Determination of structural requirements of Mer kinase inhibitors and binding interaction analysis using in silico approaches

2016 ◽  
Vol 25 (12) ◽  
pp. 3021-3029 ◽  
Author(s):  
Anand Balupuri ◽  
Pavithra K. Balasubramanian ◽  
Seung Joo Cho
Keyword(s):  
In Silico ◽  
Kinase Inhibitors ◽  
Interaction Analysis ◽  
Binding Interaction ◽  
Structural Requirements ◽  
Mer Kinase Inhibitors

In-silico screening of 2,3-diphenylquinozaline derivatives as C-met kinase inhibitors

2017 ◽  
Vol 4 (3) ◽  
pp. 41-45
Author(s):  
Nehla Yahcoob ◽  
Baskar Lakshmanan ◽  
Jyothi Achuthanandhan ◽  
Vijayakumar Balakrishnan
Keyword(s):  
Binding Energy ◽  
Tyrosine Kinase ◽  
In Silico ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Binding Interaction ◽  
In Silico Screening ◽  
Sar Study

Quinoxaline, an important class of heterocylic compounds drawn greater attention due to their wide spectrum of biological activities. They are considered as an important chemical scaffold for anticancer drug design  due to their potential inhibitory activity against  C-met tyrosine kinase. C-met kinase inhibitors  are a class of small molecules that having therapeutic potential in  the treatment of various types of cancers. The present study aims to focus on the chemistry of quinoxaline derivatives, their potential activities against C-met tyrosine kinase, and in-silico screening of designed compounds. A series of twelve compounds were designed and docked against C-met tyrosine kinase for their binding energy. All compounds were found to be interacting  well with the protein. Compound NQ1 was found to have good binding energy showing an estimated Ki value of  1.1μm.  SAR  study indicated the presence of an electron withdrawing substitution on  benzilidine  phenyl ring of quinoxaline greatly improves its binding interaction with the protein.

scholarly journals Determination of Structural Requirements of N-Substituted Tetrahydro-β-Carboline Imidazolium Salt Derivatives Using in Silico Approaches for Designing MEK-1 Inhibitors

Molecules ◽  
2017 ◽  
Vol 22 (6) ◽  
pp. 1020 ◽  
Author(s):  
Jingwei Liang ◽  
Mingyang Wang ◽  
Xinyang Li ◽  
Xin He ◽  
Chong Cao ◽  
...  
Keyword(s):  
In Silico ◽  
Imidazolium Salt ◽  
Structural Requirements

In silico approach for designing a novel recombinant fusion protein as a Candidate Vaccine against HPV

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohsen Sisakht ◽  
Amir Mahmoodzadeh ◽  
Mohammadsaeid Zahedi ◽  
Davood Rostamzadeh ◽  
Amin Moradi Hasan-Abad ◽  
...  
Keyword(s):  
Immune Responses ◽  
Fusion Protein ◽  
In Silico ◽  
Precancerous Lesions ◽  
Candidate Vaccine ◽  
T Cell Epitopes ◽  
Binding Interaction ◽  
Hpv16 E6 ◽  
E7 Proteins

Background: Human papillomavirus (HPV) is the main biological agent causing sexually transmitted diseases (STDs), including precancerous lesions and several types of prevalent cancers. To date, numerous types of vaccines are designed to prevent high-risk HPV. However, their prophylactic effect is not the same and does not clear previous infections. Therefore, there is an urgent need for developing therapeutic vaccines that trigger cell-mediated immune responses for the treatment of HPV. The HPV16 E6 and E7 proteins are ideal targets for vaccine therapy against HPV. Fusion protein vaccines, which include both immunogenic interest protein and an adjuvant for augmenting the immunogenicity effects, are theoretically capable of guarantee the power of the immune system against HPV. Method: A vaccine construct, including HPV16 E6/E7 proteins along with a heat shock protein GP96 (E6/E7-NTGP96 construct), was designed using in silico methods. By the aid of the SWISS-MODEL server, the optimal 3D model of the designed vaccine was selected, followed by physicochemical and molecular parameters were performed using bioinformatics tools. Docking studies were done to evaluate the binding interaction of the vaccine. Allergenicity, immunogenicity, B, and T cell epitopes of the designed construct were predicted. Results: Immunological and structural computational results illustrated that our designed construct is potentially proper for stimulation of cellular and humoral immune responses against HPV. Conclusion: Computational studies showed that the E6/E7-NTGP96 construct is a promising candidate vaccine that needs further in vitro and in vivo evaluations.

A New Series of Antileukemic Agents: Design, Synthesis, In Vitro and In Silico Evaluation of Thiazole-Based ABL1 Kinase Inhibitors

2020 ◽  
Vol 20 ◽  
Author(s):  
Ebru Zeytün ◽  
Mehlika D. Altıntop ◽  
Belgin Sever ◽  
Ahmet Özdemir ◽  
Doha E. Ellakwa ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Line ◽  
Antiproliferative Activity ◽  
In Silico ◽  
K562 Cell ◽  
Kinase Inhibitors ◽  
K562 Cell Line ◽  
Cytotoxic Effects ◽  
Atp Binding Site

Background: After the milestone approval of imatinib, more than 25 antitumor agents targeting kinases have been approved, and several promising candidates are in various stages of clinical evaluation. Objectives : Due to the importance of thiazole scaffold in targeted anticancer drug discovery, the goal of this work is the design of new thiazolyl hydrazones as potent ABL1 kinase inhibitors for the management of chronic myeloid leukemia (CML). Methods: New thiazolyl hydrazones (2a-p) were synthesized and investigated for their cytotoxic effects on K562 CML cell line. Compounds 2h, 2j and 2l showed potent anticancer activity against K562 cell line. The cytotoxic effects of these compounds on other leukemia (HL-60, MT-2 and Jurkat) and HeLa human cervical carcinoma cell lines were also investigated. Furthermore, their cytotoxic effects on mitogen-activated peripheral blood mononuclear cells (MA-PBMCs) were evaluated to determine their selectivity. Due to its selective and potent anticancer activity, compound 2j was benchmarked for its apoptosis-inducing potential on K562 cell line and inhibitory effects on eight different tyrosine kinases (TKs) including ABL1 kinase. In order to investigate the binding mode of compound 2j into the ATP binding site of ABL1 kinase (PDB: 1IEP), molecular docking study was conducted using MOE 2018.01 program. The QikProp module of Schrödinger’s Molecular modelling package was used to predict the pharmacokinetic properties of compounds 2a-p. Results: 4-(4-(Methylsulfonyl)phenyl)-2-[2-((1,3-benzodioxol-4-yl)methylene)hydrazinyl]thiazole (2j) showed antiproliferative activity against K562 cell line with an IC50 value of 8.87±1.93 µM similar to imatinib (IC50= 6.84±1.11 µM). Compound 2j was found to be more effective than imatinib on HL-60, Jurkat and MT-2 cells. Compound 2j also showed cytotoxic activity against HeLa cell line similar to imatinib. The higher selectivity index value of compound 2j than imatinib indicated that its antiproliferative activity was selective. Compound 2j also induced apoptosis in K562 cell line more than imatinib. Among eight TKs, compound 2j showed the strongest inhibitory activity against ABL1 kinase enzyme (IC50= 5.37±1.17 µM). According to molecular docking studies, compound 2j exhibited high affinity to the ATP binding site of ABL1 kinase forming significant intermolecular interactions. On the basis of in silico studies, this compound did not violate Lipinski's rule of five and Jorgensen's rule of three. Conclusion: Compound 2j stands out as a potential orally bioavailable ABL1 kinase inhibitor for the treatment of CML.

scholarly journals In Silico Molecular Docking and Interaction Analysis of Traditional Chinese Medicines Against SARS-CoV-2 Receptor

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110150
Author(s):  
Gang Li ◽  
Wei Zhou ◽  
Xiurong Zhao ◽  
Ying Xie
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Interaction Analysis ◽  
Herbal Remedies ◽  
Receptor Protein ◽  
Stable Complex ◽  
Traditional Chinese Medicines ◽  
Ligand Interaction ◽  
Chinese Medicines ◽  
In Silico Molecular Docking

The novel coronavirus, 2019-nCoV, has led to a major pandemic in 2020 and is responsible for more than 2.9 million officially recorded deaths worldwide. As well as synthetic anti-viral drugs, there is also a need to explore natural herbal remedies. The Traditional Chinese Medicines (TCMs) system has been used for thousands of years for the prevention, diagnosis, and treatment of several chronic diseases. In this paper, we performed an in silico molecular docking and interaction analysis of TCMs against SARS-CoV-2 receptor RNA-dependent RNA polymerase (RdRp). We obtained the 5 most effective plant compounds which had a better binding affinity towards the target receptor protein. These compounds areforsythoside A, rutin, ginkgolide C, icariside II, and nolinospiroside E. The top-ranked compound, based on docking score, was nolinospiroside, a glycoside found in Ophiopogon japonicas that has antioxidant properties. Protein-ligand interaction analysis discerned that nolinospiroside formed a strong bond between ARG 349 of the protein receptor and the carboxylate group of the ligand, forming a stable complex. Hence, nolinospiroside could be deployed as a lead compound against SARS-CoV-2 infection that can be further investigated for its potential benefits in curbing the viral infection.

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