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Mini-Reviews in Medicinal Chemistry


ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Research Article

Ultrasound Assisted Synthesis of 3-(het)aryl Isocoumarin Derivatives and their in vitro Pharmacological Evaluation

Author(s): Gutta Lakshmi Prasanna, V.D. Nagendra Kumar Abbaraju, Yarlagadda Bharath, Mandava V. Basaveswara Rao* and Manojit Pal*

Volume 19, Issue 10, 2019

Page: [842 - 850] Pages: 9

DOI: 10.2174/1389557519666190130163708

Price: $65


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.

Keywords: Isocoumarin, Suzuki-Miyaura coupling, Pd/C, TNF-α, inhibition, pharmacological evaluation.

Graphical Abstract
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