scholarly journals Design, Synthesis and Preliminary Biological Evaluation of Benzylsulfone Coumarin Derivatives as Anti-Cancer Agents

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4034 ◽  
Author(s):  
Tao Wang ◽  
Tao Peng ◽  
Xiaoxue Wen ◽  
Gang Wang ◽  
Yunbo Sun ◽  
...  
Keyword(s):  
Cell Lines ◽  
Docking Study ◽  
Biological Evaluation ◽  
Coumarin Derivatives ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Ic50 Values ◽  
Kinase Inhibitory Activity ◽  
In Silico Molecular Docking

In this work, a series of benzylsulfone coumarin derivatives 5a–5o were synthesized and characterized. Kinase inhibitory activity assay indicated that most of the compounds showed considerable activity against PI3K. Anti-tumor activity studies of the active compounds were also carried out in vitro on the Hela, HepG2, H1299, HCT-116, and MCF-7 tumor cell lines by MTS assay. The structure–activity relationships (SARs) of these compounds were analyzed in detail. Compound 5h exhibited the most potent activities against the mentioned cell lines with IC50 values ranging from 18.12 to 32.60 μM, followed by 5m with IC50 values of 29.30–42.14 μM. Furthermore, 5h and 5m clearly retarded the migration of Hela cells in vitro. Next, an in silico molecular docking study was conducted to evaluate the binding models of 5h and 5m towards PI3Kα and PI3Kβ. Collectively, the above findings suggested that compounds 5h and 5m might be promising PI3K inhibitors deserving further investigation for cancer treatment.

scholarly journals Design, Synthesis, and Biological Evaluation of Pyridineamide Derivatives Containing a 1,2,3-Triazole Fragment as Type II c-Met Inhibitors

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 10 ◽  
Author(s):  
Hehua Xiong ◽  
Jianxin Cheng ◽  
Jianqing Zhang ◽  
Qian Zhang ◽  
Zhen Xiao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Docking Simulation ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Ic50 Values ◽  
Mcf 7

A series of 4-(pyridin-4-yloxy)benzamide derivatives containing a 1,2,3-triazole fragment were designed, synthesized, and their inhibitory activity against A549, HeLa, and MCF-7 cancer cell lines was evaluated. Most compounds exhibited moderate to potent antitumor activity against the three cell lines. Among them, the promising compound B26 showed stronger inhibitory activity than Golvatinib, with IC50 values of 3.22, 4.33, and 5.82 μM against A549, HeLa, and MCF-7 cell lines, respectively. The structure–activity relationships (SARs) demonstrated that the modification of the terminal benzene ring with a single electron-withdrawing substituent (fluorine atom) and the introduction of a pyridine amide chain with a strong hydrophilic group (morpholine) to the hinge region greatly improved the antitumor activity. Meanwhile, the optimal compound B26 showed potent biological activity in some pharmacological experiments in vitro, such as cell morphology study, dose-dependent test, kinase activity assay, and cell cycle experiment. Finally, the molecular docking simulation was performed to further explore the binding mode of compound B26 with c-Met.

Design, Synthesis and invitro biological evaluation of Pyridine,thiadazole, Benzimidazole and Acetyl thiophneAnalogues as Anti tubercular Agents Targeting enzyme InhA

2020 ◽  
Vol 16 ◽  
Author(s):  
Ayyadurai J Suresh ◽  
Sivashankar Nandini ◽  
Krishnanmurthy Sangeetha ◽  
Loganathan S Dhivya ◽  
Parakkot R Surya
Keyword(s):  
Acyl Carrier Protein ◽  
Docking Study ◽  
Biological Evaluation ◽  
Benzimidazole Derivatives ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
H37rv Strain ◽  
Immunodeficiency Virus ◽  
Global Population

Background: Tuberculosis, is a chronic infectious disease, affects one third of the global population. Emergence of Multi-resistant (MDR) strains and high susceptibility of human immunodeficiency virus (HIV) infected persons to the disease forced to develop novel anti-tuberculosis agents and preferably have a novel mechanism of action as to avoid crossresistant with other agents. Literature survey evidences that, Pyridine, Thiadiazole , Benzimidazole; and Acetyl thiophene derivatives exhibit various pharmacological activities, including anti-mycobacterial activity. Methods: Thus, a series of Pyridine, Thiadiazole, Benzimidazole; and Acetyl thiophene based molecules were designed and docked against crucial mtb enzyme target InhA (Enoyl Acyl Carrier Protein Reductase) Enzyme. The docked molecules were screened against good docking-score and multiple interactions and opted for synthesis. Synthesized molecules were re crystallized to obtain the purity. All the purified compounds were characterized by various spectral analyses and evaluated for anti- mycobacterial activity against tuberculosis H37RV strain by Microplate Alamar Blue Assay (MABA) method. Results: The experimental results shown that schiff base of Pyridine (Compounds ‘d’ ) and Benzimidazole derivatives (Compounds ‘i’ ) possesses good anti-tubercular activity with a MIC below 1.6 μg /mL. Further compound ‘e’ of benzimdazole derivative showed good anti tubercular activity with an MIC below 6.25 μg /mL. Whereas 2 - acetyl thiopene compounds exhibited moderate anti tubercular activity at below 50μg/mL. Conclusion: The comparative in vitro and molecular docking study analysis reveals that, compared to chalcones of Acetyl thiophne derivatives, Pyridine, thiadazole and Benzimidazole based schiff bases exhibited best anti tubercular activity.

scholarly journals INDOLE DERIVATIVES: DESIGN, SYNTHESIS, IN-VITRO BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY AS ANTICANCER AGENTS

2018 ◽  
Vol 5 (1) ◽  
pp. 28-32
Author(s):  
Amuthavalli A ◽  
Prakash B ◽  
Velmurugan R
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Docking Study ◽  
Docking Studies ◽  
Biological Evaluation ◽  
In Vitro Cytotoxicity ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Standard Drug

New hetero annulated indoles were synthesized and structurally characterized by spectral means. In order to understand the nature of interactions of these molecules, we carried out molecular docking studies using the protein kinase CK2 inhibitors. The docking results provided some useful information for the futuredesign of more potent inhibitors. The in vitro cytotoxicity was evaluated for all the new compounds by MTT assay against HeLa and compared with the standard drug ellipticine. All the compounds showed moderate to potent activity against the cell lines. The preliminary structure–activity relationships were carried out.

scholarly journals Synthesis, X-ray Analysis, Biological Evaluation and Molecular Docking Study of New Thiazoline Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1654
Author(s):  
Yahia N. Mabkhot ◽  
H. Algarni ◽  
Abdulrhman Alsayari ◽  
Abdullatif Bin Muhsinah ◽  
Nabila A. Kheder ◽  
...  
Keyword(s):  
Cell Lines ◽  
Docking Study ◽  
Biological Evaluation ◽  
Significant Activity ◽  
Inhibition Activity ◽  
Antitumor Activities ◽  
Molecular Docking Study ◽  
X Ray ◽  
Hct 116

A series of new thiazoline derivatives were synthesized. Structure analyses were accomplished employing 1H-NMR, 13C-NMR, X-ray and MS techniques. The in vitro antitumor activities were assessed against human hepatocellular carcinoma (HepG-2) and colorectal carcinoma (HCT-116) cell lines. The results revealed that the thiazolines 5b and 2c exhibited significant activity against the two cell lines. The in vitro antimicrobial screening showed that the thiazolines 2c, 5b and 5d showed promising inhibition activity against Salmonella sp. Additionally, the inhibition activity of thiazolines 2e and 5b against Escherichia coli was comparable to that of the reference compound gentamycin.

scholarly journals Design, Synthesis and Biological Evaluation of 1-Phenyl-2-(phenylamino) Ethanone Derivatives as Novel MCR-1 Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2719 ◽  
Author(s):  
Xiu-juan Lan ◽  
Hai-tao Yan ◽  
Feng Lin ◽  
Shi Hou ◽  
Chen-chen Li ◽  
...  
Keyword(s):  
Docking Study ◽  
Multidrug Resistant ◽  
Biological Evaluation ◽  
Gram Negative Bacteria ◽  
Racemic Compound ◽  
Colistin Resistance ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Synthesis And Biological Evaluation

Polymyxins are considered to be the last-line antibiotics that are used to treat infections caused by multidrug-resistant (MDR) gram-negative bacteria; however, the plasmid-mediated transferable colistin resistance gene (mcr-1) has rendered polymyxins ineffective. Therefore, the protein encoded by mcr-1, MCR-1, could be a target for structure-based design of inhibitors to tackle polymyxins resistance. Here, we identified racemic compound 3 as a potential MCR-1 inhibitor by virtual screening, and 26 compound 3 derivatives were synthesized and evaluated in vitro. In the cell-based assay, compound 6g, 6h, 6i, 6n, 6p, 6q, and 6r displayed more potent activity than compound 3. Notably, 25 μΜ of compound 6p or 6q combined with 2 μg·mL-1 colistin could completely inhibit the growth of BL21(DE3) expressing mcr-1, which exhibited the most potent activity. In the enzymatic assay, we elucidate that 6p and 6q could target the MCR-1 to inhibit the activity of the protein. Additionally, a molecular docking study showed that 6p and 6q could interact with Glu246 and Thr285 via hydrogen bonds and occupy well the cavity of the MCR-1 protein. These results may provide a potential avenue to overcome colistin resistance, and provide some valuable information for further investigation on MCR-1 inhibitors.

scholarly journals Design, Synthesis, and Biological Evaluation of Novel Thienopyrimidine Derivatives as PI3Kα Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3422 ◽  
Author(s):  
Lide Yu ◽  
Qinqin Wang ◽  
Caolin Wang ◽  
Binliang Zhang ◽  
Zunhua Yang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Moderate Activity ◽  
Design Synthesis ◽  
Ic50 Values ◽  
Kinase Inhibitory Activity ◽  
Synthesis And Biological Evaluation

Three series of novel thienopyrimidine derivatives 9a–l, 15a–l, and 18a–h were designed and synthesized, and their IC50 values against four cancer cell lines HepG-2, A549, PC-3, and MCF-7 were evaluated. Most compounds show moderate cytotoxicity against the tested cancer cell lines. The most promising compound 9a showed moderate activity with IC50 values of 12.32 ± 0.96, 11.30 ± 1.19, 14.69 ± 1.32, and 9.80 ± 0.93 µM, respectively. The inhibitory activities of compounds 9a and 15a against PI3Kα and mTOR kinase were further evaluated. Compound 9a exhibited PI3Kα kinase inhibitory activity with IC50 of 9.47 ± 0.63 µM. In addition, docking studies of compounds 9a and 15a were also investigated.

Design, Synthesis and Biological Evaluation: 5-amino-1H-pyrazole-1- carbonyl derivatives as FGFR Inhibitors

2020 ◽  
Vol 17 (11) ◽  
pp. 1330-1341
Author(s):  
Yan Zhang ◽  
Niefang Yu
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Human Gastric Cancer ◽  
Design Synthesis ◽  
Carbonyl Derivatives ◽  
Ic50 Values ◽  
Inhibitory Activities

Background: Fibroblast growth factors (FGFs) and their high affinity receptors (FGFRs) play a major role in cell proliferation, differentiation, migration, and apoptosis. Aberrant FGFR signaling pathway might accelerate development in a broad panel of malignant solid tumors. However, the full application of most existing small molecule FGFR inhibitors has become a challenge due to the potential target mutation. Hence, it has attracted a great deal of attention from both academic and industrial fields for hunting for novel FGFR inhibitors with potent inhibitory activities and high selectivity. Objective: Novel 5-amino-1H-pyrazole-1-carbonyl derivatives were designed, synthesized, and evaluated as FGFR inhibitors. Methods: A series of 5-amino-1H-pyrazole-1-carbonyl derivatives were established by a condensation of the suitable formyl acetonitrile derivatives with either hydrazine or hydrazide derivatives in the presence of anhydrous ethanol or toluene. The inhibitory activities of the target compounds were screened against the FGFRs and two representative cancer cell lines. Tests were carried out to observe the inhibition of 8e against FGFR phosphorylation and downstream signal phosphorylation in human gastric cancer cell lines (SNU-16). The molecular docking of all the compounds were performed using Molecular Operating Environment in order to evaluate their binding abilities with the corresponding protein kinase. Results: A series of 5-amino-1H-pyrazole-1-carbonyl derivatives have been designed and synthesized, screened for their inhibitory activities against FGFRs and cancer cell lines. Most of the target compounds showed moderate to good anti-proliferate activities against the tested enzymes and cell lines. The most promising compounds 8e suppressed FGFR1-3 with IC50 values of 56.4, 35.2, 95.5 nM, and potently inhibited the SNU-16 and MCF-7 cancer cells with IC50 values of 0.71 1.26 μM, respectively. And 8e inhibited the growth of cancer cells containing FGFR activated by multiple mechanisms. In addition, the binding interactions were quite similar in the molecular models between generated compounds and Debio-1347 with the FGFR1. Conclusion: According to the experimental findings, 5-amino-1H-pyrazole-1-carbonyl might serve as a promising template of an FGFR inhibitor.

Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

2020 ◽  
Vol 16 (7) ◽  
pp. 892-902 ◽  
Author(s):  
Aida Iraji ◽  
Mahsima Khoshneviszadeh ◽  
Pegah Bakhshizadeh ◽  
Najmeh Edraki ◽  
Mehdi Khoshneviszadeh
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Docking Study ◽  
Biological Evaluation ◽  
Primary Response ◽  
Ratio Method ◽  
Molecular Docking Study ◽  
Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

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