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: 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: 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: 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.