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Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancer.
- Source :
-
Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] 2022 Dec; Vol. 37 (1), pp. 39-50. - Publication Year :
- 2022
-
Abstract
- In this work, the natural piperine moiety was utilised to develop two sets of piperine-based amides ( 5a-i ) and ureas ( 8a-y ) as potential anticancer agents. The anticancer action was assessed against triple negative breast cancer (TNBC) MDA-MB-231, ovarian A2780CP and hepatocellular HepG2 cancer cell lines. In particular, 8q stood out as the most potent anti-proliferative analogue against TNBC MDA-MB-231 cells with IC <subscript>50</subscript> equals 18.7 µM, which is better than that of piperine (IC <subscript>50</subscript> = 47.8 µM) and 5-FU (IC <subscript>50</subscript> = 38.5 µM). Furthermore, 8q was investigated for its possible mechanism of action in MDA-MB-231 cells via Annexin V-FITC apoptosis assay and cell cycle analysis. Moreover, an in-silico analysis has proposed VEGFR-2 as a probable enzymatic target for piperine-based derivatives, and then has explored the binding interactions within VEGFR-2 active site (PDB:4ASD). Finally, an in vitro VEGFR-2 inhibition assay was performed to validate the in silico findings, where 8q showed good VEGFR-2 inhibitory activity with IC <subscript>50</subscript> = 231 nM.
- Subjects :
- Alkaloids chemistry
Amides chemical synthesis
Amides chemistry
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Apoptosis drug effects
Benzodioxoles chemistry
Cell Cycle drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Piperidines chemistry
Polyunsaturated Alkamides chemistry
Protein Kinase Inhibitors chemical synthesis
Protein Kinase Inhibitors chemistry
Structure-Activity Relationship
Urea analogs & derivatives
Urea chemistry
Vascular Endothelial Growth Factor Receptor-2 metabolism
Alkaloids pharmacology
Amides pharmacology
Antineoplastic Agents pharmacology
Benzodioxoles pharmacology
Piperidines pharmacology
Polyunsaturated Alkamides pharmacology
Protein Kinase Inhibitors pharmacology
Urea pharmacology
Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1475-6374
- Volume :
- 37
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of enzyme inhibition and medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 34894962
- Full Text :
- https://doi.org/10.1080/14756366.2021.1988944