Design of dual MMP-2/HDAC-8 inhibitors by pharmacophore mapping, molecular docking, synthesis and biological activity

RSC Advances ◽  
2015 ◽  
Vol 5 (88) ◽  
pp. 72373-72386 ◽  
Author(s):  
Amit K. Halder ◽  
Sumana Mallick ◽  
Deep Shikha ◽  
Achintya Saha ◽  
Krishna D. Saha ◽  
...  
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Migration And Invasion ◽  
Pharmacophore Mapping ◽  
Cancer Migration

Recent analyses have highlighted the promotion of cancer migration and invasion, mediated through HDAC via MMP-2 and MMP-9.

Development of Structure Activity Correlation Model on Aroylindole Derivatives as Anticancer Agents

2018 ◽  
Vol 15 (2) ◽  
pp. 143-153
Author(s):  
Vijay K. Patel ◽  
Harish Rajak
Keyword(s):  
Hydrogen Bond ◽  
Biological Activity ◽  
Molecular Docking ◽  
Covalent Binding ◽  
Research Work ◽  
3D Qsar ◽  
Pharmacophore Mapping ◽  
Hydrogen Bond Acceptor ◽  
Computational Approaches ◽  
Structure Activity

Background: Aroylindole derivatives, the structural analogs of Combretastatin A-4 has been found to possess potent growth inhibitory activity on several cancer cell lines due to its excellent antitumor and antivascular activities. The aim of present research work is to identify lead and establish structure activity correlation of trimethoxyaroylindole derivatives, using integrated ligand and structure based computational approaches. Materials and Methods: A correlation between structure and biological activity was established using computational approaches i.e., structure activity correlation by pharmacophore and atom based 3D QSAR, molecular docking and energetic based pharmacophore mapping studies of trimethoxyaroylindole derivatives. Results and Discussion: The 3D-QSAR on trimethoxyaroylindole derivatives generated and showed best statistical result for CPHs AAARR.182 was validated by Q2 (0.6929), R2 (0.82). The Comp. 1 of the training set was employed as template for hydrogen bond donor, hydrophobic and hydrogen bond acceptor field prediction features and visualization of the 3D-QSAR model provides details of relationship between structure and biological activity of trimethoxyaroylindole derivatives. Pharmacophore model was developed by Phase and e-pharmacophore on comp. 1, the trimethoxy group with ring A, keto group, N-H group with ring B and ring C are pharmacophoric group important for the lead generation and coincide with various chemical features that may facilitate non-covalent binding between the ligand and its target receptor. Molecular docking studies showed critical interactions between Cys241, Val318 and meta, para-methoxy group at ring A while and Thr179 and NH of indole (distance 3.5 Å). The para position of trimethoxyphenyl ring bind to SH group of CYS 241 receptor molecule via hydrogen bond. Conclusion: The lead identification and establish structure activity correlation of trimethoxyaroylindole derivatives, were performed using integrated ligand and structure based computational approaches i.e., atom based 3D QSAR and pharmacophore study, molecular docking, energetic based pharmacophore mapping studies showed promising results. The outcomes of present studies could be utilized for the design of novel aroylindole derivatives including its lead optimization as potential anticancer agent.

Quantitative structure-activity relationship model, molecular docking simulation and computational design of some novel compounds against DNA gyrase receptor.

2020 ◽  
Vol 16 ◽  
Author(s):  
Shola Elijah Adeniji
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Binding Energy ◽  
Biological Activities ◽  
Docking Simulation ◽  
Dna Gyrase ◽  
Computational Design ◽  
Multi Drug Resistance ◽  
Drug Candidate ◽  
Standard Drug

Introduction: Mycobacterium tuberculosis has instigated a serious challenge toward the effective treatment of tuberculosis. The reoccurrence of the resistant strains of the disease to accessible drugs/medications has mandate for the development of more effective anti-tubercular agents with efficient activities. Time expended and costs in discovering and synthesizing new hypothetical drugs with improved biological activity have been a major challenge toward the treatment of multi-drug resistance strain M. tuberculosis (TB). Meanwhile, to solve the problem stated, a new approach i.e. QSAR which establish connection between novel drugs with a better biological against M. tuberculosis is adopted. Methods: The anti-tubercular model established in this study to forecast the biological activities of some anti-tubercular compounds selected and to design new hypothetical drugs is subjective to the molecular descriptors; MATS7s, SM1_DzZ, SpMin4_Bhv, TDB3v and RDF70v. Ligand-receptor interactions between quinoline derivatives and the receptor (DNA gyrase) was carried out using molecular docking technique by employing the PyRx virtual screening software and discovery studio visualizer software. Furthermore, docking study indicates that compounds 20 of the derivatives with promising biological activity have the utmost binding energy of -17.79 kcal/mol. Results: Meanwhile, the interaction of the standard drug; isoniazid with the target enzyme was observed with the binding energy -14.6 kcal/mol which was significantly lesser than the binding energy of the ligand (compound 20).Therefore, compound 20 served as a template structure to designed compounds with more efficient activities. Among the compounds designed; compounds 20p was observed with better anti-tubercular activities with more prominent binding affinities of -24.3kcal/mol. Conclusion: The presumption of this research aid the medicinal chemists and pharmacist to design and synthesis a novel drug candidate against the tuberculosis. Moreover, in-vitro and in-vivo test could be carried out to validate the computational results.

scholarly journals New Mononuclear and Binuclear Cu(II), Co(II), Ni(II), and Zn(II) Thiosemicarbazone Complexes with Potential Biological Activity: Antimicrobial and Molecular Docking Study

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2288
Author(s):  
Ahmed Gaber ◽  
Moamen S. Refat ◽  
Arafa A.M. Belal ◽  
Ibrahim M. El-Deen ◽  
Nader Hassan ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Biological Activity ◽  
Molecular Docking ◽  
Metal Complexes ◽  
Analytical Data ◽  
Docking Study ◽  
Spectroscopic Techniques ◽  
Molecular Docking Study ◽  
Tetrahedral Geometry ◽  
Thiosemicarbazone Complexes

Herein, we report the synthesis of eight new mononuclear and binuclear Co2+, Ni2+, Cu2+, and Zn2+ methoxy thiosemicarbazone (MTSC) complexes aiming at obtaining thiosemicarbazone complex with potent biological activity. The structure of the MTSC ligand and its metal complexes was fully characterized by elemental analysis, spectroscopic techniques (NMR, FTIR, UV-Vis), molar conductivity, thermogravimetric analysis (TG), and thermal differential analysis (DrTGA). The spectral and analytical data revealed that the obtained thiosemicarbazone-metal complexes have octahedral geometry around the metal center, except for the Zn2+-thiosemicarbazone complexes, which showed a tetrahedral geometry. The antibacterial and antifungal activities of the MTSC ligand and its (Co2+, Ni2+, Cu2+, and Zn2+) metal complexes were also investigated. Interestingly, the antibacterial activity of MTSC- metal complexes against examined bacteria was higher than that of the MTSC alone, which indicates that metal complexation improved the antibacterial activity of the parent ligand. Among different metal complexes, the MTSC- mono- and binuclear Cu2+ complexes showed significant antibacterial activity against Bacillus subtilis and Proteus vulgaris, better than that of the standard gentamycin drug. The in silico molecular docking study has revealed that the MTSC ligand could be a potential inhibitor for the oxidoreductase protein.

Structural, QSAR, machine learning and molecular docking studies of 5-thiophen-2-yl pyrazole derivatives as potent and selective cannabinoid-1 receptor antagonists

2021 ◽  
Author(s):  
Riad Hanachi ◽  
Ridha Ben Said ◽  
Hamza Allal ◽  
Seyfeddine Rahali ◽  
Mohammed A. M. Alkhalifah ◽  
...  
Keyword(s):  
Machine Learning ◽  
Biological Activity ◽  
Molecular Docking ◽  
Theoretical Analysis ◽  
Structural Study ◽  
Docking Studies ◽  
Pyrazole Derivatives ◽  
Molecular Docking Studies ◽  
Cannabinoid 1 Receptor ◽  
Chemical Descriptors

We performed a structural study followed by a theoretical analysis of the chemical descriptors and the biological activity of a series of 5-thiophen-2-yl pyrazole derivatives as potent and selective Cannabinoid-1...

Synthesis, molecular docking, and biological activity of thioether derived from juglone in preclinical models of chronic myeloid leukemia

2021 ◽  
pp. 100197
Author(s):  
Adrhyann J. de S. Portilho ◽  
Carinne B.S.M.R. Gomes ◽  
Caroline S. Moreira ◽  
Luana da S.M. Forezi ◽  
Pâmella S. Cordeiro ◽  
...  
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Preclinical Models

scholarly journals An Unconditional Positivity-Preserving Difference Scheme for Models of Cancer Migration and Invasion

Mathematics ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 131
Author(s):  
Mikhail K. Kolev ◽  
Miglena N. Koleva ◽  
Lubin G. Vulkov
Keyword(s):  
Difference Scheme ◽  
Nonlinear Parabolic Equations ◽  
Nonlinear Ordinary Differential Equation ◽  
Diffusion Reaction ◽  
Migration And Invasion ◽  
Reaction Type ◽  
Truncation Errors ◽  
Cancer Migration ◽  
Nonlinear Parabolic ◽  
Unconditional Positivity

In this paper, we consider models of cancer migration and invasion, which consist of two nonlinear parabolic equations (one of the convection–diffusion reaction type and the other of the diffusion–reaction type) and an additional nonlinear ordinary differential equation. The unknowns represent concentrations or densities that cannot be negative. Widely used approximations, such as difference schemes, can produce negative solutions because of truncation errors and can become unstable. We propose a new difference scheme that guarantees the positivity of the numerical solution for arbitrary mesh step sizes. It has explicit and fast performance even for nonlinear reaction terms that consist of sums of positive and negative functions. The numerical examples illustrate the simplicity and efficiency of the method. A numerical simulation of a model of cancer migration is also discussed.

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