/PBSA binding free energy, rhaponticin seems promising. Additionally, ADMET analysis performed for the stilbenes indicated that all of them obey the ADMET rules. Our computational study thus supports further in vitro IL2Rα binding studies on these stilbenes, especially rhaponticin. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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13 pages, 7453 KiB

Open AccessArticle

Targeting Cytotoxin-Associated Antigen A, a Virulent Factor of Helicobacter pylori-Associated Gastric Cancer: Structure-Based In Silico Screening of Natural Compounds

by Shan He, Abdulraheem Ali Almalki, Misbahuddin M. Rafeeq, Ziaullah M. Sain, Amany I. Alqosaibi, Mashael M. Alnamshan, Ibtesam S. Al-Dhuayan, Abdul Rahaman, Yang Zhang, Hamsa Jameel Banjer, Farah Anjum, Haitham Ali M. Alzghaibi, Ali H. Alharbi and Qazi Mohammad Sajid Jamal

Molecules 2022, 27(3), 732; https://doi.org/10.3390/molecules27030732 - 23 Jan 2022

Cited by 4 | Viewed by 3181

Abstract

Gastric cancer is the fifth most frequent cancer and the third major cause of mortality worldwide. Helicobacter pylori, a bacterial infection linked with GC, injects the cytotoxin-associated antigen A (CagA; an oncoprotein) into host cells. When the phosphorylated CagA protein enters the [...] Read more.

Gastric cancer is the fifth most frequent cancer and the third major cause of mortality worldwide. Helicobacter pylori, a bacterial infection linked with GC, injects the cytotoxin-associated antigen A (CagA; an oncoprotein) into host cells. When the phosphorylated CagA protein enters the cell, it attaches to other cellular components, interfering with normal cellular signaling pathways. CagA plays an important role in the progression of GC by interacting with phosphatidylserine of the host cell membrane. Therefore, disrupting the CagA–phosphatidylserine connection using small molecules appears to be a promising therapeutic approach. In this report, we screened the natural compounds from ZINC database against the CagA protein using the bioinformatics tools. Hits were initially chosen based on their physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics, as well as other drug-like characteristics. To locate safe and effective hits, the PAINS filter, binding affinities estimation, and interaction analysis were used. Three compounds with high binding affinity and specificity for the CagA binding pocket were discovered. The final hits, ZINC153731, ZINC69482055, and ZINC164387, were found to bind strongly with CagA protein, with binding energies of −11.53, −10.67, and −9.21 kcal/mol, respectively, which were higher than that of the control compound (−7.25 kcal/mol). Further, based on binding affinity and interaction pattern, two leads (ZINC153731, ZINC69482055) were chosen for molecular dynamics (MD) simulation analysis. MD results showed that they displayed stability in their vicinity at 100 ns. This study suggested that these compounds could be used as possible inhibitors of CagA protein in the fight against GC. However, additional benchwork tests are required to validate them as CagA protein inhibitors. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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25 pages, 6124 KiB

Open AccessArticle

Can Artemisia herba-alba Be Useful for Managing COVID-19 and Comorbidities?

by Anamul Hasan, Partha Biswas, Tohmina Afroze Bondhon, Khoshnur Jannat, Tridib K. Paul, Alok K. Paul, Rownak Jahan, Veeranoot Nissapatorn, Tooba Mahboob, Polrat Wilairatana, Md Nazmul Hasan, Maria de Lourdes Pereira, Christophe Wiart and Mohammed Rahmatullah

Molecules 2022, 27(2), 492; https://doi.org/10.3390/molecules27020492 - 13 Jan 2022

Cited by 16 | Viewed by 3976

Abstract

The focus of this roadmap is to evaluate the possible efficacy of Artemisia herba-alba Asso. (Asteraceae) for the treatment of COVID-19 and some of its symptoms and several comorbidities using a combination of in silico (molecular docking) studies, reported ethnic uses, and pharmacological [...] Read more.

The focus of this roadmap is to evaluate the possible efficacy of Artemisia herba-alba Asso. (Asteraceae) for the treatment of COVID-19 and some of its symptoms and several comorbidities using a combination of in silico (molecular docking) studies, reported ethnic uses, and pharmacological activity studies of this plant. In this exploratory study, we show that various phytochemicals from Artemisia herba-alba can be useful against COVID-19 (in silico studies) and for its associated comorbidities. COVID-19 is a new disease, so reports of any therapeutic treatments against it (traditional or conventional) are scanty. On the other hand, we demonstrate, using Artemisia herba-alba as an example, that through a proper search and identification of medicinal plant(s) and their phytochemicals identification using secondary data (published reports) on the plant’s ethnic uses, phytochemical constituents, and pharmacological activities against COVID-19 comorbidities and symptoms coupled with the use of primary data obtained from in silico (molecular docking and molecular dynamics) studies on the binding of the selected plant’s phytochemicals (such as: rutin, 4,5-di-O-caffeoylquinic acid, and schaftoside) with various vital components of SARS-CoV-2, it may be possible to rapidly identify plants that are suitable for further research regarding therapeutic use against COVID-19 and its associated symptoms and comorbidities. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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21 pages, 4159 KiB

Open AccessArticle

A Report on Multi-Target Anti-Inflammatory Properties of Phytoconstituents from Monochoria hastata (Family: Pontederiaceae)

by Md Mazedul Haq, Md Arifur Rahman Chowdhury, Hilal Tayara, Ibrahim Abdelbaky, Md Shariful Islam, Kil To Chong and Sangyun Jeong

Molecules 2021, 26(23), 7397; https://doi.org/10.3390/molecules26237397 - 06 Dec 2021

Cited by 2 | Viewed by 2259

Abstract

This study aims to investigate the potential analgesic properties of the crude extract of Monochoria hastata (MH) leaves using in vivo experiments and in silico analysis. The extract, in a dose-dependent manner, exhibited a moderate analgesic property (~54% pain inhibition in acetic acid-induced [...] Read more.

This study aims to investigate the potential analgesic properties of the crude extract of Monochoria hastata (MH) leaves using in vivo experiments and in silico analysis. The extract, in a dose-dependent manner, exhibited a moderate analgesic property (~54% pain inhibition in acetic acid-induced writhing test), which is significant (** p < 0.001) as compared to the control group. The complex inflammatory mechanism involves diverse pathways and they are inter-connected. Therefore, multiple inflammatory modulator proteins were selected as the target for in silico analysis. Computational analysis suggests that all the selected targets had different degrees of interaction with the phytochemicals from the extract. Rutin (RU), protocatechuic acid (PA), vanillic acid (VA), and ferulic acid (FA) could regulate multiple targets with a robust efficiency. None of the compounds showed selectivity to Cyclooxygenase-2 (COX-2). However, regulation of COX and lipoxygenase (LOX) cascade by PA can reduce non-steroidal analgesic drugs (NSAIDs)-related side effects, including asthma. RU showed robust regulation of cytokine-mediated pathways like RAS/MAPK and PI3K/NF-kB by inhibition of EGFR and IKBα (IKK), which may prevent multi-organ failure due to cytokine storm in several microbial infections, for example, SARS-CoV-2. Further investigation, using in vivo and in vitro experiments, can be conducted to develop multi-target anti-inflammatory drugs using the isolated compounds from the extract. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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14 pages, 7782 KiB

Open AccessArticle

Identification of Potent Natural Resource Small Molecule Inhibitor to Control Vibrio cholera by Targeting Its Outer Membrane Protein U: An In Silico Approach

by Abdul Rahaman, Abdulraheem Ali Almalki, Misbahuddin M. Rafeeq, Omar Akhtar, Farah Anjum, Mutaib M. Mashraqi, Ziaullah M. Sain, Ahmad Alzamami, Varish Ahmad, Xin-An Zeng and Qazi Mohammad Sajid Jamal

Molecules 2021, 26(21), 6517; https://doi.org/10.3390/molecules26216517 - 28 Oct 2021

Cited by 2 | Viewed by 2074

Abstract

Vibrio cholerae causes the diarrheal disease cholera which affects millions of people globally. The outer membrane protein U (OmpU) is the outer membrane protein that is most prevalent in V. cholerae and has already been recognized as a critical component of pathogenicity involved [...] Read more.

Vibrio cholerae causes the diarrheal disease cholera which affects millions of people globally. The outer membrane protein U (OmpU) is the outer membrane protein that is most prevalent in V. cholerae and has already been recognized as a critical component of pathogenicity involved in host cell contact and as being necessary for the survival of pathogenic V. cholerae in the host body. Computational approaches were used in this study to screen a total of 37,709 natural compounds from the traditional Chinese medicine (TCM) database against the active site of OmpU. Following a sequential screening of the TCM database, we report three lead compounds—ZINC06494587, ZINC85510056, and ZINC95910434—that bind strongly to OmpU, with binding affinity values of −8.92, −8.12, and −8.78 kcal/mol, which were higher than the control ligand (−7.0 kcal/mol). To optimize the interaction, several 100 ns molecular dynamics simulations were performed, and the resulting complexes were shown to be stable in their vicinity. Additionally, these compounds were predicted to have good drug-like properties based on physicochemical properties and ADMET assessments. This study suggests that further research be conducted on these compounds to determine their potential use as cholera disease treatment. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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15 pages, 88326 KiB

Open AccessArticle

In Vitro Anti-Tubulin Activity on MCF10A Cell Line and In Silico Rigid/Semiflexible-Residues Docking, of Two Lignans from Bursera Fagaroides var. Fagaroides

by Verónica Rodríguez-López, César Millán-Pacheco, Judith González-Christen, Maricruz Anaya-Ruíz and Omar Aristeo Peña-Morán

Molecules 2021, 26(20), 6155; https://doi.org/10.3390/molecules26206155 - 12 Oct 2021

Cited by 2 | Viewed by 1577

Abstract

Podophyllotoxins are natural lignans with known cytotoxic activity on several cell lines. The structural basis for their actions is mainly by the aryltetralin-lignan skeleton. Authors have proposed a cytotoxic mechanism of podophyllotoxins through the topoisomerase-II inhibition activity; however, several studies have also suggested [...] Read more.

Podophyllotoxins are natural lignans with known cytotoxic activity on several cell lines. The structural basis for their actions is mainly by the aryltetralin-lignan skeleton. Authors have proposed a cytotoxic mechanism of podophyllotoxins through the topoisomerase-II inhibition activity; however, several studies have also suggested that podophyllotoxins can inhibit the microtubules polymerization. In this work, the two possible mechanisms of action of two previously isolated compounds from the stem bark of Bursera fagaroides var. fagaroides: acetylpodophyllotoxin (1) and 5’-desmethoxydeoxypodophyllotoxin (2), was analyzed. An in vitro anti-tubulin epifluorescence on the MCF10A cell line and enzymatic topoisomerase II assays were performed. The binding affinities of compounds 1 and 2 in the colchicine binding site of tubulin by using rigid- and semiflexible-residues were calculated and compared using in silico docking methods. The two lignans were active by the in vitro anti-tubulin assay but could not inhibit TOP2 activity. In the in silico analysis, the binding modes of compounds into both rigid- and semiflexible-residues of tubulin were predicted, and only for the semiflexible docking method, a linear correlation between the dissociation constant and IC₅₀ previously reported was found. Our results suggest that a simple semiflexible-residues modification in docking methods could provide an in vitro correlation when analyzing very structurally similar compounds. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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13 pages, 3082 KiB

Open AccessArticle

Computational Screening of Natural Compounds for Identification of Potential Anti-Cancer Agents Targeting MCM7 Protein

by Mohammad Y. Alshahrani, Kholoud M. Alshahrani, Munazzah Tasleem, Arshiya Akeel, Tahani M. Almeleebia, Irfan Ahmad, Mohammed Asiri, Najla A. Alshahrani, Nadiyah M. Alabdallah and Mohd Saeed

Molecules 2021, 26(19), 5878; https://doi.org/10.3390/molecules26195878 - 28 Sep 2021

Cited by 13 | Viewed by 3128

Abstract

Minichromosome maintenance complex component 7 (MCM7) is involved in replicative licensing and the synthesis of DNA, and its overexpression is a fascinating biomarker for various cancer types. There is currently no effective agent that can prevent the development of cancer caused by the [...] Read more.

Minichromosome maintenance complex component 7 (MCM7) is involved in replicative licensing and the synthesis of DNA, and its overexpression is a fascinating biomarker for various cancer types. There is currently no effective agent that can prevent the development of cancer caused by the MCM7 protein. However, on the molecular level, inhibiting MCM7 lowers cancer-related cellular growth. With this purpose, this study screened 452 biogenic compounds extracted from the UEFS Natural Products dataset against MCM protein by using the in silico art of technique. The hit compounds UEFS99, UEFS137, and UEFS428 showed good binding with the MCM7 protein with binding energy values of −9.95, −8.92, and −8.71 kcal/mol, which was comparatively higher than that of the control compound ciprofloxacin (−6.50). The hit (UEFS99) with the minimum binding energy was picked for molecular dynamics (MD) simulation investigation, and it demonstrated stability at 30 ns. Computational prediction of physicochemical property evaluation revealed that these hits are non-toxic and have good drug-likeness features. It is suggested that hit compounds UEFS99, UEFS137, and UEFS428 pave the way for further bench work validation in novel inhibitor development against MCM7 to fight the cancers. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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19 pages, 10980 KiB

Open AccessArticle

Identification of 3-((1-(Benzyl(2-hydroxy-2-phenylethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrazine-2-carboxylic Acid as a Potential Inhibitor of Non-Nucleosidase Reverse Transcriptase Inhibitors through InSilico Ligand- and Structure-Based Approaches

by Deepti Mathpal, Tahani M. Almeleebia, Kholoud M. Alshahrani, Mohammad Y. Alshahrani, Irfan Ahmad, Mohammed Asiri, Mehnaz Kamal, Talha Jawaid, Swayam Prakash Srivastava, Mohd Saeed and Vishal M. Balaramnavar

Molecules 2021, 26(17), 5262; https://doi.org/10.3390/molecules26175262 - 30 Aug 2021

Viewed by 1777

Abstract

Non-nucleosidase reverse transcriptase inhibitors (NNRTIs) are highly promising agents for use in highly effective antiretroviral therapy. We implemented a rational approach for the identification of promising NNRTIs based on the validated ligand- and structure-based approaches. In view of our state-of-the-art techniques in drug [...] Read more.

Non-nucleosidase reverse transcriptase inhibitors (NNRTIs) are highly promising agents for use in highly effective antiretroviral therapy. We implemented a rational approach for the identification of promising NNRTIs based on the validated ligand- and structure-based approaches. In view of our state-of-the-art techniques in drug design and discovery utilizing multiple modeling approaches, we report here, for the first time, quantitative pharmacophore modeling (HypoGen), docking, and in-house database screening approaches in the identification of potential NNRTIs. The validated pharmacophore model with three hydrophobic groups, one aromatic ring group, and a hydrogen-bond acceptor explains the interactions at the active site by the inhibitors. The model was implemented in pharmacophore-based virtual screening (in-house and commercially available databases) and molecular docking for prioritizing the potential compounds as NNRTI. The identified leads are in good corroboration with binding affinities and interactions as compared to standard ligands. The model can be utilized for designing and identifying the potential leads in the area of NNRTIs. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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Review

Jump to: Research

14 pages, 1741 KiB

Open AccessReview

Potential Effects of Geraniol on Cancer and Inflammation-Related Diseases: A Review of the Recent Research Findings

by Rebai Ben Ammar

Molecules 2023, 28(9), 3669; https://doi.org/10.3390/molecules28093669 - 23 Apr 2023

Cited by 4 | Viewed by 3139

Abstract

Geraniol (GNL), a natural monoterpene, is found in many essential oils of fruits, vegetables, and herbs, including lavender, citronella, lemongrass, and other medicinal and aromatic plants. GNL is commonly used by the cosmetic and food industries and has shown a wide spectrum of [...] Read more.

Geraniol (GNL), a natural monoterpene, is found in many essential oils of fruits, vegetables, and herbs, including lavender, citronella, lemongrass, and other medicinal and aromatic plants. GNL is commonly used by the cosmetic and food industries and has shown a wide spectrum of pharmacological activities including anti-inflammatory, anticancer, antimicrobial, antioxidant, and neuroprotective activities. It represents a potential anti-inflammatory agent and a promising cancer chemopreventive agent, as it has been found to be effective against a broad range of cancers, including colon, prostate, breast, lung, skin, kidney, liver, and pancreatic cancer. Moreover, GNL scavenges free radicals and preserves the activity of antioxidant enzymes. In addition, GNL induces apoptosis and cell cycle arrest, modulates multiple molecular targets, including p53 and STAT3, activates caspases, and modulates inflammation via transcriptional regulation. In the present study, different modes of action are described for GNL’s activity against cancer and inflammatory diseases. This compound protects various antioxidant enzymes, such as catalase, glutathione-S-transferase, and glutathione peroxidase. Experiments using allergic encephalomyelitis, diabetes, asthma, and carcinogenesis models showed that GNL treatment had beneficial effects with low toxicity. GNL has been shown to be effective in animal models and tumor cell lines, but there have not been any clinical studies carried out for it. The aim of the present review is to provide updated data on the potential effects of GNL on cancer and inflammation, and to enhance our understanding of molecular targets, involved pathways, and the possible use of GNL for clinical studies and therapeutic purposes in the treatment of cancer and inflammation-related diseases. Full article

(This article belongs to the Special Issue Bioactivities and In Silico Study of Phytochemicals)

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