Ultrasound Assisted Synthesis of 3-(het)aryl Isocoumarin Derivatives and their in vitro Pharmacological Evaluation.
Animals
Antineoplastic Agents
/ chemical synthesis
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Hep G2 Cells
Humans
Isocoumarins
/ chemical synthesis
MCF-7 Cells
Mice
Molecular Docking Simulation
Molecular Structure
RAW 264.7 Cells
Structure-Activity Relationship
Tumor Necrosis Factor-alpha
/ antagonists & inhibitors
Ultrasonic Waves
Isocoumarin
Pd/C
Suzuki-Miyaura coupling
TNF-α
inhibition
pharmacological evaluation.
Journal
Mini reviews in medicinal chemistry
ISSN: 1875-5607
Titre abrégé: Mini Rev Med Chem
Pays: Netherlands
ID NLM: 101094212
Informations de publication
Date de publication:
2019
2019
Historique:
received:
12
06
2018
revised:
22
09
2018
accepted:
22
01
2019
pubmed:
2
2
2019
medline:
7
8
2019
entrez:
2
2
2019
Statut:
ppublish
Résumé
In view of numerous biological activities of 3-substituted isocoumarins a number of analogues based on this scaffold were synthesized for their in vitro pharmacological evaluation. The syntheses of 3-substituted isocoumarins were carried out via a Pd/C-catalyzed Suzuki- Miyaura coupling of 3-chloroisochromen-1-one with a range of boronic acid derivatives. This C-C bond forming reaction was facilitated by ultrasound irradiation to afford the desired products in good yields. A number of 3-(het)aryl isocoumarin derivatives were prepared by using this methodology and subsequently tested for their TNF-α inhibitory properties in vitro followed by cytotoxicities via the MTT assay. Several compounds showed inhibition of TNF-α with one compound showing an IC50 value of 9.01±1.25 µM. Three compounds also showed promising cytotoxic properties against two cancer cell lines with IC50 ~ 0.9-2.7 µM. The isocoumarin framework could be an effective template for the design and discovery of new inhibitor of TNF-α for the potential treatment of related diseases.
Sections du résumé
BACKGROUND
BACKGROUND
In view of numerous biological activities of 3-substituted isocoumarins a number of analogues based on this scaffold were synthesized for their in vitro pharmacological evaluation.
METHODS
METHODS
The syntheses of 3-substituted isocoumarins were carried out via a Pd/C-catalyzed Suzuki- Miyaura coupling of 3-chloroisochromen-1-one with a range of boronic acid derivatives. This C-C bond forming reaction was facilitated by ultrasound irradiation to afford the desired products in good yields. A number of 3-(het)aryl isocoumarin derivatives were prepared by using this methodology and subsequently tested for their TNF-α inhibitory properties in vitro followed by cytotoxicities via the MTT assay.
RESULTS
RESULTS
Several compounds showed inhibition of TNF-α with one compound showing an IC50 value of 9.01±1.25 µM. Three compounds also showed promising cytotoxic properties against two cancer cell lines with IC50 ~ 0.9-2.7 µM.
CONCLUSION
CONCLUSIONS
The isocoumarin framework could be an effective template for the design and discovery of new inhibitor of TNF-α for the potential treatment of related diseases.
Identifiants
pubmed: 30706808
pii: MRMC-EPUB-96233
doi: 10.2174/1389557519666190130163708
doi:
Substances chimiques
Antineoplastic Agents
0
Isocoumarins
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Langues
eng
Pagination
842-850Informations de copyright
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