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*, Manojit Pal*.

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 10 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

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.

[1]
Jackson, J.M. TNF-alpha inhibitors. Dermatol. Ther., 2007, 20, 251-264.
[2]
Ma, X.; Xu, S. TNF inhibitor therapy for rheumatoid arthritis. Biomed. Rep., 2012, 1, 177-184.
[3]
Palladino, M.A.; Bahjat, F.R.; Theodorakis, E.A.; Moldawer, L.L. Anti-TNF-α therapies: The next generation. Nat. Rev. Drug Discov., 2003, 2, 736-746.
[4]
Donnelly, S.; Lloyd, D.; O’reilly, C.; Fayne, D. 3-Phenyl-7- Hydroxy-Isocoumarins as Macrophage Migration Inhibitory Factor (MIF) Inhibitors. US patent application number US 2017/0144983 A1, May 25, 2017.
[5]
Zidi, I.; Mestiri, S.; Bartegi, A.; Amor, N.B. TNF-alpha and its inhibitors in cancer. Med. Oncol., 2010, 27, 185-198.
[6]
Kawano, T.; Agata, N.; Kharbanda, S.; Avigan, D.; Kufe, D. A novel isocoumarin derivative induces mitotic phase arrest and apoptosis of human multiple myeloma cells. Cancer Chemother. Pharmacol., 2007, 59, 329-335.
[7]
Nakashima, T.; Hirano, S.; Agata, N.; Kumagai, H.; Isshiki, K.; Yoshioka, T.; Ishizuka, M.; Maeda, K.; Takeuchi, T. Inhibition of angiogenesis by a new isocoumarin, NM-3. J. Antibiot. (Tokyo), 1999, 52, 426-428.
[8]
Oikawa, T.; Sasaki, M.; Inose, M.; Shimamura, M.; Kuboki, H.; Hirano, S.; Kumagai, H.; Ishizuka, M.; Takeuchi, T. Effects of cytogenin, a novel microbial product, on embryonic and tumor cell-induced angiogenic responses in vivo. Anticancer Res., 1997, 17, 1881-1886.
[9]
Pal, S.; Chatare, V.; Pal, M. Isocoumarin and its derivatives: An overview on their synthesis and applications. Curr. Org. Chem., 2011, 15, 782-800.
[10]
Ashraf, Z. Metal-catalyzed synthesis of isocoumarin derivatives (microreview). Chem. Heterocycl. Compd., 2016, 52, 149-151.
[11]
Saeed, A.; Haroon, M.; Muhammad, F.; Larik, F.A.; Hesham, E-S.; Channar, P.A. Advances in transition metal catalyzed synthesis of 3-substituted isocoumarins. J. Organomet. Chem., 2017, 834, 88-103.
[12]
Pal, S.; Pal, M. Isocoumarin, thiaisocoumarin and phosphaisocoumarin: Natural occurrences, synthetic approaches and pharmaceutical applications. Elsevier 2018, Paperback ISBN: 9780128154113.
[13]
Kumar, Y.S.; Dasaradhan, C.; Prabakaran, K.; Manivel, P.; Khan, F-R.N.; Jeong, E.D.; Chung, E.H. Palladium catalyzed Suzuki Miyaura cross coupling of 3-chlroisochromen-1-one: Synthesis of glomellin and reticulol analogues. Tetrahedron Lett., 2015, 56, 941-945.
[14]
Marck, G.; Villiger, A.; Buchecker, R. Aryl couplings with heterogeneous palladium catalysts. Tetrahedron Lett., 1994, 35, 3277-3280.
[15]
Gala, D.; Stamford, A.; Jenkins, J.; Kugelman, M. One-Step Synthesis of Biphenylacetic Acids via Pd/C-Catalyzed Arylation. Org. Process Res. Dev., 1997, 1, 163-164.
[16]
Ennis, D.S.; McManus, J.; Wood-Kaczmar, W.; Richardoson, J.; Smith, G.E.; Carstairs, A. Multikilogram-scale synthesis of a biphenyl carboxylic acid derivative using a Pd/C-mediated Suzuki coupling approach. Org. Process Res. Dev., 1999, 3, 248-252.
[17]
LeBlond, C.R.; Andrews, A.T.; Sun, Y.; Sowa, Jr, J.R. Activation of aryl chlorides for Suzuki cross-coupling by ligandless, heterogenous palladium. Org. Lett., 2001, 3, 1555-1557.
[18]
Felpin, F-X.; Ayad, T.; Mitra, S. Pd/C: An Old Catalyst for New Applications – Its Use for the Suzuki–Miyaura Reaction. Eur. J. Org. Chem., 2006, 2006, 2679-2690.
[19]
Cella, R.; Stefani, H.A. Ultrasonic reactions, in green techniques for organic synthesis and medicinal chemistry (eds W. Zhang and B. W. Cue), John Wiley & Sons, Ltd, Chichester, UK. 2012. doi: 10.1002/9780470711828.ch13.
[20]
Polácková, V.; Hut’ka, M.; Toma, S. Ultrasound effect on Suzuki reactions. 1. Synthesis of unsymmetrical biaryls. Ultrason. Sonochem., 2005, 12, 99-102.
[21]
Amatore, C.; Jutand, A.; Le Duc, G. Kinetic data for the transmetalation/reductive elimination in palladium-catalyzed suzuki-miyaura reactions: Unexpected triple role of hydroxide ions used as base. Chem. - A Eur. J., 2011, 17, 2492-2503.
[22]
Chen, J-S.; Vasiliev, A.N.; Panarello, A.P.; Khinast, J.G. Pd-leaching and Pd-removal in Pd/C-catalyzed Suzuki couplings. Appl. Catal. A Gen., 2007, 325, 76-86.
[23]
Parsa, K.V.; Ganesan, L.P.; Rajaram, M.V.; Gavrilin, M.A.; Balagopal, A.; Mohapatra, N.P.; Wewers, M.D.; Schlesinger, L.S.; Gunn, J.S.; Tridandapani, S. Macrophage pro-inflammatory response to Francisella novicida infection is regulated by SHIP. PLoS Pathog., 2006, 2e71
[24]
Sun, H.; Yost, G.S. Metabolic activation of a novel 3-substituted indole-containing TNF-α inhibitor: Dehydrogenation and inactivation of CYP3A4. Chem. Res. Toxicol., 2008, 21, 374-385.
[25]
Beslija, S. The role of anthracyclines / anthraquinones in metastatic breast cancer. Breast Cancer Res. Treat., 2003, 81, 25-32.
[26]
Lown, J.W. Anthracycline and anthraquinone anticancer agents: Current status and recent developments. Pharmacol. Ther., 1993, 60, 185-214.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 10
Year: 2019
Page: [842 - 850]
Pages: 9
DOI: 10.2174/1389557519666190130163708
Price: $58

Article Metrics

PDF: 17
HTML: 3