Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis of 2-substituted Furo[3,2-b]pyridines Under Pd/C-Cu Catalysis Assisted by Ultrasound: Their Evaluation as Potential Cytotoxic Agents

Author(s): Dandamudi Sri Laxmi, Suryadevara V. Vardhini, Venkata R. Guttikonda, Mandava V.B. Rao* and Manojit Pal*

Volume 20, Issue 8, 2020

Page: [932 - 940] Pages: 9

DOI: 10.2174/1871520620666200311102304

Price: $65

conference banner
Abstract

Background: Compounds containing furo[3,2-b]pyridine framework have shown interesting pharmacological properties, including anticancer activities. Though these compounds are generally synthesized via the heteroannulation processes involving acetylenic derivatives, some of them are complex.

Objective: The study aimed to explore a series of 2-substituted furo[3,2-b]pyridines for their cytotoxic properties against cancer cell lines in vitro.

Methods: We developed a convenient synthesis of 2-substituted furo[3,2-b]pyridines via sequential (i) C-C coupling followed by (ii) C-O bond-forming reactions in a single pot. The reactions were performed under ultrasound irradiation in the presence of Pd/C as an inexpensive, stable and widely used catalyst. A range of 2- substituted furo[3,2-b]pyridines were synthesized via coupling of 3-chloro-2-hydroxy pyridine with terminal alkynes in the presence of 10% Pd/C-CuI-PPh3-Et3N in EtOH. The in vitro evaluation of all these compounds was carried out against MDA-MB-231 and MCF-7 cell lines and subsequently against SIRT1.

Results: The furo[3,2-b]pyridine derivative 3b showed encouraging growth inhibition of both MDAMB-231 and MCF-7 cell lines and inhibition of SIRT1. The compound 3b also showed apoptosis-inducing potential when tested against MCF-7 cells.

Conclusion: The Pd/C-Cu catalysis under ultrasound accomplished a one-pot and direct access to 2-substituted furo[3,2-b]pyridine derivatives, some of which showed anticancer properties.

Keywords: Furo[3, 2-b]pyridine, ultrasound, Pd/C, cancer, catalysis, cytotoxic agents.

« Previous Next »
Graphical Abstract

[1]
Khanam, H.; Shamsuzzaman, Bioactive Benzofuran derivatives: A review. Eur. J. Med. Chem., 2015, 97, 483-504.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.039] [PMID: 25482554]
[2]
Němec, V.; Hylsová, M.; Maier, L.; Flegel, J.; Sievers, S.; Ziegler, S.; Schröder, M.; Berger, B-T.; Chaikuad, A.; Valčíková, B.; Uldrijan, S.; Drápela, S.; Souček, K.; Waldmann, H.; Knapp, S.; Paruch, K. Furo[3,2-b]pyridine: A privileged scaffold for highly selective kinase inhibitors and effective modulators of the hedgehog pathway. Angew. Chem. Int. Ed., 2018, 57, 1-6.
[PMID: 30569600]
[3]
Nakhi, A.; Rahman, M.S.; Seerapu, G.P.K.; Banote, R.K.; Kumar, K.L.; Kulkarni, P.; Haldar, D.; Pal, M. Transition metal free hydrolysis/cyclization strategy in a single pot: synthesis of fused furo N-heterocycles of pharmacological interest. Org. Biomol. Chem., 2013, 11(30), 4930-4934.
[http://dx.doi.org/10.1039/c3ob41069b] [PMID: 23824158]
[4]
Michan, S.; Sinclair, D. Sirtuins in mammals: insights into their biological function. Biochem. J., 2007, 404(1), 1-13.
[http://dx.doi.org/10.1042/BJ20070140] [PMID: 17447894]
[5]
Bedalov, A.; Gatbonton, T.; Irvine, W.P.; Gottschling, D.E.; Simon, J.A. Identification of a small molecule inhibitor of Sir2p. Proc. Natl. Acad. Sci. USA, 2001, 98(26), 15113-15118.
[http://dx.doi.org/10.1073/pnas.261574398] [PMID: 11752457]
[6]
Mlandenovic, S.A.; Castro, C.E. Cu(I) substitutions. furo[3,2‐b] pyridines, furo[3,2‐c] pyridines and 1h‐thieno[3,4‐b] 2‐pyran‐l‐ones from cuprous acetylides. J. Heterocycl. Chem., 1968, 5, 227-230.
[http://dx.doi.org/10.1002/jhet.5570050213]
[7]
Wang, J-R.; Manabe, K. Hydroxyterphenylphoshine-palladium catalyst for benzo[b]furan synthesis from 2-chlorophenols. bifunctional ligand strategy for cross-coupling of chloroarenes. J. Org. Chem., 2010, 75(15), 5340-5342.
[http://dx.doi.org/10.1021/jo1007948] [PMID: 20578763]
[8]
Zou, W.; Huang, Z.; Jiang, K.; Wu, Y.; Xue, Y.; Suzenet, F.; Sun, Q.; Guillaumet, G. Chelation-assisted C-S activation/cascade heteroannulation of pyridine-2-thione derivatives in Pd-catalyzed cross-coupling reaction with alkynes. Tetrahedron, 2017, 73, 5485-5492.
[http://dx.doi.org/10.1016/j.tet.2017.07.026]
[9]
Cella, R.; Stefani, H.A. Ultrasonic reactions.In Green Techniques for Organic Synthesis and Medicinal Chemistry; Zhang, W.; Cue, B.W., Eds.; John Wiley & Sons, Ltd: Chichester, UK, 2012.
[http://dx.doi.org/10.1002/9780470711828.ch13]
[10]
Pizzuti, L.; Franco, M.S.F.; Flores, A.F.C.; Quina, F.H.; Pereira, C.M.P. Recent Advances in the Ultrasound-Assisted Synthesis of Azoles.In Green Chemistry - Environmentally Benign Approaches; Kidwai, M., Ed.; InTech, 2012.
[http://dx.doi.org/10.5772/35171]
[11]
Puri, S.; Kaur, B.; Parmar, A.; Kumar, H. Applications of ultrasound in organic synthesis - a green approach. Curr. Org. Chem., 2013, 17, 1790-1828.
[http://dx.doi.org/10.2174/13852728113179990018]
[12]
Reddy, D.N.K.; Chandrasekhar, K.B.; Ganesh, Y.S.S.; Reddy, G.R.; Kumar, J.P.; Kapavarapu, R.K.; Pal, M. FeF3-catalyzed MCR in PEG-400: Ultrasound assisted synthesis of N-substituted 2-aminopyridines. RSC Advances, 2016, 6, 67212-67217.
[http://dx.doi.org/10.1039/C6RA14228A]
[13]
Milne, J.C.; Lambert, P.D.; Schenk, S.; Carney, D.P.; Smith, J.J.; Gagne, D.J.; Jin, L.; Boss, O.; Perni, R.B.; Vu, C.B.; Bemis, J.E.; Xie, R.; Disch, J.S.; Ng, P.Y.; Nunes, J.J.; Lynch, A.V.; Yang, H.; Galonek, H.; Israelian, K.; Choy, W.; Iffland, A.; Lavu, S.; Medvedik, O.; Sinclair, D.A.; Olefsky, J.M.; Jirousek, M.R.; Elliott, P.J.; Westphal, C.H. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature, 2007, 450(7170), 712-716.
[http://dx.doi.org/10.1038/nature06261] [PMID: 18046409]
[14]
Nasreen, A.; Adapa, S.R. An efficient facile and selective hydroxylation of nitrogen heterocycles. Heterocycl. Commun., 2001, 7, 501-506.
[http://dx.doi.org/10.1515/HC.2001.7.5.501]
[15]
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.
[http://dx.doi.org/10.1016/j.apcata.2007.03.010]
[16]
Köhler, K.; Heidenreich, R.G.; Krauter, J.G.; Pietsch, J. Highly active palladium/activated carbon catalysts for Heck reactions: correlation of activity, catalyst properties, and Pd leaching. Chemistry, 2002, 8(3), 622-631.
[http://dx.doi.org/10.1002/1521-3765(20020201)8:3<622:AID-CHEM622>3.0.CO;2-0] [PMID: 11859857]
[17]
Sonogashira, K.; Tohda, Y.; Hagihara, N. A convenient synthesis of acetylenes: Catalytic substitutions of acetylenic hydrogen with bromoalkenes, iodoarenes and bromopyridines. Tetrahedron Lett., 1975, 16, 4467-4470.
[http://dx.doi.org/10.1016/S0040-4039(00)91094-3]
[18]
Plumb, J.A. Cell sensitivity assays: the MTT assay. Methods Mol. Med., 2004, 88, 165-169.
[PMID: 14634227]
[19]
Li, H.; Li, H.; Qu, H.; Zhao, M.; Yuan, B.; Cao, M.; Cui, J. Suramin inhibits cell proliferation in ovarian and cervical cancer by downregulating heparanase expression. Cancer Cell Int., 2015, 15, 52.
[http://dx.doi.org/10.1186/s12935-015-0196-y] [PMID: 26052253]
[20]
Chipuk, J.E.; Kuwana, T.; Bouchier-Hayes, L.; Droin, N.M.; Newmeyer, D.D.; Schuler, M.; Green, D.R. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science, 2004, 303(5660), 1010-1014.
[http://dx.doi.org/10.1126/science.1092734] [PMID: 14963330]
[21]
Majumdar, P.; Bathula, C.; Basu, S.M.; Das, S.K.; Agarwal, R.; Hati, S.; Singh, A.; Sen, S.; Das, B.B. Design, synthesis and evaluation of thiohydantoin derivatives as potent topoisomerase I (Top1) inhibitors with anticancer activity. Eur. J. Med. Chem., 2015, 102, 540-551.
[http://dx.doi.org/10.1016/j.ejmech.2015.08.032] [PMID: 26312433]
[22]
Hati, S.; Tripathy, S.; Dutta, P.K.; Agarwal, R.; Srinivasan, R.; Singh, A.; Singh, S.; Sen, S. Spiro[pyrrolidine-3, 3´-oxindole] as potent anti-breast cancer compounds: Their design, synthesis, biological evaluation and cellular target identification. Sci. Rep., 2016, 6, 32213.
[http://dx.doi.org/10.1038/srep32213] [PMID: 27573798]
[23]
Kumar, N.; Hati, S.; Munshi, P.; Sen, S.; Sehrawat, S.; Singh, S. A novel spiroindoline targets cell cycle and migration via modulation of microtubule cytoskeleton. Mol. Cell. Biochem., 2017, 429(1-2), 11-21.
[http://dx.doi.org/10.1007/s11010-016-2932-6] [PMID: 28213771]
[24]
Tangutur, A.D.; Kumar, D.; Krishna, K.V.; Kantevari, S. Microtubule targeting agents as cancer chemotherapeutics: An overview of molecular hybrids as stabilizing and destabilizing agents. Curr. Top. Med. Chem., 2017, 17(22), 2523-2537.
[http://dx.doi.org/10.2174/1568026617666170104145640] [PMID: 28056738]
[25]
Loong, H.H.; Yeo, W. Microtubule-targeting agents in oncology and therapeutic potential in hepatocellular carcinoma. OncoTargets Ther., 2014, 7, 575-585.
[PMID: 24790457]
[26]
Hati, S.; Kumar Dutta, P.; Dutta, S.; Munshi, P.; Sen, S. Accessing benzimidazoles via a ring distortion strategy: An oxone mediated tandem reaction of 2-aminobenzylamines. Org. Lett., 2016, 18(13), 3090-3093.
[http://dx.doi.org/10.1021/acs.orglett.6b01217] [PMID: 27331245]

Rights & Permissions Print Cite
Article Metrics
27
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy