scholarly journals Kinase Inhibitory Activities and Molecular Docking of a Novel Series of Anticancer Pyrazole Derivatives

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3074 ◽  
Author(s):  
Eman Nossier ◽  
Somaia Abd El-Karim ◽  
Nagy Khalifa ◽  
Ali El-Sayed ◽  
Emad Hassan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Simulation ◽  
Braf V600e ◽  
Kinase Assay ◽  
Assay Method ◽  
Molecular Docking Simulation ◽  
Hct 116 ◽  
Mcf 7

A series of novel 1,3,4-triarylpyrazoles containing different heterocycles has been prepared, characterized and screened for their in vitro antiproliferative activity against HePG-2, MCF-7, PC-3, A-549 and HCT-116 cancer cell lines. The biological results revealed that compound 6 showed the highest anticancer activity so it was subjected to a kinase assay study where it reduced the activity of several protein kinases including AKT1, AKT2, BRAF V600E, EGFR, p38α and PDGFRβ at 100 μM using the radiometric or ADP-Glo assay method. Molecular docking simulation supported the initial kinase assay and suggested a common mode of interaction at the ATP-binding sites of these kinases, which demonstrates that compound 6 is a potential agent for cancer therapy deserving further research.

Design, Molecular docking, Synthesis and Biological evaluation of 5, 7 dimethyl pyrido(2, 3-d)pyrimidin-4-one and 4,5 dihydro pyrazolo (3, 4-d) pyrimidines for cytotoxic activity

2021 ◽  
pp. 3029-3038
Author(s):  
M. Sathish Kumar ◽  
M. Vijey Aanandhi
Keyword(s):  
Molecular Docking ◽  
Docking Simulation ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Hep G2 ◽  
Molecular Docking Simulation ◽  
Hela Cell Lines ◽  
Benzene Diazonium ◽  
Synthesis And Biological Evaluation ◽  
Mcf 7

The fused pyrimidine derivatives are potent tyrosine kinase and thymidylate synthase inhibitors. The compound 3-(4-sulphonyl amino)-2-methyl thio-6-phenyl azo-5, 7-dimethyl pyrido(2,3-d)pyrimidin-4-one was synthesized from Ethyl 2-amino-4,6-dimethylpyridine-3-carboxylate, benzene diazonium chloride, benzene sulphonyl amino isothiocyanate in subsequent reactions. 1-(1, 3-benzothiazol-2-yl)-3-methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidines were synthesized from 1, 3-benzothiazole, 2-thiol, Hydrazine Hydrate, 2-hydrazinyl-1, 3-benzothiazole and aldehydes in subsequent reactions. Twenty-five derivatives pyrimidine scaffolds were designed and performed molecular docking studies for the ability to inhibit the target protein using molecular docking simulation, selective compounds were synthesized and characterized by spectral methods. All the synthesized compounds evaluated for their antioxidant activity and MTT assay exhibited compounds 13c, 13e and 14d can be potential anticancer candidates against MCF-7, Hep G2 and Hela cell lines respectively. Based on all the studies conclude that good agreement was observed between the top-ranked docking scores and top experimental inhibitors when compared with standards ascorbic acid and imatinib. Hence, the compounds could be considered as new anticancer hits for further lead optimization.

Binding Investigation of Integrin αvβ3 With Its Inhibitors by SPR Technology and Molecular Docking Simulation

2010 ◽  
Vol 15 (2) ◽  
pp. 131-137 ◽  
Author(s):  
Yaqin Liu ◽  
Yuanjiang Pan ◽  
Yuhong Xu
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Structural Model ◽  
Docking Simulation ◽  
Integrin Αvβ3 ◽  
Equilibrium Dissociation Constant ◽  
Molecular Docking Simulation ◽  
Spr Biosensor ◽  
Inhibitor Discovery ◽  
Equilibrium Dissociation

Integrins play critical roles in the process of angiogenesis and are attractive targets for anticancer therapies. It is desirable to develop new types of small-molecule inhibitors of integrin. Herein, the binding features of several inhibitors to integrin αvβ3 have been studied by surface plasmon resonance (SPR) biosensor technology and molecular docking analyses. The SPR results indicated that the equilibrium dissociation constant (KD) values are evaluated for the inhibitors and showed that the KD value of cyclopeptide c-Lys is much lower than the reference molecule. In addition, the 3D structural model of integrin αvβ3 was generated according to the crystal structure of the integrin αvβ3 complex, and the molecular docking simulation analyses revealed that the predicted binding sites for the most active cyclopeptide c-Lys were consistent with the reported structure. These results thus implied that cyclopeptide c-Lys could be developed as a novel inhibitor for integrin αvβ3. The current work has potential for application in structure-based integrin αvβ3 inhibitor discovery.

Molecular docking simulation and in vitro studies on estrogenic activities of flavonoids from leaves of Carya cathayensis Sarg

Steroids ◽  
2020 ◽  
Vol 163 ◽  
pp. 108726
Author(s):  
Jing-Jing Lu ◽  
Fang-Mei Zhou ◽  
Xu-Jiao Hu ◽  
Jing-Jing Fang ◽  
Cai-Xia Liu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Simulation ◽  
In Vitro Studies ◽  
Molecular Docking Simulation ◽  
Carya Cathayensis ◽  
Carya Cathayensis Sarg

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

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.

scholarly journals Development of Novel Quinoline-Based Sulfonamides as Selective Cancer-Associated Carbonic Anhydrase Isoform IX Inhibitors

2021 ◽  
Vol 22 (20) ◽  
pp. 11119
Author(s):  
Moataz Shaldam ◽  
Alessio Nocentini ◽  
Zainab M. Elsayed ◽  
Tamer M. Ibrahim ◽  
Rofaida Salem ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Carbonic Anhydrase ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Inhibitory Action ◽  
Docking Simulation ◽  
Simulation Studies ◽  
Molecular Docking Simulation ◽  
Anchoring Group ◽  
Mcf 7

A new series of quinoline-based benzenesulfonamides (QBS) were developed as potential carbonic anhydrase inhibitors (CAIs). The target QBS CAIs is based on the 4-anilinoquinoline scaffold where the primary sulphonamide functionality was grafted at C4 of the anilino moiety as a zinc anchoring group (QBS 13a–c); thereafter, the sulphonamide group was switched to ortho- and meta-positions to afford regioisomers 9a–d and 11a–g. Moreover, a linker elongation approach was adopted where the amino linker was replaced by a hydrazide one to afford QBS 16. All the described QBS have been synthesized and investigated for their CA inhibitory action against hCA I, II, IX and XII. In general, para-sulphonamide derivatives 13a–c displayed the best inhibitory activity against both cancer-related isoforms hCA IX (KIs = 25.8, 5.5 and 18.6 nM, respectively) and hCA XII (KIs = 9.8, 13.2 and 8.7 nM, respectively), beside the excellent hCA IX inhibitory activity exerted by meta-sulphonamide derivative 11c (KI = 8.4 nM). The most promising QBS were further evaluated for their anticancer and pro-apoptotic activities on two cancer cell lines (MDA-MB-231 and MCF-7). In addition, molecular docking simulation studies were applied to justify the acquired CA inhibitory action of the target QBS.

scholarly journals Synthesis, Antiproliferative Activity and Molecular Docking Studies of 1,3,5-Triaryl Pyrazole Compound as Estrogen α Receptor Inhibitor Targeting MCF-7 Cells Line

Molekul ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 18
Author(s):  
Noval Herfindo ◽  
Riska Prasetiawati ◽  
Daniel Sialagan ◽  
Neni Frimayanti ◽  
Adel Zamri
Keyword(s):  
Molecular Docking ◽  
Antiproliferative Activity ◽  
Docking Simulation ◽  
Docking Studies ◽  
Biological Evaluation ◽  
One Pot ◽  
Vitro Assay ◽  
Oxidative Aromatization ◽  
Mcf 7

This research has been successfully synthesized three compounds of 1,3,5-triaryl pyrazole derivatives by two steps reaction. Firstly, pyrazoline (4a-c) compound was obtained by one-pot reaction of aromatic ketones, aldehyde and hydrazine in basic condition. Then, pyrazole (5a-c) compound was obtained by oxidative aromatization of compound 4 in the presense of acetic acid. Chemical structure of predicted molecules was confirmed by FTIR, NMR and HRMS spectroscopy data analysis. Antiproliferative activity of compound 5a-c were evaluated by in vitro assay against MCF-7 cells line and molecular docking simulation against ERα (PDB ID: 3ERT) using MOE 2019. Biological evaluation result showed that pyrazole compounds had weak antiproliferative activity against MCF-7 cells with IC50 were > 1000 µM, whereas the docking studies agrees the result.

scholarly journals Anticancer and molecular docking studies of some new pyrazole-1-carbothioamide nucleosides

2019 ◽  
Vol 9 (6) ◽  
pp. 4642-4648 ◽  
Keyword(s):  
Molecular Docking ◽  
Human Cancer ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Reference Drug ◽  
Human Cancer Cell Lines ◽  
Chemical Structures ◽  
Hct 116 ◽  
Mcf 7

Eight pyrazole-1-carbothioamide nucleosides were synthesized through conensation of 3-(4-aminophenyl)-pyrazole-1-carbothioamide derivative 2 with four aldoses (arabinose, mannose, glucose and galactose) and acetylation of the produced nucleosides 3a-d with acetic anhydride in pyridine at room temperature to give their corresponding acetyl derivatives 4a-d. Their chemical structures were confirmed by spectroscopic and elemental analysis. The antiproliferative activity was screened against various human cancer cell lines (MCF-7, HepG2 and HCT-116) in vitro; compound 4b showed a significant IC50 values (8.5±0.72 for MCF-7, 9.4±0.84 for HepG2 and 11.7±0.89 µg/ml for HCT-116) which were close to the reference drug 5-fluorouracil (5-FU). Molecular docking study was utilized to illustrate the ability of the more active compounds 3b and 4b to inhibit thymidylate synthase and compare the results with an antimetabolite drug used in cancer chemotherapy "Raltitrexed".

scholarly journals Evaluation of the Inhibitory Activities of Ferula gummosa Bioactive Compounds against the Druggable Targets of SARS-CoV-2: Molecular Docking Simulation

2021 ◽  
Vol 12 (5) ◽  
pp. 6382-6392
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Simulation ◽  
Large Family ◽  
Viral Disease ◽  
Valuable Resource ◽  
Molecular Docking Simulation ◽  
Natural Components ◽  
Inhibitory Activities ◽  
Druggable Targets

SARS-CoV-2, an infectious disease caused by a novel strain that belongs to a large family of coronaviruses, has emerged as a global health threat. This viral disease affects the epithelial cells of the respiratory system and eventually leads to pneumonia. Using medicine derived from natural and safe herbs could be an alternative way of preventing or even treating severe respiratory disorders. This research has been conducted to evaluate the anti-inflammatory potential of Ferula gummosa Boiss. in preventing Covid-19. Molecular docking simulation was performed on the 18 components of Ferula gummosa against known active binding sites of SARS-CoV-2. The results revealed that these compounds inhibited the vital proteins of SARS-CoV-2, including 6LU7, 6EX1, 6W9C, and 6M71. According to the docking scores (DS) and inhibition constants (Ki), the most potent anti-coronavirus activity is expressed in the order: Δ-Cadinen > β-eudesmol > Bulnesol. The docking results revealed that the natural components of Ferula gummosa, mainly Δ-Cadinene, could be considered a valuable resource for preventing the infection of SARS-CoV-2.

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