Dihydronaphthalenone chalconoid derivatives as potential cathepsin B inhibitors; design, synthesis, cytotoxicity evaluation and docking analysis
Document title: Dihydronaphthalenone chalconoid derivatives as potential cathepsin B inhibitors; design, synthesis, cytotoxicity evaluation and docking analysis
Journal: Brazilian Journal of Pharmaceutical Sciences
Database: PERIÓDICA
System number: 000451568
ISSN: 1984-8250
Authors: 1
2
2
3
3
2
Institutions: 1Shiraz University of Medical Sciences, Pharmaceutical Sciences Research Center, Shiraz. Irán
2Shiraz University of Medical Sciences, School of Pharmacy, Shiraz. Irán
3Shiraz University of Medical Sciences, Medicinal and Natural Products Chemistry Research Center, Shiraz. Irán
Year:
Volumen: 57
Country: Brasil
Language: Inglés
Document type: Artículo
Approach: Experimental, aplicado
English abstract Cathepsin B, an abundant expressed cysteine peptidase, plays a key role in cancer cell proliferation, tumor metastasis, apoptosis, angiogenesis, invasion and migration. Therefore, development of cathepsin B inhibitors to treat cancer is of great significance. In this study, dihydronaphthalenone chalconoid derivatives containing different benzyliden moieties were synthesized via an efficient route in microwave condition that resulted in the desired compounds in high yields compared to acid- or base-catalyzed refluxing conditions. Cytotoxicity of the compounds was evaluated against K562, HT-29 and MCF-7 human cancer cell lines by MTT assay. P1, P3 and P9 (containing 4-OCH3, 3-NO2 and 4-CN moieties on phenyl ring, respectively) exhibited good cytotoxic activity with an IC50 range of 7.1-28.9 μM. Molecular docking analysis was carried out to investigate the possible interactions and binding modes of all compounds with cathepsin B. The most promising compounds, P1, P3 and P9 were well accommodated within the active site and had the least estimated free binding energies. It was concluded from both MTT assay and docking studies that some dihydronaphthalenone chalconoid derivatives could be suggested as effective cytotoxic agents and potential cathepsin B inhibitors
Disciplines: Química
Keyword: Química farmacéutica,
Proliferación celular,
Cáncer,
Catepsina B,
Inhibición,
Reacciones aldol,
Benciliden-dihidronaftalenona,
Chalconas,
Cisteína proteasa,
Síntesis asistida por microondas
Keyword: Medicinal chemistry,
Cell proliferation,
Cancer,
Cathepsin B,
Inhibition,
Aldol reactions,
Benzylidene-dihydronaphthalenone,
Chalcones,
Cysteine protease,
Microwave assisted synthesis
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