Gutta Lakshmi Prasanna, V. D. Nagendra Kumar Abbaraju, Yarlagadda Bharath, Mandava V. Basaveswara Rao and Manojit Pal* Pages 842 - 850 ( 9 )
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.
Isocoumarin, Suzuki-Miyaura coupling, Pd/C, TNF-α, inhibition, pharmacological evaluation.
Department of Chemistry, Krishna University, Machilipatnam-521001, Andhra Pradesh, Department of Chemistry, GIT, GITAM University, Visakhapatnam, Andhra Pradesh, Department of Chemistry, Krishna University, Machilipatnam-521001, Andhra Pradesh, Department of Chemistry, Krishna University, Machilipatnam-521001, Andhra Pradesh, Dr. Reddy’s Institute of Life Sciences, University of Hyderabad Campus, Hyderabad 500046