Analysis Of Anticancer Activity And Its Molecular Interaction Mechanism Of Withanone, An Active Ingredient Of Withania Somnifera Using Molecular Docking

Withania somnifera is an annual evergreen shrub from the Solanaceae family, commonly known as Indian ginseng or Ashwagandha. The plant is mainly found in Asia and Africa regions. In the traditional Indian medicinal system ayurveda, Withania somnifera is used as a rejuvenator and sold in many countries as a dietary supplement. Withanolides are the major phytochemical constituent group found in the Withania somnifera, among which withaferin A and withanone, are considered to be major withanolides, which believed to be involved in majority of biological activity of Withania somnifera. Various studies including both in vitro and in vivo have reported regarding the anticancer potential of Withania somnifera. Along with the anticancer activity of W.somnifera, the anticancer efficacy of one of its major ingredients Withaferin A is also studied previously. This study aimed to analyse the anticancer potential of another major Withanolide present in W. Somnifera, Withanone. The study used Molecular Docking method to find the molecular binding affinity of Withanone towards various cancer proteins. The four major cancer proteins were B-cell lymphoma- extra large (Bcl-xL), Cellular FLICE (c-FLIP), Glutathione Reductase (GR) and Glutathione S- Transferases (GST). The protein structure obtained from the protein data bank and the structure of the molecule obtained from pubchem were modified and prepared for Docking studies with the help of MGL Tools. The protein ligand interaction study was conducted using the software, Autodock vina. The already known anticancer standard, 5-FluoroUracil is used as standard for comparison. Output obtained from the study is visualised using molecular visualiser tool, Pymol. Like the Withaferin A, Withanone also exhibited promising anticancer activity while studied using molecular docking methods.

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Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies

Molecules ◽

10.3390/molecules26226990 ◽

2021 ◽

Vol 26 (22) ◽

pp. 6990

Author(s):

Hamid Saeed Shah ◽

Usman Nasrullah ◽

Sumera Zaib ◽

Faisal Usman ◽

Ajmal Khan ◽

...

Keyword(s):

Anticancer Activity ◽

Tumour Volume ◽

Docking Studies ◽

Withaferin A ◽

Target Cells ◽

Scanning Calorimetry ◽

Dapi Staining ◽

Anticancer Efficacy

The rapidly growing global burden of cancer poses a major challenge to public health and demands a robust approach to access promising anticancer therapeutics. In parallel, nanotechnology approaches with various pharmacological properties offer efficacious clinical outcomes. The use of new artificial variants of nanosponges (NS) as a transporter of chemotherapeutic drugs to target cells has emerged as a very promising tool. Therefore, in this research, ethylcellulose (EC) NS were prepared using the ultrasonication assisted-emulsion solvent evaporation technique. Withaferin-A (WFA), an active ingredient in Withania somnifera, has been implanted into the nanospongic framework with enhanced anticancer properties. Inside the polymeric structure, WFA was efficiently entrapped (85 ± 11%). The drug (WFA) was found to be stable within polymeric nanosponges, as demonstrated by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies. The WFA-NS had a diameter of 117 ± 4 nm and zeta potential of −39.02 ± 5.71 mV with a polydispersity index (PDI) of 0.419 ± 0.073. In addition, scanning electron microscopy (SEM) revealed the porous surface texture of WFA-NS. In vitro anticancer activity (SRB assay) results showed that WFA–NS exhibited almost twice the anticancer efficacy against MCF-7 cells (IC50 = 1.57 ± 0.091 µM), as quantified by flow cytometry and comet tests. Moreover, fluorescence microscopy with DAPI staining and analysis of DNA fragmentation revealed apoptosis as a mechanism of cancer cell death. The anticancer activity of WFA-NS was further determined in vivo and results were compared to cisplatin. The anticancer activity of WFA-NS was further investigated in vivo, and the data were consistent to those obtained with cisplatin. At Day 10, WFA-NS (10 mg/kg) significantly reduced tumour volume to 72 ± 6%, which was comparable to cisplatin (10 mg/kg), which reduced tumour volume to 78 ± 8%. Finally, the outcomes of molecular modeling (in silico) also suggested that WFA established a stable connection with nanosponges, generating persistent hydrophobic contacts (polar and nonpolar) and helping with the attractive delayed-release features of the formulation. Collectively, all the findings support the use of WFA in nanosponges as a prototype for cancer treatment, and opened up new avenues for increasing the efficacy of natural product-derived medications.

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Anticancer Activity Of Plant Genus Clerodendrum (Lamiaceae): A Review

Majalah Obat Tradisional ◽

10.22146/mot.31554 ◽

2017 ◽

Vol 22 (3) ◽

pp. 182

Author(s):

Donald Emilio Kalonio ◽

Rini Hendriani ◽

Elisabeth N. Barung

Keyword(s):

Molecular Docking ◽

Anticancer Activity ◽

Docking Simulation ◽

Scientific Data ◽

Anticancer Effect ◽

Literature Study ◽

Molecular Docking Simulation ◽

Chemical Content

Plants of the genus Clerodendrum (Lamiaceae) is widespread in tropical and subtropical regions. Plants of this genus are used both empirically and scientifically as anti-inflammatory, antidiabetic, antimalarial, antiviral, antihypertensive, hypolipidemic, antioxidant, and antitumor. Results of the molecular docking simulation of chemical content of these plants could potentially provide an anticancer effect. This paper aims to review the anticancer activity of plant genus Clerodendrum based on scientific data. The method used in this study is the literature study. Searches were conducted online (in the database PubMed, Science Direct and Google Scholar) and on various books (Farmakope Herbal Indonesia and PROSEA). A total 12 plants of the genus Clerodendrum have anticancer activity in vitro and in vivo, thus potentially to be developed as a source of new active compounds with anticancer activity.

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CISSAMPELOS PAREIRA: PROTEIN-LIGAND DOCKING TO IDENTIFY SUITABLE TARGETS FOR HEPATOCELLULAR CARCINOMA (HCC) BY IN-SILICO TECHNIQUES AND TOOLS

Jurnal Teknologi ◽

10.11113/jt.v77.5982 ◽

2015 ◽

Vol 77 (2) ◽

Author(s):

B. Samuel Thavamani ◽

Molly Mathew ◽

Dhanabal S. Palaniswamy

Keyword(s):

Hepatocellular Carcinoma ◽

Growth Factor ◽

In Silico ◽

B Cell Lymphoma ◽

Aurora Kinase ◽

Pharmacological Action ◽

Ligand Docking ◽

Ligand Interaction

Protein-ligand interaction plays a major role in identification of the possible mechanism by which a ligand can bind with the target and exerts the pharmacological action. The present study aims to identify new possible candidates for treating Hepatocellular Carcinoma (HCC) by docking the reported phytochemicals present in Cissampelos pareira with the well known HCC targets using in-silico techniques. Although C. pareira demonstrated in vitro and in vivo anti-heptatocellular carcinoma activities, the mechanism remains uncertain. Selected compounds from C. pareira were docked using GLIDE software with known targets of hepatocellular carcinoma viz. Aurora Kinase, c-Kit, Fibroblast Growth Factor (FGF), Nuclear Factor kappa B (NF-kB), B-cell lymphoma-extra large (Bcl-xL) and Vascular Endothelial Growth Factor (VEGF). Among the compounds docked, pareitropone and pareirubrine B exhibited good hydrogen bonding interactions and binding energy with the targets of HCC taken in the study. Hence these compounds deserve consideration for further studies towards HCC.

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Withaferin A—A Promising Phytochemical Compound with Multiple Results in Dermatological Diseases

Molecules ◽

10.3390/molecules26092407 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2407

Author(s):

Simona Bungau ◽

Cosmin Mihai Vesa ◽

Areha Abid ◽

Tapan Behl ◽

Delia Mirela Tit ◽

...

Keyword(s):

Mechanism Of Action ◽

In Silico ◽

Withania Somnifera ◽

In Vivo Studies ◽

Withaferin A ◽

Biological Targets ◽

Dermatological Diseases ◽

Anticancer Effects

Withaferin A (WFA) was identified as the most active phytocompound of the plant Withania somnifera (WS) and as having multiple therapeutic/ameliorating properties (anticancer, antiangiogenic, anti-invasive, anti-inflammatory, proapoptotic, etc.) in case of various diseases. In drug chemistry, WFA in silico approaches have identified favorite biological targets, stimulating and accelerating research to evaluate its pharmacological activity—numerous anticancer effects manifested in various organs (breast, pancreas, skin, colon, etc.), antivirals, anti-infective, etc., which are not yet sufficiently explored. This paper is a synthesis of the most relevant specialized papers in the field that are focused on the use of WFA in dermatological diseases, describing its mechanism of action while providing, at the same time, details about the results of its testing in in vitro/in vivo studies.

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Anticancer Mechanism of Withania Somnifera and Its Bioactive Compounds : A Short Review Along with Computational Molecular Docking Study

10.26434/chemrxiv.13038236.v1 ◽

2020 ◽

Author(s):

Mita Shikder ◽

Tasnin Al Hasib ◽

Md. Lutful Kabir

Keyword(s):

Molecular Docking ◽

Anticancer Activity ◽

Bioactive Compounds ◽

Withania Somnifera ◽

Short Review ◽

Docking Study ◽

Withaferin A ◽

Molecular Docking Study ◽

Anticancer Mechanism ◽

Protein Kinase C Iota

<p>Withania somnifera, known as Aswogondha in Bangladesh and some part of India, is a shrub of Solanceae family. Parts of this plant is used as alternative medicine in this region to cure diseases from bronchitis to insomnia. Although such use of the plant is not supported by clinical research, recent studies have found anticancer activity of some proteins derived from w. somnifera. The purpose of this study is to summarize the anticancer activity of medicinal plant Withania somnifera and its bioactive compounds as well as to predict the interaction between phytochemicals (Withanolide, Withaferin-A) and macromolecules that are responsible for cancer cell proliferation. Studies suggested that Withanolide and Withaferin-A from W. somnifera can be used as a cancer chemotherapeutic agent for cancerous cell lines in mice models through modulating various signaling pathway including inhibition, autophagy, apoptosis, radiopreventive pathway and reactive oxygen species pathway. Molecular docking of Withanolide and Withaferin-A against 9 types of vital protein mediators concluded that 3A8X (Protein kinase C iota type) and 1A9U (MAP KINASE P38) are the most active receptor for binding and interacting with Withanolide and Withaferin-A for the prevention and treatment of cancer. On the basis of this review and docking study, it can be concluded that Withania somnifera as well as its derivatives Withanolide and Withaferin-A may be considered as a promising anticancer agent. </p>

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Anticancer Mechanism of Withania Somnifera and Its Bioactive Compounds : A Short Review Along with Computational Molecular Docking Study

10.26434/chemrxiv.13038236 ◽

2020 ◽

Author(s):

Mita Shikder ◽

Tasnin Al Hasib ◽

Md. Lutful Kabir

Keyword(s):

Molecular Docking ◽

Anticancer Activity ◽

Bioactive Compounds ◽

Withania Somnifera ◽

Short Review ◽

Docking Study ◽

Withaferin A ◽

Molecular Docking Study ◽

Anticancer Mechanism ◽

Protein Kinase C Iota

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Vitamin D as potential therapeutic anticancer agent

Journal of Cancer Science and Therapeutics ◽

10.36879/jcst.19.000106 ◽

2018 ◽

pp. 1-3

Keyword(s):

Vitamin D ◽

Anticancer Activity ◽

Anticancer Agent ◽

Antitumor Agents ◽

Metastatic Potential ◽

Anticancer Properties ◽

Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

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Action of Thioglycosides of 1,2,4-Triazoles and Imidazoles on the Oxidative Stress and Glycosidases in Mice with Molecular Docking

Letters in Drug Design & Discovery ◽

10.2174/1573413715666181212150955 ◽

2019 ◽

Vol 16 (6) ◽

pp. 696-710

Author(s):

Mahmoud Balbaa ◽

Doaa Awad ◽

Ahmad Abd Elaal ◽

Shimaa Mahsoub ◽

Mayssaa Moharram ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Docking ◽

Active Sites ◽

Biological Activities ◽

Imidazole Ring ◽

Quantitative Structure Activity Relationship ◽

Binding Interaction ◽

Qsar Study

Background: ,2,3-Triazoles and imidazoles are important five-membered heterocyclic scaffolds due to their extensive biological activities. These products have been an area of growing interest to many researchers around the world because of their enormous pharmaceutical scope. Methods: The in vivo and in vitro enzyme inhibition of some thioglycosides encompassing 1,2,4- triazole N1, N2, and N3 and/or imidazole moieties N4, N5, and N6. The effect on the antioxidant enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) was investigated as well as their effect on α-glucosidase and β-glucuronidase. Molecular docking studies were carried out to investigate the mode of the binding interaction of the compounds with α- glucosidase and β -glucuronidase. In addition, quantitative structure-activity relationship (QSAR) investigation was applied to find out the correlation between toxicity and physicochemical properties. Results: The decrease of the antioxidant status was revealed by the in vivo effect of the tested compounds. Furthermore, the in vivo and in vitro inhibitory effects of the tested compounds were clearly pronounced on α-glucosidase, but not β-glucuronidase. The IC50 and Ki values revealed that the thioglycoside - based 1,2,4-triazole N3 possesses a high inhibitory action. In addition, the in vitro studies demonstrated that the whole tested 1,2,4-triazole are potent inhibitors with a Ki magnitude of 10-6 and exhibited a competitive type inhibition. On the other hand, the thioglycosides - based imidazole ring showed an antioxidant activity and exerted a slight in vivo stimulation of α-glucosidase and β- glucuronidase. Molecular docking proved that the compounds exhibited binding affinity with the active sites of α -glucosidase and β-glucuronidase (docking score ranged from -2.320 to -4.370 kcal/mol). Furthermore, QSAR study revealed that the HBD and RB were found to have an overall significant correlation with the toxicity. Conclusion: These data suggest that the inhibition of α-glucosidase is accompanied by an oxidative stress action.

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Alkaloids as Anticancer Agents: A Review of Chinese Patents in Recent 5 Years

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892815666200131120618 ◽

2020 ◽

Vol 15 (1) ◽

pp. 2-13 ◽

Cited By ~ 3

Author(s):

Hongyu Tao ◽

Ling Zuo ◽

Huanli Xu ◽

Cong Li ◽

Gan Qiao ◽

...

Keyword(s):

Anticancer Activity ◽

Anticancer Agents ◽

Kinase Inhibitors ◽

Protein Kinase Inhibitors ◽

Cdk Inhibitors ◽

Comprehensive Overview ◽

P53 Expression ◽

Study Results

Background: In recent years, many novel alkaloids with anticancer activity have been found in China, and some of them are promising for developing as anticancer agents. Objective: This review aims to provide a comprehensive overview of the information about alkaloid anticancer agents disclosed in Chinese patents, and discusses their potential to be developed as anticancer drugs used clinically. Methods: Anticancer alkaloids disclosed in Chinese patents in recent 5 years were presented according to their mode of actions. Their study results published on PubMed, and SciDirect databases were presented. Results: More than one hundred anticancer alkaloids were disclosed in Chinese patents and their mode of action referred to arresting cell cycle, inhibiting protein kinases, affecting DNA synthesis and p53 expression, etc. Conclusion: Many newly found alkaloids displayed potent anticancer activity both in vitro and in vivo, and some of the anticancer alkaloids acted as protein kinase inhibitors or CDK inhibitors possess the potential for developing as novel anticancer agents.

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Anticancer Activity of Triazolo-Thiadiazole Derivatives and Inhibition of AKT1 and AKT2 Activation

Pharmaceutics ◽

10.3390/pharmaceutics13040493 ◽

2021 ◽

Vol 13 (4) ◽

pp. 493

Author(s):

Dimitrios T. Trafalis ◽

Sofia Sagredou ◽

Panayiotis Dalezis ◽

Maria Voura ◽

Stella Fountoulaki ◽

...

Keyword(s):

Anticancer Activity ◽

Human Colon ◽

Tumor Xenograft ◽

Atp Binding Site ◽

Anticancer Properties ◽

Extensive Range ◽

Dependent Inhibition ◽

Ht 29

The fusion of 1,2,4-triazole and 1,3,4-thiadiazole rings results in a class of heterocycles compounds with an extensive range of pharmacological properties. A series of 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles was synthesized and tested for its enzyme inhibition potential and anticancer activity. The results show that 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles display potent anticancer properties in vitro against a panel of cancer cells and in vivo efficacy in HT-29 human colon tumor xenograft in CB17 severe combined immunodeficient (SCID) mice. Preliminary mechanistic studies revealed that KA25 and KA39 exhibit time- and concentration-dependent inhibition of Akt Ser-473 phosphorylation. Molecular modeling experiments indicated that 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles bind well to the ATP binding site in Akt1 and Akt2. The low acute toxicity combined with in vitro and in vivo anticancer activity render triazolo[3,4-b]thiadiazoles KA25, KA26, and KA39 promising cancer therapeutic agents.

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