Iminosugars Spiro-Linked with Morpholine-Fused 1,2,3-Triazole: Synthesis, Conformational Analysis, Glycosidase Inhibitory Activity, Antifungal Assay, and Docking Studies

Background: Phosphatidylinositol-3-kinase α (PI3Kα) is a ubiquitous intracellular enzyme, mainly involved in intracellular signaling pathways, promotes cellular growth, proliferation, and differentiation. Therefore, inhibition of PI3K can be a hotspot in molecular targeted therapy for the treatment of cancer. Methods: The present research work involves molecular docking studies performed to screen derivatives of urea and thiourea bearing thieno [3,2-d]-pyrimidines against the active site of PI3K enzyme using MOE.2008.10. The designed structures (6a-f) and (7a-j) were synthesized by the facile synthetic methods and evaluated for their anticancer activity against HT-29 and MCF-7 cell lines and inhibitory activity against PI3Kα enzyme. Results: Among the tested compounds, 4-(4-(2-(3-(pyrimidin-2-yl)thioureido)ethyl)piperazin-1-yl)thieno[3,2- d]pyrimidine-6-carboxamide (7f) showed the highest anticancer activity against HT-29 and MCF-7 cell lines with IC50 values of 2.18 µM and 4.25 µM, respectively. Further, the same compound also exhibited potent PI3Kα inhibitory activity with IC50 value of 1.26 µM. Conclusion: Docking studies supported the initial pharmacophoric hypothesis and suggested a mode of interaction at the active binding site of PI3Kα, demonstrating that the target compounds were potential inhibitory agents for cancer therapy.

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A New CDK2 Inhibitor with 3-Hydrazonoindolin-2-One Scaffold Endowed with Anti-Breast Cancer Activity: Design, Synthesis, Biological Evaluation, and In Silico Insights

Molecules ◽

10.3390/molecules26020412 ◽

2021 ◽

Vol 26 (2) ◽

pp. 412

Author(s):

Mohammad M. Al-Sanea ◽

Ahmad J. Obaidullah ◽

Mohamed E. Shaker ◽

Garri Chilingaryan ◽

Mohammed M. Alanazi ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Line ◽

Inhibitory Activity ◽

Flow Cytometric Analysis ◽

Docking Studies ◽

Biological Evaluation ◽

Intrinsic Activity ◽

Binding Interaction ◽

Mcf 7

Background: Cyclin-dependent kinases (CDKs) regulate mammalian cell cycle progression and RNA transcription. Based on the structural analysis of previously reported CDK2 inhibitors, a new compound with 3-hydrazonoindolin-2-one scaffold (HI 5) was well designed, synthesized, and biologically evaluated as a promising anti-breast cancer hit compound. Methods: The potential anti-cancerous effect of HI 5 was evaluated using cytotoxicity assay, flow cytometric analysis of apoptosis and cell cycle distribution, ELISA immunoassay, in vitro CDK2/cyclin A2 activity, and molecular operating environment (MOE) virtual docking studies. Results: The results revealed that HI 5 exhibits pronounced CDK2 inhibitory activity and cytotoxicity in human breast cancer MCF-7 cell line. The cytotoxicity of HI 5 was found to be intrinsically mediated apoptosis, which in turn, is associated with low Bcl-2 expression and high activation of caspase 3 and p53. Besides, HI 5 blocked the proliferation of the MCF-7 cell line and arrested the cell cycle at the G2/M phase. The docking studies did not confirm which one of geometric isomers (syn and anti) is responsible for binding affinity and intrinsic activity of HI 5. However, the molecular dynamic studies have confirmed that the syn-isomer has more favorable binding interaction and thus is responsible for CDK2 inhibitory activity. Discussion: These findings displayed a substantial basis of synthesizing further derivatives based on the 3-hydrazonoindolin-2-one scaffold for favorable targeting of breast cancer.

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Conformational analysis, X-ray crystallographic, FT-IR, FT-Raman, DFT, MEP and molecular docking studies on 1-(1-(3-methoxyphenyl) ethylidene) thiosemicarbazide

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy ◽

10.1016/j.saa.2014.12.026 ◽

2015 ◽

Vol 139 ◽

pp. 321-328 ◽

Cited By ~ 8

Author(s):

R.R. Saravanan ◽

S. Seshadri ◽

S. Gunasekaran ◽

R. Mendoza-Meroño ◽

S. Garcia-Granda

Keyword(s):

Molecular Docking ◽

Conformational Analysis ◽

Docking Studies ◽

X Ray ◽

Molecular Docking Studies ◽

Ft Ir ◽

Ft Raman

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Design, synthesis, cytotoxicity, HuTopoIIα inhibitory activity and molecular docking studies of pyrazole derivatives as potential anticancer agents

Bioorganic Chemistry ◽

10.1016/j.bioorg.2016.10.001 ◽

2016 ◽

Vol 69 ◽

pp. 77-90 ◽

Cited By ~ 21

Author(s):

Raquib Alam ◽

Divya Wahi ◽

Raja Singh ◽

Devapriya Sinha ◽

Vibha Tandon ◽

...

Keyword(s):

Molecular Docking ◽

Anticancer Agents ◽

Inhibitory Activity ◽

Docking Studies ◽

Pyrazole Derivatives ◽

Design Synthesis ◽

Molecular Docking Studies

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MOLECULAR DOCKING STUDIES OF CYCLOOXYGENASE ENZYME (COX-2) INHIBITORY ACTIVITY OF MAIN ACTIVE CONSTITUENTS OF CALENDULA OFFICINALIS

International Journal of Research in Ayurveda and Pharmacy ◽

10.7897/2277-4343.100118 ◽

2019 ◽

Vol 10 (1) ◽

pp. 75-79

Author(s):

Anurag Agrawal ◽

Vibhu Jha ◽

Subodh Kumar Dubey ◽

Giriraj T Kulkarni

Keyword(s):

Molecular Docking ◽

Inhibitory Activity ◽

Docking Studies ◽

Calendula Officinalis ◽

Active Constituents ◽

Molecular Docking Studies ◽

Cox 2

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Chemometric Modeling of Structurally Diverse Carbamates for the Inhibition of Acetylcholinesterase (AChE) Enzyme in Alzheimer's Disease

International Journal of Quantitative Structure-Property Relationships ◽

10.4018/ijqspr.2020070102 ◽

2020 ◽

Vol 5 (3) ◽

pp. 6-60 ◽

Cited By ~ 1

Author(s):

Vinay Kumar ◽

Achintya Saha

Keyword(s):

Inhibitory Activity ◽

Enzyme Inhibitors ◽

Quantitative Structure Activity Relationship ◽

Structural Features ◽

Pharmacophore Modeling ◽

Docking Studies ◽

2D Qsar ◽

Validation Parameters ◽

Acetylcholinesterase Enzyme ◽

Pharmacophore Models

In this research, we have developed two-dimensional quantitative structure-activity relationship (2D-QSAR) and group-based QSAR (GQSAR) models employing a dataset of 78 carbamate derivatives (acetylcholinesterase enzyme inhibitors). The developed models were validated using various stringent validation parameters. From the insights obtained from the developed 2D-QSAR and GQSAR models, we have found that the structural features appearing in the models are responsible for the enhancement of the inhibitory activity against the AChE enzyme. Furthermore, we have performed the pharmacophore modeling to unveil the structural requirements for the inhibitory activity. Additionally, molecular docking studies were performed to understand the molecular interactions involved in binding, and the results are then correlated with the requisite structural features obtained from the QSAR and pharmacophore models.

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Conformational analysis and quantum descriptors of two new imidazole derivatives by experimental, DFT, AIM, molecular docking studies and adsorption activity on graphene

Heliyon ◽

10.1016/j.heliyon.2020.e05182 ◽

2020 ◽

Vol 6 (10) ◽

pp. e05182

Author(s):

Veena S. Kumar ◽

Y. Sheena Mary ◽

Kiran Pradhan ◽

Dhiraj Brahman ◽

Y. Shyma Mary ◽

...

Keyword(s):

Molecular Docking ◽

Conformational Analysis ◽

Docking Studies ◽

Adsorption Activity ◽

Molecular Docking Studies ◽

Imidazole Derivatives

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Crystal structure and molecular docking studies of new pyrazole-4-carboxamides

Heterocyclic Communications ◽

10.1515/hc-2019-0012 ◽

2019 ◽

Vol 25 (1) ◽

pp. 66-72 ◽

Cited By ~ 2

Author(s):

Li Qiao ◽

Peng-Peng Cai ◽

Zhong-Hua Shen ◽

Hong-Ke Wu ◽

Cheng-Xia Tan ◽

...

Keyword(s):

Crystal Structure ◽

Molecular Docking ◽

Botrytis Cinerea ◽

Inhibitory Activity ◽

Docking Studies ◽

Active Group ◽

X Ray Diffraction ◽

X Ray ◽

Molecular Docking Studies ◽

H Nmr

AbstractTwo pyrazol-4-carboxamides, 3-(difluoromethyl)-N-(mesitylcarbamoyl)-1-methyl-1H-pyrazole-4-carboxa-mide (7a) and 3-(difluoromethyl)-N-((3,5-dimethylphenyl) carbamoyl)-1-methyl-1H-pyrazole-4-carboxamide (7b) were synthesized and their structures were confirmed by the aid of 1H NMR and HRMS analyses. The structure of the pyrazole-4-carboxamide, 7a was also determined by X-ray diffraction. The preliminary activity results demonstrate that these two compounds exhibit good inhibitory activity against Botrytis cinerea. Further docking results indicated that the key active group is difluoromethyl pyrazole moiety.

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