Generic placeholder image

Current Organic Synthesis

Author(s): Min-Xin Li, Xiao-Jia Pu, Xia Zhang, Xi Zheng, Hui Gao, Wei-Lie Xiao, Chun-Ping Wan* and Ze-Wei Mao*

DOI: 10.2174/1570179417666200124103400

DownloadDownload PDF Flyer Cite As
Synthesis and Biological Evaluation of Heterocyclic Substituted Bis(indolyl)methanes

Page: [144 - 150] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Background: Bis(indolyl)methane derivatives are widely found in nature with a broad range of biological and pharmacological activities. The development of techniques for the synthesis and functionalization of bis(indolyl)methanes have attracted more and more attention in recent years.

Objective: To study the synthesis and biological activity of heterocyclic substituted bis(indolyl)methanes.

Materials and Methods: A series of heterocyclic substituted bis(indolyl)methanes (3a-3p) have been prepared by condensation reaction of indole and heterocyclic aldehydes catalyzed by boron trifluoride etherate with high yields. Preliminary in vitro anti-inflammatory in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and cytotoxic activity against human tumor cell lines (A549, Hela and SGC7901) by MTT assay were tested.

Results: The result indicated that heterocyclic substituted bis(indolyl)methanes showed good antiinflammatory and selective cytotoxic activity. Especially, compounds 3o, 3p and 3q displayed similar inhibitory effect on the generation of NO to positive control dexamethasone, and compound 3q displayed similar selective cytotoxic activity to 5-FU.

Conclusion: Heterocyclic substituted bis(indolyl)methanes may be used as potential anti-inflammatory and anticancer leads.

Keywords: Synthesis, bis(indolyl)methanes, anti-inflammatory activity, cytotoxic activity, heterocyclic, anticancer leads.

Graphical Abstract

[1]
Singh, T.P.; Singh, O.M. Recent progress in biological activities of indole and indole alkaloids. Mini Rev. Med. Chem., 2018, 18(1), 9-25.
[PMID: 28782480]
[2]
Konopelski, P.; Ufnal, M. Indoles-Gut bacteria metabolites of tryptophan with pharmacotherapeutic potential. Curr. Drug Metab., 2018, 19(10), 883-890. Available at
[http://dx.doi.org/10.2174/1389200219666180427164731] [PMID: 29708069]
[3]
Kaur, J.; Utreja, D. Ekta; Jain, N.; Sharma, S. Recent developments in the synthesis and antimicrobial activity of indole and its derivatives. Curr. Org. Synth., 2019, 16, 17-37. Available at
[http://dx.doi.org/10.2174/1570179415666181113144939]
[4]
Nemallapudi, B.R.; Zyryanov, G.V.; Avula, B.; Guda, M.R.; Cirandur, S.R.; Venkataramaiah, C.; Rajendra, W.; Gundala, S. Meglumine as a green, efficient and reusable catalyst for synthesis and molecular docking studies of bis(indolyl)methanes as antioxidant agents. Bioorg. Chem., 2019, 87, 465-473. Available at
[http://dx.doi.org/10.1016/j.bioorg.2019.03.005] [PMID: 30927587]
[5]
Maestro, A.; Martín-Encinas, E.; Alonso, C.; Martinez de Marigorta, E.; Rubiales, G.; Vicario, J.; Palacios, F. Synthesis of novel antiproliferative hybrid bis-(3-indolyl)methane phosphonate derivatives. Eur. J. Med. Chem., 2018, 158, 874-883. Available at
[http://dx.doi.org/10.1016/j.ejmech.2018.09.011] [PMID: 30253344]
[6]
Osawa, T.; Namiki, M. Structure elucidation of streptindole: A novel genotoxic metabolite isolated from intestinal bacteria. Tetrahedron Lett., 1983, 24, 4719-4722. Available at
[http://dx.doi.org/10.1016/S0040-4039(00)86237-1]
[7]
Zendah, I.; Shaaban, K.A.; Helmke, E.; Maier, A.; Fiebig, H.H.; Laatsch, H. Barakacin: A thiazolyl-indole alkaloid isolated from a ruminal Pseudomonas sp. Z. Naturforsch. B, 2012, 67, 417-420. Available at
[http://dx.doi.org/10.5560/znb.2011-0277]
[8]
Kasar, S.B.; Thopate, S.R. Synthesis of bis(indolyl)methanes using naturally occurring, biodegradable itaconic acid as a green and reusable catalyst. Curr. Org. Synth., 2018, 12, 110-115. Available at
[http://dx.doi.org/10.2174/1570179414666170621080701]
[9]
Shaikh, S.I.; Zaheer, Z.; Mokale, S.N. A simple and efficient supramolecular chemistry approach for synthesis of bis(indolyl)methanes using aqueous β-cyclodextrin as green promoter host. Lett. Org. Chem., 2018, 15, 32-38. Available at
[http://dx.doi.org/10.2174/1570178614666170811123132]
[10]
Safe, S.; Papineni, S.; Chintharlapalli, S. Cancer chemotherapy with indole-3-carbinol, bis(3′-indolyl)methane and synthetic analogs. Cancer Lett., 2008, 269(2), 326-338. Available at
[http://dx.doi.org/10.1016/j.canlet.2008.04.021] [PMID: 18501502]
[11]
Deb, M.L.; Deka, B.; Saikia, P.J.; Baruah, P.K. Base-promoted three-component cascade approach to unsymmetrical bis(indolyl)methanes. Tetrahedron Lett., 2017, 58, 1999-2003. Available at
[http://dx.doi.org/10.1016/j.tetlet.2017.04.032]
[12]
Sarva, S.; Harinath, J.S.; Sthanikam, S.P.; Ethiraj, S.; Vaithiyalingam, M.; Cirandur, S.R. Synthesis, antibacterial and anti-inflammatory activity of bis(indolyl)methanes. Chin. Chem. Lett., 2016, 27, 16-20. Available at
[http://dx.doi.org/10.1016/j.cclet.2015.08.012]
[13]
Joshi, R.S.; Mandhane, P.G.; Diwakar, S.D.; Gill, C.H. Ultrasound assisted green synthesis of bis(indol-3-yl)methanes catalyzed by 1-hexenesulphonic acid sodium salt. Ultrason. Sonochem., 2010, 17(2), 298-300. Available at
[http://dx.doi.org/10.1016/j.ultsonch.2009.08.015] [PMID: 19767231]
[14]
Gong, H.W.; Xie, Z.F. Research progress of synthesis of bis(indolyl)methanes. Youji Huaxue, 2012, 32, 1195-1207. Available at
[http://dx.doi.org/10.6023/cjoc1110263]
[15]
Mathavan, S.; Kannan, K.; Yamajala, R.B.R.D. Thiamine hydrochloride as a recyclable organocatalyst for the synthesis of bis(indolyl)methanes, tris(indolyl)methanes, 3,3-di(indol-3-yl)indolin-2-ones and biscoumarins. Org. Biomol. Chem., 2019, 17(44), 9620-9626. Available at
[http://dx.doi.org/10.1039/C9OB02090J] [PMID: 31664290]
[16]
Tuengpanya, S.; Chantana, C.; Sirion, U.; Siritanyong, W.; Srisook, K.; Jaratjaroonphong, J. One-pot solvent-free synthesis of triaryl- and triheteroarylmethanes by Bi(OTf)3-catalyzed Friedel-Crafts reaction of arenes/heteroarenes with trialkyl orthoformates. Tetrahedron, 2018, 74, 4373-4380. Available at
[http://dx.doi.org/10.1016/j.tet.2018.05.079]
[17]
Ma, Y.; Zheng, X.; Zhu, P.; Liu, B.; Gao, H.; Mao, Z.; Zhang, L.; Wan, C. Novel resveratrol-chalcone derivatives: Synthesis and biological evaluation. Mini Rev. Med. Chem., 2019, 19(5), 424-436. Available at
[http://dx.doi.org/10.2174/1389557518666180727165358] [PMID: 30058485]
[18]
Gao, H.; Liu, B.; Zhu, P.; Zhang, L.J.; Wan, C.P.; Rao, G.X.; Mao, Z.W. Synthesis and biological evaluation of new piperazine substituted 3, 5-diarylisoxazolines. Curr. Org. Synth., 2019, 16, 294-302. Available at
[http://dx.doi.org/10.2174/1570179416666181203121031]
[19]
Gao, H.; Zheng, X.; Zhu, P.; Wang, S.; Wan, C.; Rao, G.; Mao, Z. Synthesis and biological evaluation of novel substituted chalcone-piperazine derivatives. Youji Huaxue, 2018, 38, 684-691. Available at
[http://dx.doi.org/10.6023/cjoc201707034]
[20]
Gao, H.; Zhang, X.; Pu, X.J.; Zheng, X.; Liu, B.; Rao, G.X.; Wan, C.P.; Mao, Z.W. 2-Benzoylbenzofuran derivatives possessing piperazine linker as anticancer agents. Bioorg. Med. Chem. Lett., 2019, 29(6), 806-810. Available at
[http://dx.doi.org/10.1016/j.bmcl.2019.01.025] [PMID: 30709651]
[21]
Vural, P.; Degirmencioglu, S.; Erden, S.; Gelincik, A. The relationship between transforming growth factor-β1, vascular endothelial growth factor, nitric oxide and Hashimoto’s thyroiditis. Int. Immunopharmacol., 2009, 9(2), 212-215. Available at
[http://dx.doi.org/10.1016/j.intimp.2008.11.003] [PMID: 19028605]