Design, synthesis, biological evaluation and docking studies of sulfonyl isatin derivatives as monoamine oxidase and caspase-3 inhibitors

MedChemComm ◽  
2016 ◽  
Vol 7 (8) ◽  
pp. 1628-1639 ◽  
Author(s):  
Mohsen Tavari ◽  
Sarel F. Malan ◽  
Jacques Joubert
Keyword(s):  
Monoamine Oxidase ◽  
Caspase 3 ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Multifunctional Agents ◽  
Inhibitory Activities ◽  
Isatin Derivatives ◽  
Micromolar Range

Sulfonyl isatin derivatives as multifunctional agents showing monoamine oxidase and caspase-3 inhibitory activities in the low micromolar range.

Design, Synthesis and Biological Evaluation of Anti-tuberculosis Agents based on Bedaquiline Structure

2020 ◽  
Vol 16 (5) ◽  
pp. 703-714
Author(s):  
Chengjun Wu ◽  
Jinghan Luo ◽  
Mengtong Wu ◽  
Fanzhen Meng ◽  
Zhiqiang Cai ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Atp Synthase ◽  
Docking Study ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Mycobacterium Tuberculosis H37rv ◽  
Inhibitory Activities ◽  
Relationship Of

Background: Bedaquiline is a novel anti-tuberculosis drug that inhibits Mycobacterial ATP synthase. However, studies have found that bedaquiline has serious side effects due to high lipophilicity. Recently, the complete structure of ATP synthase was first reported in the Journal of Science. Objective: The study aimed to design, synthesise and carry out biological evaluation of antituberculosis agents based on the structure of bedaquiline. Methods: The mode of action of bedaquiline and ATP synthase was determined by molecular docking, and a series of low lipophilic bedaquiline derivatives were synthesized. The inhibitory activities of bedaquiline derivatives towards Mycobacterium phlei 1180 and Mycobacterium tuberculosis H37Rv were evaluated in vitro. A docking study was carried out to elucidate the structureactivity relationship of the obtained compounds. The predicted ADMET properties of the synthesized compounds were also analyzed. Results: The compounds 5c3, 6a1, and 6d3 showed good inhibitory activities (MIC=15.62 ug.mL-1). At the same time, the compounds 5c3, 6a1, and 6d3 also showed good drug-like properties through molecular docking and ADMET properties prediction. Conclusion: The results of in vitro anti-tuberculosis activity assays, docking studies and ADMET predictions indicate that the synthesized compounds have potential antifungal activity, with compounds 6a1 being further optimized and developed as lead compounds.

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.

Hybridized Quinoline Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and Molecular Docking

2019 ◽  
Vol 19 (4) ◽  
pp. 439-452 ◽  
Author(s):  
Mohamed R. Selim ◽  
Medhat A. Zahran ◽  
Amany Belal ◽  
Moustafa S. Abusaif ◽  
Said A. Shedid ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Anticancer Agents ◽  
Caspase 3 ◽  
Biological Evaluation ◽  
Tubulin Polymerization ◽  
Design Synthesis ◽  
Chemical Structures ◽  
M Phase ◽  
Induced Apoptosis ◽  
Derivatives Of

Objective: Conjugating quinolones with different bioactive pharmacophores to obtain potent anticancer active agents. Methods: Fused pyrazolopyrimidoquinolines 3a-d, Schiff bases 5, 6a-e, two hybridized systems: pyrazolochromenquinoline 7 and pyrazolothiazolidinquinoline 8, different substituted thiazoloquinolines 13-15 and thiazolo[3,2-a]pyridine derivatives 16a-c were synthesized. Their chemical structures were characterized through spectral and elemental analysis, cytotoxic activity on five cancer cell lines, caspase-3 activation, tubulin polymerization inhibition and cell cycle analysis were evaluated. Results: Four compounds 3b, 3d, 8 and 13 showed potent activity than doxorubicin on HCT116 and three compounds 3b, 3d and 8 on HEPG2. These promising derivatives showed increase in the level of caspase-3. The trifloromethylphenyl derivatives of pyrazolopyrimidoquinolines 3b and 3d showed considerable tubulin polymerization inhibitory activity. Both compounds arrested cell cycle at G2/M phase and induced apoptosis. Conclusion: Compounds 3b and 3d can be considered as promising anticancer active agents with 70% of colchicine activity on tubulin polymerization inhibition and represent hopeful leads that deserve further investigation and optimization.

scholarly journals Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4718
Author(s):  
Lamya H. Al-Wahaibi ◽  
Bahaa G. M. Youssif ◽  
Ehab S. Taher ◽  
Ahmed H. Abdelazeem ◽  
Antar A. Abdelhamid ◽  
...  
Keyword(s):  
Proliferative Activity ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Selectivity Ratio ◽  
Computational Studies ◽  
Design Synthesis ◽  
Ca Ix ◽  
Side Pocket ◽  
Modelling Simulation ◽  
Good Agreement

A novel series of tri-aryl imidazole derivatives 5a–n carrying benzene sulfonamide moiety has been designed for their selective inhibitory against hCA IX and XII activity. Six compounds were found to be potent and selective CA IX inhibitors with the order of 5g > 5b > 5d > 5e > 5g > 5n (Ki = 0.3–1.3 μM, and selectivity ratio for hCA IX over hCA XII = 5–12) relative to acetazolamide (Ki = 0.03 μM, and selectivity ratio for hCA IX over hCA XII = 0.20). The previous sixth inhibitors have been further investigated for their anti-proliferative activity against four different cancer cell lines using MTT assay. Compounds 5g and 5b demonstrated higher antiproliferative activity than other tested compounds (with GI50 = 2.3 and 2.8 M, respectively) in comparison to doxorubicin (GI50 = 1.1 M). Docking studies of these two compounds adopted orientation and binding interactions with a higher liability to enter the active side pocket CA-IX selectively similar to that of ligand 9FK. Molecular modelling simulation showed good agreement with the acquired biological evaluation.

scholarly journals N,N′-Disubstituted thiourea and urea derivatives: design, synthesis, docking studies and biological evaluation against nitric oxide synthase

MedChemComm ◽  
2016 ◽  
Vol 7 (4) ◽  
pp. 667-678 ◽  
Author(s):  
Mariem Chayah ◽  
M. Encarnación Camacho ◽  
M. Dora Carrión ◽  
Miguel A. Gallo ◽  
Miguel Romero ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Urea Derivatives ◽  
Design Synthesis ◽  
Inos Inhibitors ◽  
Oxide Synthase

N,N′-Disubstituted thioureas and ureas as nNOS and iNOS inhibitors were synthesized. Thiourea 4g was the best inhibitor without eNOS inhibition.

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