Iodine-catalyzed Synthesis, Antibacterial, and Antioxidant Activity of Isatin Derivatives

Antonius Herry Cahyana(1*), Agus Rimus Liandi(2), Yosua Ongkowidjawa(3)

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok 16424, Indonesia
(2) Department of Chemistry, Faculty of Science and Technology, Syarif Hidayatullah State Islamic University Jakarta, Tangerang Selatan 15412, Indonesia
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok 16424, Indonesia
(*) Corresponding Author


Isatin is a unique compound with many bioactivities such as antiviral, anti-HIV, antitumor, anti-inflammatory, anticonvulsant, and antifungal. In this study, isatin derivatives were synthesized with an iodine catalyst and tested for antibacterial and antioxidant activities. Isatin derivatives were conducted through a Knoevenagel condensation reaction between isatin and malononitrile. The products were confirmed by thin-layer chromatography, melting point apparatus, FTIR, UV-vis spectroscopy, and LC-MS. The optimum reaction conditions were obtained at 10% mol of catalyst, at boiling point ethanol solvent for 30 min. The yield of the isatin derivative products was 71% (3a), 61% (3b), and 67% (3c). The antibacterial activities of the synthesized compounds were weak activity against S. aureus and E. coli. The antioxidant activity test resulted in IC50 values of 266.47, 220.43, and 654.85 ppm for compounds 3a, 3b, and 3c, respectively. The synthesis method using an iodine catalyst in this reaction offers a higher product yield compared to a catalyst-free reaction.


Oxindole derivative; Isatin; Knoevenagel condensation reaction; Antibacterial; Antioxidant.

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[1] Gomtsyan, A., 2012, Heterocycles in drugs and drug discovery, Chem. Heterocycl. Compd., 48 (1), 7–10.

[2] Martins, P., Jesus, J., Santos, S., Raposo, L.R., Roma-Rodrigues, C., Baptista, P.V., and Fernandes, A.R., 2015, Heterocyclic anticancer compounds: Recent advances and the paradigm shift towards the use of nanomedicine’s tool box, Molecules, 20 (9), 16852–16891.

[3] Mishra, P., Mishra, A., Bahe, A.K., Roy, A., and Das, R., 2021, Synthesis of isatin and its derivatives containing heterocyclic compounds, J. Turk. Chem. Soc., Sect. A, 8 (4), 1089–1098.

[4] Borissov, A., Maurya, Y.K., Moshniaha, L., Wong, W.S., Żyła-Karwowska, M., and Stȩpień, M., 2022, Recent advances in heterocyclic nanographenes and other polycyclic heteroaromatic compounds, Chem. Rev., 122 (1), 565–788.

[5] Purbaningtias, T.E., Prasetyoko, D., Bahruji, H., Zein, Y.M., Triwahyono, S., Fadlan, A., and Qoniah, I., 2015, Condensation of indole with isatin over AlCl3/mesoporous aluminosilicate, Indones. J. Chem., 15 (1), 56–63.

[6] Kumar, V., Kaur, K., Gupta, G.K., and Sharma, A.K., 2013, Pyrazole containing natural products: Synthetic preview and biological significance, Eur. J. Med. Chem., 69, 735–753.

[7] Liandi, A.R., Cahyana, A.H., Alfariza, D.N., Nuraini, R., Sari, R.W., and Wendari, T.P., 2024, Spirooxindoles: Recent report of green synthesis approach, Green Synth. Catal., 5 (1), 1–13.

[8] Navaneethgowda, P.V., Bodke, Y.D., Manjunatha, B., and Mussuvir Pasha, K.M, 2022, Benzothiazole-isatin hybrids: Synthesis, characterization, computational and cytotoxic activity studies, J. Mol. Struct., 1266, 133517.

[9] El Malah, T.E., Farag, H., Hemdan, B.A., Abdel Mageid, R.E., Abdelrahman, M.T., El-Manawaty, M.A., and Nour, H.F., 2022, Synthesis, in vitro antimicrobial evaluation, and molecular docking studies of new isatin-1,2,3-triazole hybrids, J. Mol. Struct., 1250, 131855.

[10] Mathur, G., and Nain, S., 2014, Recent advancement in synthesis of ısatin as anticonvulsant agents: A review, Med. Chem., 4 (4), 417–427.

[11] Silva, B.V., Esteves, P.M., and Pinto, A.C., 2011, Chlorination of isatins with trichloroisocyanuric acid, J. Braz. Chem. Soc., 22 (2), 257–263.

[12] Adam, M.S.S., Makhlouf, M.M., Alharbi, A., and El-Metwaly, N.M., 2022, Novel isatin-based complexes of Mn(II) and Cu(II) ions: Characterization, homogeneous catalysts for sulfides oxidation, bioactivity screening and theoretical implementations via DFT and pharmacokinetic studies, J. Mol. Liq., 351, 118620.

[13] Brandão, P., Marques, C., Burke, A.J., and Pineiro, M., 2021, The application of isatin-based multicomponent-reactions in the quest for new bioactive and druglike molecules, Eur. J. Med. Chem., 211, 113102.

[14] Periyasami, G., Karuppiah, P., Stalin, A., Prasad, S., Rahaman, M., Alrehaili, A.A., Al-Dhabi, N.A., and Aldalbahi, A., 2021, Synthesis, absorption, emission and solvatochromic investigation of bioactive isatin tethered acridinedione conjugates, Mater. Today Commun., 26, 102109.

[15] Yagnam, S., Trivedi, R., Krishna, S., Giribabu, L., Praveena, G., and Prakasham, R.S., 2021, Bioactive isatin (oxime)-triazole-thiazolidinedione ferrocene molecular conjugates: Design, synthesis and antimicrobial activities, J. Organomet. Chem., 937, 121716.

[16] Salameh, N., Anastasiou, I., Ferlin, F., Minio, F., Chen, S., Santoro, S., Liu, P., Gu, Y., and Vaccaro, L., 2022, Heterogeneous palladium-catalysed intramolecular C(sp3)[sbnd]H α-arylation for the green synthesis of oxindoles, Mol. Catal., 522, 112211.

[17] Phan Thi Thanh, N., Dang Thi Thu, H., Tone, M., Inoue, H., and Iwasa, S., 2020, Synthesis of oxindole derivatives via intramolecular C–H insertion of diazoamides using Ru(II)-Pheox catalyst, Tetrahedron, 76 (43), 131481.

[18] Gao, K., Kou, L., Fu, R., and Bao, X., 2020, Synthesis of 2-(3-arylallylidene)-3-oxindoles via dirhodium(II)-catalyzed reaction of 3-diazoindolin-2-imines with 1-aryl-substituted allylic alcohols and computational insights, Adv. Synth. Catal., 362 (6), 1292–1297.

[19] Muthusamy, S., Balasubramani, A., and Suresh, E., 2019, Boron trifluoride catalyzed divergent synthesis of 3-alkenyl-3-amino-2-oxindoles and spiro-indeneindolones from propargylic alcohols, Adv. Synth. Catal., 361 (4), 702–707.

[20] Oktavia, S.H., Cahyana, A.H., Hapsari, M., Yunarti, R.T., and Liandi, A.R. 2021, Synthesis and antimicrobial activity of spiro-oxindole-chromene derivative compounds based curcuminoid and chalcone, Rasayan J. Chem., 14 (3), 1990–1997.

[21] Mohamadpour, F., Maghsoodlou, M.T., Lashkari, M., Heydari, R., and Hazeri, N., 2019, Synthesis of quinolines, spiro[4H-pyran-oxindoles] and xanthenes under solvent-free conditions, Org. Prep. Proced. Int., 51 (5), 456–476.

[22] Muthusamy, S., and Ramkumar, R., 2014, Solvent and transition metal-free synthesis of spiro[cyclopropane-1,3-oxindoles] from cyclic diazoamides, Tetrahedron Lett., 55 (47), 6389–6393.

[23] Yaragorla, S., Pareek, A., and Dada, R., 2017, Cycloisomerization of oxindole-derived 1,5-enynes: A calcium(II)-catalyzed one-pot, solvent-free synthesis of phenanthridinones, 3-(cyclopentenylidene)indolin-2-ones and 3-spirocyclic indolin-2-ones, Adv. Synth. Catal., 359 (17), 3068–3075.

[24] Alsaud, N., Shahbaz, K., and Farid, M., 2021, Antioxidant and antibacterial evaluation of Manuka leaves (Leptospermum scoparium) extracted by hydrophobic deep eutectic solvent, Chem. Eng. Res. Des., 174, 96–106.

[25] Ilić, D.P., Troter, D.Z., Stanojević, L.P., Zvezdanović, J.B., Vukotić, D.D., and Nikolić, V.D., 2021, Cranberry (Vaccinium macrocarpon L.) fruit juice from Serbia: UHPLC-DAD-MS/MS characterization, antibacterial and antioxidant activities, LWT, 146, 111399.

[26] Hapsari, M., Cahyana, A.H., Oktavia, S.H., and Liandi, A.R. 2020, Synthesis of spirooxindole-pyrrolizidine compounds using Fe3O4-go catalyst and their bioactivity assays, Rasayan J. Chem., 13 (4), 2317–2324.

[27] Yang, J., Chen, J., Hao, Y., and Liu, Y., 2021, Identification of the DPPH radical scavenging reaction adducts of ferulic acid and sinapic acid and their structure-antioxidant activity relationship, LWT, 146, 111411.

[28] Kayukov, Y.S., Kayukova, O.V., Kalyagina, E.S., Bardasov, I.N., Ershov, O.V., Nasakin, O.E., and Tafeenko, V.A., 2011, Reactions of 2′-oxo-1′,2′-dihydrospiro[cyclopropane-1,3′-indole]-2,2,3,3-tetracarbonitriles with nucleophiles, Russ. J. Org. Chem., 47 (3), 392–401.

[29] Kumar, N.S., Reddy, M.S., Kumar, S.T.S., Bheeram, V.R., Mukkamala, S.B., and Rao, L.C., 2019, A quantitative and rapid knoevenagel condensation catalyzed by recyclable zeolite ımidazole frameworks, ChemistrySelect, 4 (4), 1188–1194.

[30] Lahari, K., and Sundararajan, R., 2020, Design and synthesis of novel isatin derivatives as potent analgesic, anti-inflammatory and antimicrobial agents, J. Chem. Sci., 132 (1), 94.

[31] Jun, M., Fu, H.Y., Hong, J., Wan, X., Yang, C.S., and Ho, C.T., 2003, Comparison of antioxidant activities of isoflavones from kudzu root (Pueraria lobata Ohwi), J. Food Sci., 68 (6), 2117–2122.


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