Lemon Juice Mediated Reaction under Ultrasound Irradiation: Synthesis of Indolofuroquinoxalines as Potential Anticancer Agents

Author(s): Gutta Lakshmi Prasanna, Bodapati Veera Durga Rao, Alugubelli Gopi Reddy, Mandava V. Basaveswara Rao*, Manojit Pal*

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 8 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: A non-hazardous synthetic methodology has been developed for the preparation of compounds based on indolofuroquinoxaline framework. Lemon juice that is known to play the role of a biocatalyst in various organic reactions was used for this purpose.

Method: A number of indolofuroquinoxaline derivatives were prepared via the lemon juice mediated condensation of methyl 2-(2-chloro-1H-indol-3-yl)-2-oxoacetate or its N-alkyl derivatives with 1,2- diamines under ultrasound irradiation. All the synthesized compounds were screened via an MTT assay for their potential anticancer properties in vitro using a number of cancer cell lines including MDA-MB 231, and MCF7, K562, Colo-205 and IMR-32 and the non-cancerous HEK293 cell line. Compounds 3a, 3b and 3c showed promising growth inhibition against K562, MDA-MB 231 and MCF7 cell lines but no significant effects on HEK293 cell line suggesting their selectivity towards cancer cells.

Results and Conclusion: Moreover, according to their IC50 values, all these compounds appeared to be relatively more potent towards K562 cell line over MDA-MB 231 and MCF7 cell lines indicating their potential against leukemia.

Keywords: Lemon juice, ultrasound, indolofuroquinoxaline, anticancer, MCF7, antitumor.

Harmenberg, J.; Akesson-Johansson, A.; Graslund, A.; Malmfors, T.; Bergman, J.; Wahren, B.; Akerfeldt, S.; Lundbal, L.; Cox, S. The mechanism of action of the anti-herpes virus compound 2,3-dimethyl-6(2-dimethylaminoethyl)-6H-indolo-(2,3-b)quinoxaline. Antiviral Res., 1991, 15, 193-204.
Hirata, K.; Araya, J.; Nakaike, S.; Kitamura, K.; Ishida, T. Side chain-dependent binding of antitumor indoloquinoxaline derivatives to DNA: Comparative spectroscopic and viscometric measurements. Chem. Pharm. Bull., 2001, 49, 44-48.
Hazeldine, S.T.; Polin, L.; Kushner, J.; White, K.; Corbett, T.H.; Horwitz, J.P. Synthesis and biological evaluation of conformationally constrained analogs of the antitumor agents XK469 and SH80. Part 5. Bioorg. Med. Chem., 2006, 14, 2462-2467.
For a review, see: Moorthy, N.S.; Manivannan, E.; Karthikeyan, C.; Trivedi, P. 6H-Indolo[2,3-b]quinoxalines: DNA and protein interacting scaffold for pharmacological activities. Mini Rev. Med. Chem., 2013, 13, 1415-1420.
Kumar, E.V.K.S.; Etukala, J.R. Ablordeppey. S.Y. Indolo[3,2-b]quinolines: Synthesis, Biological Evaluation and Structure Activity-Relationships. Mini Rev. Med. Chem., 2008, 8, 538-554.
Lavrado, J.; Ohnmacht, S.A.; Correia, I.; Leitao, C.; Pisco, S.; Gunaratnam, M.; Moreira, R.; Neidle, S.; dos Santos, D.J.V.A.; Paulo, A. Indolo[3,2-c]quinoline G-Quadruplex Stabilizers: A Structural analysis of binding to the human telomeric G-Quadruplex. ChemMedChem, 2015, 10, 836-849.
Kumar, S.; Bawa, S.; Gupta, H. Biological activities of quinoline derivatives. Mini Rev. Med. Chem., 2009, 9, 1648-1654.
Nikumbh, S.P.; Raghunadh, A.; Murthy, V.N.; Jinkala, R.; Joseph, S.C.; Murthy, Y.L.N.; Prasad, B.; Pal, M. A greener approach towards double heteroarylation of N, O and S nucleophiles: Synthesis of bioactive polynuclear fused N-Heteroarenes. RSC Advances, 2015, 5, 74570-74574.
Miller, R.B.; Dugar, S. A regiospecific total synthesis of ellipticine via nitrene insertion. Tetrahedron Lett., 1989, 30, 297-300.
Li, C.J.; Chan, T.H. Organic reactions in aqueous media; John Wiley & Sons: New York, 1997.
Pal, R. Fruit Juice: A natural, green and biocatalyst system in organic synthesis. Open J. Org. Chem, 2013, 1(4), 47-56.
Deshmukh, M.B.; Patil, S.S.; Jadhav, S.D.; Pawar, P.B. Green approach for Knoevenagel condensation of aromatic aldehydes. Synth. Commun., 2012, 42, 1177-1183.
Patil, S.; Jadhav, S.D.; Deshmuk, M.B. Natural acid catalyzed multi-component reactions as a green approach. Arch. Apll. Sci. Res, 2011, 3, 203-208.
Patil, S.; Jhadav, S.D.; Patil, U.P. Natural acid catalyzed synthesis of schiff base under solvent-free condition: As a green approach. Arch. Apll. Sci. Res, 2012, 4, 1074-1078.
Sachdeva, H.; Saroj, R.; Khaturia, S.; Dwivedi, D. Environ- Economic synthesis and characterization of some new 1,2,4- Triazole derivatives as organic fluorescent materials and potent fungicidal agents. In: Org. Chem. Int; , 2013. ID 659107, 19 pages.
Kumar; S.K.; Rambabu, D.; Kumar, C.H.V.; Sreenivas, B.Y.; Prasad, K.R.S.; Rao, M.V.B.; Pal, M. Catalysis by Amberlyst-15 under ultrasound in water: A green synthesis of 1,2,4-benzothiadiazine-1,1-dioxides and their spiro derivatives. RSC Advances, 2013, 3, 24863-24867.
Fröhner, W.; Monse, B.; Braxmeier, T.M.; Casiraghi, L.; Sahagún, H.; Seneci, P. Regiospecific Synthesis of Mono-N-substituted Indolopyrrolocarbazoles. Org. Lett., 2005, 7, 4573-4576.
Nelson, C.E. Lemon juice composition, US patent application number US2215334A, Dec 3, 1938.
Sharma, P.; Rashmi, S.; Kumar, G.V. Rapid synthesis of amides from ketoximes using citric acid monohydrate over TBAB under green chemistry conditions. J. Adv. Chem. Sci, 2016, 2, 180-182.
De la Fuente, J.R.; Cañete, A.; Zanocco, A.L.; Saitz, C.; Jullian, C. Formal hydride transfer mechanism for photoreduction of 3-Phenylquinoxalin-2-ones by amines. Association of 3-Phenylquinoxalin-2-one with aliphatic amines. J. Org. Chem., 2000, 65, 7949-7958.
Xie, L-Y.; Li, Y-J.; Qu, J.; Duan, Y.; Hu, J.; Liu, K-J.; Cao, Z.; He, W-M. A base-free, ultrasound accelerated one-pot synthesis of 2-sulfonylquinolines in water. Green Chem., 2017, 19, 5642-5646.
Wu, C.; Lu, L-H.; Peng, A-Z.; Jia, G-K.; Peng, C.; Cao, Z.; Tang, Z.; He, W-M.; Xu, X. Ultrasound-promoted Brønsted acid ionic liquid-catalyzed hydrothiocyanation of activated alkynes under minimal solvent conditions. Green Chem., 2018, 20, 3683-3688.
Mason, T.J.; Peters, D. Practical Sonochemistry; Ellis Horwood: New York, NY, USA, 1991.
Mason, T.J. Sonochemistry and the environment - providing a “green” link between chemistry, physics and engineering. Ultrason. Sonochem., 2007, 14, 476-483.
Jiang, J.; Zou, H.; Dong, Q.; Wang, R.; Lu, L.; Zhu, Y.; He, W. Synthesis of 2-Keto(hetero)aryl Benzox(thio)azoles through base promoted cyclization of 2-Amino(thio)phenols with α,α-Dihaloketones. J. Org. Chem., 2016, 81, 51-56.
Zhao, Y-H.; Luo, Y.; Zhu, Y.; Wang, H.; Zhou, H.; Tan, H.; Zhou, Z.; Ma, Y-C.; Xie, W.; Tang, Z. Synthesis of potential anticancer 1-(1H-Indol-3-yl)isoquinolines by silver nitrate mediated tandem reactions of 2-Alkynylbenzaldehyde azines and indoles. Synlett, 2018, 29, 773-778.
Zhao, Y-H.; Li, Y.; Luo, M.; Tang, Z.; Deng, K. Silver nitrate mediated cyclization/N–N Bond-Cleavage reaction for the synthesis of 3-Arylisoquinolines. Synlett, 2016, 27, 2597-2600.
Zhao, Y-H.; Li, Y.; Guo, T.; Tang, Z.; Xie, W.; Zhao, G. Selective synthesis of pyrazolo[5,1-a]isoquinolines via 1,3-dipolar cycloaddition reaction. Tetrahedron Lett., 2016, 57, 2257-2261.
Guo, T.; Liu, Y.; Zhao, Y-H.; Zhang, P-K.; Han, S-L.; Liu, H-M. Palladium-catalyzed external-oxidant-free coupling reactions between isoquinoline/quinoline N-oxides with olefins. Tetrahedron Lett., 2016, 57, 3920-3923.
Guo, T.; Liang, J.J.; Yang, S.; Chen, H.; Fu, Y.N.; Han, S.L.; Zhao, Y-H. Palladium-catalyzed oxidative C-H/C-H cross-coupling of imidazopyridines with azoles. Org. Biomol. Chem., 2018, 16, 6039-6046.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [671 - 678]
Pages: 8
DOI: 10.2174/1389557518666181029100044
Price: $65

Article Metrics

PDF: 17