scholarly journals VIRTUAL SCREENING AND IDENTIFICATION OF PLAUSIBLE NOVEL THERAPEUTIC EGFR INHIBITORS AGAINST BREAST CANCER

2021 ◽  
Vol 9 (4) ◽  
pp. 481-491
Author(s):  
Megana KSNM ◽  
◽  
Suneetha Y ◽  
Keyword(s):  
Breast Cancer ◽  
Virtual Screening ◽  
Anticancer Agents ◽  
Docking Studies ◽  
The Novel ◽  
Drug Candidates ◽  
Promising Target ◽  
Toxic Drug ◽  
Screening And Identification ◽  
Novel Drug

Present days increasing concern about the identification of potential non-toxic drug candidates against several cancers is very important. The current study was carried out to discover the novel phytochemicals as effective anticancer agents against the selected protein (i.e., EGFR), which is a promising target for moderating triple-negative breast cancer (TNBC). Various studies showed that the natural constituents have a strong anti-tumor capacity and inhibiting tumor growth. Here structure-based virtual screening and molecular docking studies have been recognized as rational tactics for the recognition of novel drug candidates against the binding domain of EGFR (PDB code: 3GKW & 5FEE). Furthermore, the drug-likeness, adverse effects, and toxicogenomics effects were assessed with the help of various computational tools. Virtual screening was reported that 4 drug candidates i.e., CID: 65064; CID: 5280443; CID: 440735, and CID: 5280343 showed reliable consequences with fewer side effects and more efficient for the selected proteins. The overall effects indicated that renowned hits could be developed as reference skeletons for novel inhibitors envisaging EGFR to ameliorate TNBC.

scholarly journals Homology Modeling and Virtual Screening Studies of Antigen MLAA-42 Protein: Identification of Novel Drug Candidates against Leukemia—An In Silico Approach

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Ihsan A. Shehadi ◽  
Huda R. M. Rashdan ◽  
Aboubakr H. Abdelmonsef
Keyword(s):  
Virtual Screening ◽  
Homology Modeling ◽  
Protein Identification ◽  
Binding Affinities ◽  
Monocytic Leukemia ◽  
Drug Candidates ◽  
Promising Target ◽  
Leukemia Treatment ◽  
Potent Drug ◽  
Novel Drug

Monocytic leukemia-associated antigen-42 (MLAA-42) is associated with excessive cell division and progression of leukemia. Thus, human MLAA-42 is considered as a promising target for designing of new lead molecules for leukemia treatment. Herein, the 3D model of the target was generated by homology modeling technique. The model was then evaluated using various cheminformatics servers. Moreover, the virtual screening studies were performed to explore the possible binding patterns of ligand molecules to MLAA’s active site pocket. Thirteen ligand molecules from the ChemBank™ database were identified as they showed good binding affinities, scaffold diversity, and preferential ADME properties which may act as potent drug candidates against leukemia. The study provides the way to identify novel therapeutics with optimal efficacy, targeting MLAA-42.

Pharmacophore Based 3D-QSAR, Virtual Screening and Docking Studies on Novel Series of HDAC Inhibitors with Thiophen Linker as Anticancer Agents

2016 ◽  
Vol 19 (9) ◽  
pp. 735-751 ◽  
Author(s):  
Preeti Patel ◽  
Avineesh Singh ◽  
Vijay Patel ◽  
Deepak Jain ◽  
Ravichandran Veerasamy ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Anticancer Agents ◽  
Hdac Inhibitors ◽  
3D Qsar ◽  
Docking Studies

scholarly journals Full-length and C-terminal neurogranin in Alzheimer’s disease cerebrospinal fluid analyzed by novel ultrasensitive immunoassays

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Annika Öhrfelt ◽  
Julien Dumurgier ◽  
Henrik Zetterberg ◽  
Agathe Vrillon ◽  
Nicholas J. Ashton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Molecule ◽  
Full Length ◽  
The Novel ◽  
Drug Candidates ◽  
Postsynaptic Protein ◽  
Coefficients Of Variation ◽  
Assay Precision ◽  
Novel Drug

Abstract Background Neurogranin (Ng) is a neuron-specific and postsynaptic protein that is abundantly expressed in the brain, particularly in the dendritic spine of the hippocampus and cerebral cortex. The enzymatic cleavage of Ng produces fragments that are released into cerebrospinal (CSF), which have been shown to be elevated in Alzheimer’s disease (AD) patients and predict cognitive decline. Thus, quantification of distinctive cleavage products of Ng could elucidate different features of the disease. Methods In this study, we developed novel ultrasensitive single molecule array (Simoa) assays for measurement of full-length neurogranin (FL-Ng) and C-terminal neurogranin (CT-Ng) fragments in CSF. The Ng Simoa assays were evaluated in CSF samples from AD patients (N = 23), mild cognitive impairment due to AD (MCI-AD) (N = 18), and from neurological controls (N = 26). Results The intra-assay repeatability and inter-assay precision of the novel methods had coefficients of variation below 7% and 14%, respectively. CSF FL-Ng and CSF CT-Ng median concentrations were increased in AD patients (6.02 ng/L, P < 0.00001 and 452 ng/L, P = 0.00001, respectively) and in patients with MCI-AD (5.69 ng/L, P < 0.00001 and 566 ng/L, P < 0.00001) compared to neurological controls (0.644 ng/L and 145 ng/L). The median CSF ratio of CT-Ng/FL-Ng were decreased in AD patients (ratio = 101, P = 0.008) and in patients with MCI-AD (ratio = 115, P = 0.016) compared to neurological controls (ratio = 180). CSF of FL-Ng, CT-Ng, and ratio of CT-Ng/FL-Ng could each significantly differentiate AD patients from controls (FL-Ng, AUC = 0.907; CT-Ng, AUC = 0.913; CT-Ng/FL-Ng, AUC = 0.775) and patients with MCI-AD from controls (FL-Ng, AUC = 0.937; CT-Ng, AUC = 0.963; CT-Ng/FL-Ng, AUC = 0.785). Conclusions Assessments of the FL-Ng and CT-Ng levels in CSF with the novel sensitive immunoassays provide a high separation of AD from controls, even in early phase of the disease. The novel Ng assays are robust and highly sensitive and may be valuable tools to study synaptic alteration in AD, as well as to monitor the effect on synaptic integrity of novel drug candidates in clinical trials.

scholarly journals Identification of Potent VHZ Phosphatase Inhibitors with Structure-Based Virtual Screening

2012 ◽  
Vol 18 (2) ◽  
pp. 226-231 ◽  
Author(s):  
Hwangseo Park ◽  
So Ya Park ◽  
Jung Jin Oh ◽  
Seong Eon Ryu
Keyword(s):  
Virtual Screening ◽  
Active Site ◽  
Structural Features ◽  
Drug Candidate ◽  
The Novel ◽  
Anticancer Activities ◽  
Phosphatase Inhibitors ◽  
Structure Activity ◽  
Promising Target ◽  
Further Development

VH1-like phosphatase Z (VHZ) has proved to be a promising target for the development of therapeutics for the treatment of human cancers. Here, we report the first example for a successful application of structure-based virtual screening to identify the novel small-molecule inhibitors of VHZ. These inhibitors revealed high potencies with the associated IC50 values ranging from 3 to 20 µM and were also screened for having desirable physicochemical properties as a drug candidate. Therefore, they deserve consideration for further development by structure-activity relationship studies to optimize inhibitory and anticancer activities. Structural features relevant to the stabilization of the newly identified inhibitors in the active site of VHZ are discussed in detail.

Long-Lasting Control of Triple-Negative Metastatic Breast Cancer with the Novel Drug Combination Ixabepilone and Capecitabine – Case Report

Onkologie ◽  
2010 ◽  
Vol 33 (1-2) ◽  
pp. 53-56 ◽  
Author(s):  
Eduard Vrdoljak ◽  
Branka Petri&cacute; Mi&scaron;e ◽  
Blanka Luki&cacute; ◽  
Zvonimir Curi&cacute; ◽  
Lidija Bo&scaron;kovi&cacute; ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Case Report ◽  
Drug Combination ◽  
Triple Negative ◽  
Metastatic Breast ◽  
The Novel ◽  
Novel Drug

Anticancer Activity-Structure Relationship of Quinolinone-Based Compounds: An Overview

2021 ◽  
Vol 21 ◽  
Author(s):  
Hüseyin K. Beker ◽  
Işıl Yıldırım
Keyword(s):  
Functional Groups ◽  
Anticancer Agents ◽  
Drug Candidates ◽  
Activity Structure ◽  
Gene And Protein Expression ◽  
Structure Relationship ◽  
New Vision ◽  
Relationship Of ◽  
Novel Drug ◽  
Electron Donating Groups

Background: Heterocyclic compounds play an important role in the pharmaceutical and biological processes. Among all heterocycles, quinolinone/quinoline has one of the most unique structures in the discovery of these compounds. These derivatives have been prepared by various on the structures, positions, and they have attracted a great deal of attention in the field of medicinal chemistry. The great interest to medicinal chemists is the basic scaffold of the fused quinolines derivative. The large road maps of gene and protein expression produced by these methods often can be used to classify cancers or predict responses to certain types of treatments targeting regulated at both the level of transcription and translation and at the level of enzyme activity. These specific regulations may open the door for the discovery of novel drug candidates including an anti-cancer target. Objective: This review will attempt to provide a comprehensive description of different quinolinone derivatives especially by concentrating on compounds containing benzimidazole ring. Quinolones moieties are experimentally proven anticancer pharmacophores. We think these pharmacophore and additional substitutions on these scaffolds would further enhance their activity as anticancer agents. This activity associate with the positioning of these different functional groups, such as fluoro, methoxy, methyl, amino, hydroxy, nitro, bromo, chloro, methylamino, ethoxy, carbonyl, iodo, and trifluoromethyl groups. Among the functional groups, most of the electronwithdrawing groups such as fluoro, chloro, nitro, amino, and carbonyl groups showed stronger activity than those with electron-donating groups such as methyl and methoxy groups. Presence of electron-withdrawing or electron-donating group by varying the quinolinone redox properties affect its capacity of DNA synthesis. Conclusion: The structural motifs attributed to noteworthy inhibitory results have been identified and highlighted in order to encourage further research and develop more efficient. This work to aim to present knowledge and it hoped that this review can be help researchers to explore an interesting quinoline class, and researchers will be able to develop a new vision in the search for rational designs of more powerful, active and less toxic quinoline-based anticancer drugs.

scholarly journals Design, Synthesis and Apoptosis Inducing Activity of Non-steroidal Flavone- methanesulfonate Derivatives on MCF-7 cell line as Potential Sulfatase Inhibitor

2021 ◽  
Author(s):  
Mahdiyeh HS Javadi ◽  
Aida Iraji ◽  
maliheh safavi ◽  
Hamed Montazeri ◽  
Parastoo Tarighi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Anticancer Agents ◽  
Hydrophobic Interactions ◽  
Cancer Cell Line ◽  
Annexin V ◽  
Docking Studies ◽  
Hydrogen Bond Interaction ◽  
Cytotoxic Compound ◽  
Mcf 7

Abstract In recent years, focusing on new potent anticancer agents with selective activity is one of the greatest challenges in cancer therapy. Breast cancer is the most common cancer and the main cause of cancer deaths in women. The sulfatase enzyme plays an important role in converting the sulfated steroids into non-sulfate steroid hormones, which increases the growth and development of many hormone-dependent cancers, such as breast cancer. In this regard, structure-based optimization was conducted to design novel flavone-sulfonates pharmacophore as a new steroid sulfatase inhibitor. In the present work, the conventional methods for the synthesis of 4-oxo-2-phenyl-4H-chromen-7-yl methanesulfonate derivatives were reported. Their cytotoxicity was evaluated with MTT assay against a breast cancer cell line (MCF-7). The apoptosis inducing activity of the most cytotoxic compound 3c with an IC50 value of 0.615 µM was evaluated in comparison to docetaxel in the presence of estradiol which is a crucial growth factor to survive the cancerous cells. The results of double staining Annexin V-FITC/PI analysis suggested that the cytotoxic activity of this compound 3c in MCF-7 cells occurs via apoptosis. Molecular docking studies were conducted to clarify the inhibition mode of the most promising compound (3c) over the sulfatase (1P49) binding site. The analysis revealed the role of hydrogen bond interaction with Gly181 and hydrophobic interactions through the 1P49 active site in the ligand-receptor complex as significant descriptors to rationalize the potential inhibition activity.

scholarly journals In-silico protein-ligand docking studies against the estrogen protein of breast cancer using pharmacophore based virtual screening approaches

2021 ◽  
Vol 28 (1) ◽  
pp. 400-407
Author(s):  
Jesudass Joseph Sahayarayan ◽  
Kulanthaivel Soundar Rajan ◽  
Ramasamy Vidhyavathi ◽  
Mutharasappan Nachiappan ◽  
Dhamodharan Prabhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Virtual Screening ◽  
In Silico ◽  
Docking Studies ◽  
Ligand Docking ◽  
Screening Approaches

Utilization of Flavonoid Compounds as HER2 Tyrosine Kinase Inhibitor in Breast Cancer Using Fragment-Based Drug Design

2020 ◽  
Vol 840 ◽  
pp. 230-236
Author(s):  
Vincent Jonathan Fleming ◽  
Mutiara Saragih ◽  
Usman Sumo Friend Tambunan
Keyword(s):  
Breast Cancer ◽  
Drug Design ◽  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Protein Activity ◽  
Drug Candidates ◽  
Potential Alternative ◽  
Dimerization Reaction ◽  
Novel Drug

Breast cancer has become one of the leading cause of women’s death around the world. Breast cancer can be caused by genetic or environmental factors. Human epidermal growth factor receptor 2 (HER2) is one of the main causes of breast cancer. The HER2 tyrosine kinase plays a significant role in the dimerization reaction which causes auto-phosphorylation of tyrosine residues in the cytoplasmic domain that triggers growth of the cancer cells. Inhibition of HER2 protein activity can be a potential alternative for breast cancer treatment. Flavonoids have become an important scaffold in medicinal chemistry due to its bioactivity and availability. Therefore, flavonoids were used as the database on this in silico research. Fragment-based drug design was applied to determine novel drug candidates. Three potential candidates were obtained in this research. VC-962 was selected as the best inhibitor candidates for HER2 tyrosine kinase.

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