Synthesis, Reaction and Biological Importance of Isatin Derivatives
DOI:
https://doi.org/10.48112/bcs.v1i3.221Abstract
Abstract Views: 597
Isatin is a heterocyclic nitrogen compound that has attracted much interest in recent years due to its diverse biological and pharmacological activities. It can be used in many medical and biological applications, such as antidiabetic, antibiotic, and anticancer agents. The isatin molecule can also be prepared from different substrates by various methods, such as the methods of Sandmeyer, Stolle, Gassman, Meanwell and Hewawasam and others. On the other hand, the isatin molecule can undergo various chemical reactions, such as oxidation, Friedel-Crafts reaction, ring expansion, aldol condensation, and alkylation reactions. As a result of these reactions, several biologically useful biomolecules are formed, including 2-oxindoles, tryptanthrin, indirubins and others. Therefore, the aim of this review was to provide an overview of the synthetic methods of the isatin molecule and its derivatives and to examine the various chemical reactions it undergoes. In addition, a list of some of the recently documented biological activities of isatin derivatives was compiled, such as antidiabetic, antibacterial, anticancer, and other properties.
Keywords:
Biological Activity, Isatin, Reactions, Synthesis
Metrics
References
Alvin Tan, C. X., Mei, G. J., & Lu, Y. (2021). Phosphine-catalyzed asymmetric allylic alkylation of achiral MBH carbonates with 3, 3′-bisindolines: enantioselective construction of quaternary stereogenic centers. Organic Letters, 23(5), 1787-1792. https://doi.org/10.1021/acs.orglett.1c00201
Bandini, M., Melloni, A., & Umani-Ronchi, A. (2004). New Catalytic Approaches in the Stereoselective Friedel–Crafts Alkylation Reaction. Angewandte Chemie International Edition, 43(5), 550-556. https://doi.org/10.1002/anie.200301679
da Costa, D. P., de Castro, A. C., da Silva, G. A., Lima-Junior, C. G., de Andrade Júnior, F. P., de Oliveira Lima, E., . . . da Silva, L. C. (2021). Microwave-assisted synthesis and antimicrobial activity of novel spiro 1,3,4-thiadiazolines from isatin derivatives. Journal of Heterocyclic Chemistry, 58(3), 766-776. https://doi.org/10.1002/jhet.4213
El-Ghamry, H. A., Fawzy, A., Farghaly, T. A., Bawazeer, T. M., Alqarni, N., Alkhatib, F. M., & Gaber, M. (2022). Evaluation of the efficiency of divalent cobalt and copper chelates based on isatin derivatives and thiosemicarbazide ligands as inhibitors for the corrosion of Sabic iron in acidic medium. Arabian Journal of Chemistry, 15(1), 103522. https://doi.org/10.1016/j.arabjc.2021.103522
Emami, S., Valipour, M., Kazemi Komishani, F., Sadati-Ashrafi, F., Rasoulian, M., Ghasemian, M., . .. Ahangar, N. (2021). Synthesis, in silico, in vitro and in vivo evaluations of isatin aroylhydrazones as highly potent anticonvulsant agents. Bioorganic Chemistry, 104943. https://doi.org/10.1016/j.bioorg.2021.104943
Erdmann, O. L. (1840). Untersuchungen über den Indigo. Journal für Praktische Chemie, 19(1), 321-362.
Fayed, E. A., Eldin, R. R. E., Mehany, A. B. M., Bayoumi, A. H., & Ammar, Y. A. (2021). Isatin-Schiff's base and chalcone hybrids as chemically apoptotic inducers and EGFR inhibitors; design, synthesis, anti-proliferative activities and in silico evaluation. Journal of Molecular Structure, 1234, 130159. https://doi.org/10.1016/j.molstruc.2021.130159
Franz, A. K., Gutierrez, E. G., Wong, C. J., & Sahin, A. H. (2011). Enantioselective and Regioselective Indium(III)-Catalyzed Addition of Pyrroles to Isatins. Organic Letters, 13(21), 5754-5757. https://doi.org/10.1021/ol202329s
Gassman, P. G., & Van Bergen, T. J. (1974). Oxindoles. New, general method of synthesis. Journal of the American Chemical Society, 96(17), 5508-5512. https://doi.org/10.1021/ja00824a029
Gassman, P. G., Cue, B. W., & Luh, T.-Y. (1977). A general method for the synthesis of isatins. The Journal of Organic Chemistry, 42(8), 1344-1348. https://doi.org/10.1021/jo00428a016
Ha, T. J., Lee, M. H., Oh, E., Kim, J. I., Song, S. B., & Kwak, D. (2020). α-Glucosidase Inhibitory Activity of the Ethanol Extract of Peanut (Arachis hypogaea L.) Skin. Korean Journal of Medicinal Crop Science, 28(1), 21-28. https://doi.org/10.7783/KJMCS.2020.28.1.21
Hou, H., Li, H., Han, Y., & Yan, C. (2018). Synthesis of visible-light mediated tryptanthrin derivatives from isatin and isatoic anhydride under transition metal-free conditions. Organic Chemistry Frontiers, 5(1), 51-54. https://doi.org/10.1039/C7QO00740J
Jamali, M. F., Gupta, E., Kumar, A., Kant, R., & Mohanan, K. (2020). Ag-Catalyzed Trifluoromethylative Ring Expansion of Isatins and Isatin Ketimines with Trifluorodiazoethane. Chemistry – An Asian Journal, 15(6), 757-761. https://doi.org/10.1002/asia.201901799
Jiang, S.-F., Xu, C., Zhou, Z.-W., Zhang, Q., Wen, X.-H., Jia, F.-C., & Wu, A.-X. (2018). Switchable Access to 3-Carboxylate-4-quinolones and 1-Vinyl-3-carboxylate-4-quinolones via Oxidative Cyclization of Isatins and Alkynes. Organic Letters, 20(14), 4231-4234. https://doi.org/10.1021/acs.orglett.8b01645
Jordan, M. A., & Wilson, L. (2004). Microtubules as a target for anticancer drugs. Nature Reviews Cancer, 4(4), 253-265. https://doi.org/10.1038/nrc1317
Jose, M. L. L. (2000). The New Drugs and the Strategies to Manage Epilepsy. Current Pharmaceutical Design, 6(8), 873-878. http://dx.doi.org/10.2174/1381612003400308
Kaur, K., Utreja, D., Dhillon, N. K., Pathak, R. K., & Singh, K. (2021). N-alkyl isatin derivatives: Synthesis, nematicidal evaluation and protein target identifications for their mode of action. Pesticide Biochemistry and Physiology, 171, 104736. https://doi.org/10.1016/j.pestbp.2020.104736
Laurent, A. (1840). Recherchessurlindigo. Annal Chimieet Physique, 3, 393-434.
Li, W., Zhao, S.-J., Gao, F., Lv, Z.-S., Tu, J.-Y., & Xu, Z. (2018). Synthesis and In Vitro Anti-Tumor, Anti-Mycobacterial and Anti-HIV Activities of Diethylene-Glycol-Tethered Bis-Isatin Derivatives. ChemistrySelect, 3(36), 10250-10254. https://doi.org/10.1002/slct.201802185
Liu, H., Yan, Y., Li, M., & Zhang, X. (2021). An enantioselective aza-Friedel–Crafts reaction of 5-aminoisoxazoles with isatin-derived N-Boc ketimines. Organic & Biomolecular Chemistry, 19(17), 3820-3824. https://doi.org/10.1039/D1OB00374G
Mahmoud, A. M., Geslevich, J., Kint, J., Depuydt, C., Huysse, L., Zalata, A., & Comhaire, F. H. (1998). Seminal plasma alpha-glucosidase activity and male infertility. Human Reproduction, 13(3), 591-595. https://doi.org/10.1093/humrep/13.3.591
Meenakshi, K., Gopal, N., & Sarangapani, M. (2014). Synthesis, characterization and antimicrobial activity of some novel Schiff and Mannich bases of isatin. Int J Pharm Pharm Sci, 6(6), 318-322.
Mehta, A., Zitzmann, N., Rudd, P. M., Block, T. M., & Dwek, R. A. (1998). α-Glucosidase inhibitors as potential broad based anti-viral agents. FEBS Letters, 430(1), 17-22. https://doi.org/10.1016/S0014-5793(98)00525-0
Mironov, M. A., & Mokrushin, V. S. (1998). Reaction of aromatic isocyanides with triethylamine: a new method for the synthesis of indole betaines. Mendeleev Communications, 8(6), 242-243. https://doi.org/10.1070/MC1998v008n06ABEH001017
Moskovkina, T. V., Denisenko, M. V., Kalinovskii, A. I., & Stonik, V. A. (2013). Synthesis of substituted tryptanthrins via oxidation of isatin and its derivatives. Russian Journal of Organic Chemistry, 49(12), 1740-1743. https://doi.org/10.1134/S1070428013120051
Obafemi, C. A., Adegbite, O. B., Fadare, O. A., Iwalewa, E. O., Omisore, N. O., Sanusi, K., . . . Ceylan, Ü. (2021). Tryptanthrin from microwave-assisted reduction of isatin using solid-state-supported sodium borohydride: DFT calculations, molecular docking and evaluation of its analgesic and anti-inflammatory activity. Heliyon, 7(1), e05756. https://doi.org/10.1016/j.heliyon.2020.e05756
Perucca, E. (2001). The Management of Refractory Idiopathic Epilepsies. Epilepsia, 42(s3), 31-35. https://doi.org/10.1046/j.1528-1157.2001.042suppl.3031.x
Qian, P., Su, J.-H., Wang, Y., Bi, M., Zha, Z., & Wang, Z. (2017). Electrocatalytic C–H/N–H Coupling of 2′-Aminoacetophenones for the Synthesis of Isatins. The Journal of Organic Chemistry, 82(12), 6434-6440. https://doi.org/10.1021/acs.joc.7b00635
Rahim, F., Taha, M., Iqbal, N., Hayat, S., Qureshi, F., Uddin, I., . . . Khan, K. M. (2020). Isatin based thiosemicarbazide derivatives as potential inhibitor of α-glucosidase, synthesis and their molecular docking study. Journal of Molecular Structure, 1222, 128922. https://doi.org/10.1016/j.molstruc.2020.128922
Reddy, R. M., Nageswara Rao, N., Ramakrishna, K., & Meshram, H. M. (2014). I2–DMSO promoted intramolecular oxidative cyclization of 2-(aryl or alkyl amino)-acetophenones for the synthesis of isatins. Tetrahedron Letters, 55(34), 4758-4762. https://doi.org/10.1016/j.tetlet.2014.06.062
Sagnou, M., Mavroidi, B., Kaminari, A., Boukos, N., & Pelecanou, M. (2020). Novel Isatin Thiosemicarbazone Derivatives as Potent Inhibitors of β-Amyloid Peptide Aggregation and Toxicity. ACS Chemical Neuroscience, 11(15), 2266-2276. https://doi.org/10.1021/acschemneuro.0c00208
Sandmeyer, T. (1919). Über isonitrosoacetanilide und deren Kondensation zu Isatinen. Helvetica Chimica Acta, 2(1), 234-242. https://doi.org/10.1002/hlca.19190020125
Satish, G., Polu, A., Ramar, T., & Ilangovan, A. (2015). Iodine-Mediated C–H Functionalization of sp, sp2, and sp3 Carbon: A Unified Multisubstrate Domino Approach for Isatin Synthesis. The Journal of Organic Chemistry, 80(10), 5167-5175. https://doi.org/10.1021/acs.joc.5b00581
Shams, F., Aliabad, J. M., & Rouhani, M. (2020). Asymmetric cross-aldol reaction of isatin and ketones catalyzed by crude earthworm extract as efficient biocatalyst. Green Chemistry Letters and Reviews, 13(3), 258-264. https://doi.org/10.1080/17518253.2020.1808084
Sharma, S., Gupta, M. K., Saxena, A. K., & Bedi, P. M. S. (2015). Triazole linked mono carbonyl curcumin-isatin bifunctional hybrids as novel anti tubulin agents: Design, synthesis, biological evaluation and molecular modeling studies. Bioorganic & Medicinal Chemistry, 23(22), 7165-7180. https://doi.org/10.1016/j.bmc.2015.10.013
Shimada, Y., Nishimura, E., Hoshina, H., Kobayashi, H., Higuchi, T., Eto, Y., . . . Ohashi, T. (2015). Proteasome Inhibitor Bortezomib Enhances the Activity of Multiple Mutant Forms of Lysosomal α-Glucosidase in Pompe Disease. In J. Zschocke, M. Baumgartner, E. Morava, M. Patterson, S. Rahman, & V. Peters (Eds.), JIMD Reports, Volume 18 (pp. 33-39). Berlin, Heidelberg: Springer Berlin Heidelberg.
Silva, J. F. M. d., Garden, S. J., & Pinto, A. C. (2001). The chemistry of isatins: a review from 1975 to 1999. Journal of the Brazilian Chemical Society, 12, 273-324. https://doi.org/10.1590/S0103-50532001000300002
Stollé, R., Bergdoll, R., Luther, M., Auerhahn, A., & Wacker, W. (1922). Über N‐substituierte Oxindole und Isatine. Journal für Praktische Chemie, 105(1), 137-148. https://doi.org/10.1002/prac.19301280101
Sumpter, W. C. (1944). The Chemistry of Isatin. Chemical Reviews, 34(3), 393-434. https://doi.org/10.1021/cr60109a003
Tangella, Y., Manasa, K. L., Krishna, N. H., Sridhar, B., Kamal, A., & Nagendra Babu, B. (2018). Regioselective Ring Expansion of Isatins with In Situ Generated α-Aryldiazomethanes: Direct Access to Viridicatin Alkaloids. Organic Letters, 20(12), 3639-3642. https://doi.org/10.1021/acs.orglett.8b01417
Trost, B. M., Kalnmals, C. A., Ramakrishnan, D., Ryan, M. C., Smaha, R. W., & Parkin, S. (2020). Ruthenium-Catalyzed Asymmetric Allylic Alkylation of Isatins. Organic Letters, 22(7), 2584-2589. https://doi.org/10.1021/acs.orglett.0c00504
Varun, Sonam, & Kakkar, R. (2019). Isatin and its derivatives: a survey of recent syntheses, reactions, and applications. MedChemComm, 10(3), 351-368. https://doi.org/10.1039/c8md00585k
Vindya, N. G., Sharma, N., Yadav, M., & Ethiraj, K. R. (2015). Tubulins - the target for anticancer therapy. Curr Top Med Chem, 15(1), 73-82. https://doi.org/10.2174/1568026615666150112115805
Vine, K. L., Locke, J. M., Ranson, M., Pyne, S. G., & Bremner, J. B. (2007). An Investigation into the Cytotoxicity and Mode of Action of Some Novel N-Alkyl-Substituted Isatins. Journal of Medicinal Chemistry, 50(21), 5109-5117. https://doi.org/10.1021/jm0704189
Wang, C., Yan, J., Du, M., Burlison, J. A., Li, C., Sun, Y., . . . Liu, J. (2017). One step synthesis of indirubins by reductive coupling of isatins with KBH4. Tetrahedron, 73(19), 2780-2785. https://doi.org/10.1016/j.tet.2017.03.077
Wang, G., Liu, X., Chen, Y., Yang, J., Li, J., Lin, L., & Feng, X. (2016). Diastereoselective and Enantioselective Alleno-aldol Reaction of Allenoates with Isatins to Synthesis of Carbinol Allenoates Catalyzed by Gold. ACS Catalysis, 6(4), 2482-2486. https://doi.org/10.1021/acscatal.6b00294
Yakan, H., Serdar ÇAvuŞ, M., Kurt, B. Z., MuĞLu, H., SÖNmez, F., & GÜZel, E. (2021). A new series of asymmetric bis-isatin derivatives containing urea/thiourea moiety: Preparation, spectroscopic elucidation, antioxidant properties and theoretical calculations. Journal of Molecular Structure, 130495. https://doi.org/10.1016/j.molstruc.2021.130495
Younis, A. M., Rakha, T. H., El-Gamil, M. M., & El-Reash, G. M. A. (2022). Synthesis and Characterization of Some Complexes Derived from Isatin Dye Ligand and Study of their Biological Potency and Anticorrosive Behavior on Aluminum Metal in Acidic Medium. Journal of Inorganic and Organometallic Polymers and Materials, 32(3), 895-911. https://doi.org/10.1007/s10904-021-02145-4
Yousef, M. A., Ali, A. M., El-Sayed, W. M., Qayed, W. S., Farag, H. H. A., & Aboul-Fadl, T. (2020). Design and synthesis of novel isatin-based derivatives targeting cell cycle checkpoint pathways as potential anticancer agents. Bioorganic Chemistry, 105, 104366. https://doi.org/10.1016/j.bioorg.2020.104366
Yousefi, A., Yousefi, R., Panahi, F., Sarikhani, S., Zolghadr, A. R., Bahaoddini, A., & Khalafi-Nezhad, A. (2015). Novel curcumin-based pyrano[2,3-d]pyrimidine anti-oxidant inhibitors for α-amylase and α-glucosidase: Implications for their pleiotropic effects against diabetes complications. International Journal of Biological Macromolecules, 78, 46-55. https://doi.org/10.1016/j.ijbiomac.2015.03.060
Zhang, C., Li, S., Bureš, F., Lee, R., Ye, X., & Jiang, Z. (2016). Visible Light Photocatalytic Aerobic Oxygenation of Indoles and pH as a Chemoselective Switch. ACS Catalysis, 6(10), 6853-6860. https://doi.org/10.1021/acscatal.6b01969
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Biomedicine and Chemical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
