A mini review on synthesis and biological activities of isatin derivatives

Mohammad Asif


Isatin is an indole derivative and important class of heterocyclic compounds. Isatin derivatives are used for the synthesis of a large variety of heterocyclic compounds and drug synthesis. Isatin derivatives have attracted strong interest in medicinal chemistry due to their potent biological activities. Isatin and its derivatives possess various biological activities such as anticancer, antimicrobial, antiviral, anti-tubercular, anthelmintic, anti-HIV, anti-inflammatory, analgesic, antiepileptic, antioxidant and other biological activities. This review outlines some common used methods to synthesize the isatin derivatives, with advances in the use of isatin derivatives for its biological properties.


Isatin; Antibacterial; Anticancer, Analgesic; Anti-inflammatory;Antioxidants.

Full Text:



. Da Silva JFM, Garden SJ, Pinto AC, The chemistry of isatins: a review from 1975 to 1999. J Brazil Chem Soc, 2001; 12(3): 273-324.

. Pal M, Sharma NK, Priyanka, Jha KK, Synthetic and biological multiplicity of isatin: A Review. J Adv Sci Res, 2011; 2(2): 35-44.

. Bhrigu B, Pathak D, Siddiqui N, Alam MS, Ahsan W, Search for biological active isatins: a short review. Inter J Pharm Sci & Drug Res, 2010; 2(4): 229-235.

. Ratnamala P. Sonawane RP, Rahul R. Tripathi RR, The chemistry and synthesis of 1H-indole-2,3-dione (Isatin) and its derivatives. Inter Lett Chem, Physics & Astron, 2013; 7(1): 30-36.

. Pakravan P, Kashanian S, Khodaei MM, Harding FJ, Biochemical and pharmacological characterization of isatin and its derivatives: from structure to activity. Pharmacol Reports, 2013; 65(2): 313-335.

. Chhajed SS, Padwal MS, Antimicrobial Evaluation of Some novel Schiff and Mannich bases of Isatin and its derivatives with quinolin. Inter J ChemTech Res, 2010; 2(1): 209-213.

. Shmidt MS, Reverdito AM, Kremenchuzky L, Perillo IA, Blanco MM, Simple and efficient microwave assisted N-alkylation of isatin. Molecules, 2008; 13(4): 831-840.

. Sriram D, Bal TR, Yogeeswari P, Synthesis, antiviral and antibacterial activities of isatin mannich bases. Med Chem Res, 2005; 14(4): 211-228.

. Ramachandran S, Raju KNK, Synthesis, Characterization and In-Vitro Anti-Microbial Screening of Novel Schiff Bases of Isatin Derivatives. Asian J Res Chem, 2011; 4(6): 925-927.

. Lashgari N, Ziarani GM, Synthesis of heterocyclic compounds based on isatin through 1,3-dipolar cycloaddition reactions, Reviews and Accounts. Arkivoc, 2012(1): 277-300.

. Manna K, Aggarwal Y. Microwave assisted synthesis of new indophenazine 1,3,5-trisubstituted pyrrazoline derivatives of benzofuran and their antimicrobial activity. Bioorg. Med. Chem. Lett. 2009; 19: 2688-2692.

. Pandeya SN, Kumar R, Pathak AK, Nath G. Synthesis and biological evaluation of triazine derivatives. Der Pharm. Chem.2010; 2(2): 257-266.

. Rahman AHA, Keshk EM, Hanna MA. Synthesis and evaluation of some new spiroindoline based hetrocycles as potentially active antimicrobial. Bioorg. Med. Chem. 2004; 12: 2483-2488.

. Singh GS, Luntha P. Synthesis and antimicrobial activity of new 1-alkyl/cyclohexyl-3, 3-diaryl-1’-methylspiro [azetidine-2, 3’-indoline]-2’, 4-diones. Eur. J. Med. Chem. 2009; 44: 2265-2269.

. Patel A, Bari S, Talele G, Patel J. Synthesis and antimicrobial activity of some new isatin derivatives. Iran. J. Pharm. Res. 2006; 4:249-254.

. Pardasani RT, Pardasani P, Muktawat S, Chaturvedi V. Reaction of 2-thiozoline-2-thiol with isatin derivatives. Phosp. Silic. Sulp.1998; 142: 221-227.

. Olomola TO, Bada DA. Synthesis and antibacterial activity of two spiro [indole] thiadiazole derivatives. Toxi. Environ. Chem.2009; 91(5):941-946.

. Pandeya SN, Sriram D, Nath G. Synthesis, antibacterial, antifungal and anti-HIV activity of norfloxacin mannich bases Eur. J. Med. Chem.2000; 35: 249-255.

. Vine KL, Locke JM, Ronson M. In vitro cytotoxicity evaluation of some substituted isatin derivatives. Bioorg. Med. Chem.2007; 15: 931-938.

. Solomon VR, Lee C, Hu H. Hybrid pharmacophore design and synthesis of isatinbenzothiazole analogs for their anti-breast cancer activity. Bioorg. Med. Chem. 2009; 17: 7585-7592.

. Wee XK, Yeo WK, Zhang B, Tan VBC. Synthesis and evaluation of functionalized isoindigo as antiproliferative agents. Bioorg. Med. Chem. 2009; 17: 7562-7561.

. Ge P, Kalwan TI. Design and Synthesis of 3,5-dialkylamino substituted 8H, 10H-3(R), 15b(S)-2,3,6,7-tetrahydro-1,5,3-dioxoazepino[3,2-c]indolo[3,2-g]pteridine-7-ones. Bioorg. Med. Chem. Lett.1997; 7(23): 3023-3026.

. Shibinskya MO, Lyakhov SA, Mazepa AV, Andronati SA. Synthesis, Cytotoxicity, Antiviral activity and interferon inducing ability of 6-(2-aminomethyl)-6H-indolo [2, 3-b] quinoxalines. Eur. J. Med.Chem. 2010; 45: 1237-1243.

. Chen LR, Wang YC, Lin YW, Chou SY, Chen SF. Synthesis and evaluationof isatin derivatives as effective SARS Coronavirus 3CL protease inhibitors. Bioorg. Med. Chem. Lett. 2005; 15: 3058-3062.

. Andrieu BM, Merour JY. Reaction of 3-([(triflouromethyl) sulfonyl] oxy)-1H –indole derivatives with diamines and carbon nucleophiles, synthesis of 6H-indolo [2, 3-b] quinoxaline derivatives. Tetrahedron. 1998; 54: 11095-11110.

. Sin Ny, Venables BL, Combrink KD, Gulgeze HB, Yu KL, Civiello RL. Respiratory, syncytial virus fusion inhibitors part 7, structure activity relationship with a series of isatin oximes that demonstrate antiviral activity invivo. Bioorg. Med. Chem. Lett. 2009; 19:4857-4862.

. Sriram D, Yogeeswari P, Gopal G. Synthesis, anti HIV and antitubercular activity of lamivudine prodrugs. Eur. J. Med. Chem. 2005; 40:1373-1376.

. Oliveira MRP, Torres SC, Garden SV, Santos CVB, Alves TR. Synthesis and antiviral evaluation of isatin Ribonucleosides. Nucle. Nucleio. Nucleic acid. 2002; 11(12): 825-835.

. Palluotto F, Carotti A, Casini G, Camagna F, Genchi G. Structure activity relationship of 2-aryl-2, 5 dihydropyridazino [4,3-b] indol-3(3H)-ones at the benzodiazepine receptor. Bioorg. Med. Chem .1996; 4(12): 2091-2104.

. Campagna F, Carotti A, Casini G, Palluotto F, Genchi G, Sarro GBD. 2-Aryl-2,5-dihydropyridazino[4,3-b] indol-3(3H) ones. Bioorg. Med. Chem.1993; 1(6): 437-446.

. Ragavendran JV, Sriram D, Patel SK, Reddy IV, Bhathwajan N. Design and synthesis and anticonvulsant activity from a combined phthalamide-GABA-anilide and hydrazone pharmacophore. Eur. J. Med. Chem.2007; 42: 146-151.

. Sridhar SK, Pandeya SN, Stables JP, Ramesh A. Anticonvulsant activity of hydrazones, Schiff and mannich bases of isatin derivatives. Eur. J. Pharm. Sci. 2002; 16: 129-132.

. Raj M, Veerasamy N, Singh VK. Highly enantioselective synthesis of 3-cycloalkanone-3-hydroxy-2-oxindoles, potential anticonvulsants. Tetrah. Lett. 2010; 51: 2157-2159.

. Panneerselvam P, Reddy RS, Murali K, Kumar NR. Synthesis, analgesic, anti-inflammatory, and antimicrobial activities of 5-sustituted isatin derivatives. Der Pharm. Chem. 2010; 2(1): 28-37.

. Matheus ME, Violante FDA, Garden SJ, Pinto AC. Isatin inhibit cyclooxygenase-2 and inducible nitric oxide synthase in a mouse macrophage cell-line. Eur. J. Pharmcol. 2007; 556: 200-206.

. Chiyanzu I, Clarkson C, Smith PJ, Lehman J. Design, synthesis and anti-plasmodial evaluation in vitro of new 4-aminoquinoline isatin derivatives. Bioorg. Med. Chem. Lett. 2005; 13: 3249-3261.

. Kumar SP, Gut J, Guedes R, Rosenthal P, Santos MMM, Moreira R. Design, synthesis and evaluation of 3-methylene-substituted indolinones as antimalarials. Eur. J. Med. Chem. 2011; 46: 927-933.

. Sriram D, Yogeeswari P, Gopal G. Synthesis, anti-HIV and antitubercular activities of lamivudine prodrugs. Eur. J. Med. Chem. 2005; 40: 1373-1376.

. Aboul-Fadl T, Bin-Jubair FAS, Aboul-Wafa O. Schiff bases of indoline-2,3-dione (isatin) derivatives and nalidixic acid carbohydrazide, synthesis, antitubercular activity and pharmacophoric model building. Eur. J. Med. Chem. 2010; 45: 4578-4586.

. Kumar RS, Rajesh SM, Perumal S, Banerjee D, Yogeeswari P, Sriram D. Novel three-component domino reactions of ketones, isatin and amino acids: Synthesis and discovery of antimycobacterial activity of highly functionalized novel dispiropyrrolidines. Eur. J. Med. Chem. 2010; 45:411–422.

. Andreani A, Burnelli S, Granaiola M, Leoni A. New isatin derivatives with antioxidant activity. Eur. J. Med. Chem. 2010; 45: 1374-1378.

. Bal TR, Anand B, Yogeeswari P, Sriram D. Synthesis and evaluation of anti-HIV activity of isatin β-thiosemicarbazone derivatives. Bioorg. Med. Chem. Lett 2005; 15: 4451-4455.

. Kumari G, Modi NM, Gupta SK, Singh RK. Rhodium (II) acetate-catalyzed stereoselective synthesis, SAR and anti-HIV activity of novel oxindoles bearing cyclopropane ring. Eur. J. Med. Chem. 2011; 46: 1181-1188.

. Banerjee D, Yogeeswari P, Bhat P, Thomas A, Srividya M, Sriram D. Novel isatinyl thiosemicarbazones derivatives as potential molecule to combat HIV-TB co-infection. Eur. J. Med. Chem. 2011; 46:106-121.

. Wang Z. Comprehensive Organic Name Reactions and Reagents. 3rd edition. Wiley-Interscience; 2009.

. Hossain MM, Ferdous NN, Muhib MH, et al. The effect of deactivating groups in the formation of some biologically important lactams (Isatins) and their further derivatization. J Bangladesh Chem Soc, 2012; 25(1): 46-52.

. Sumpter WC, The Chemistry of Isatin, Chem Rev, 1944; 34(3): 393-434.

. Li JJ. Name Reactions in Heterocyclic Chemistry II. John Wiley & Sons; 2011.

. Viramgama P, Synthesis and Reactivity of New versatile Heterocyclic compound Izatin and its derivativesr. Ind J Appl Res, 2012; 2(3): 9-11.

. Matesic L, Locke JM, Vine K, Ranson M, Bremner JB, Skropeta D, Synthesis and anti-leukaemic activity of pyrrolo[3,2,1-hi]indole-1,2- diones, pyrrolo[3,2,1-ij]quinoline-1,2-diones and other polycyclic isatin derivatives. Tetrahedron, 2012; 68(34): 6810-6819.

. Gassman PG, Cue BW, Luh TY, A general method for the synthesis of isatins. The J Org Chem, 1977; 42(8): 1344-1348.

. Wakchaure ND, Shejwal SS, Deshmukh VK, Chaudhari SR, Review on Common Methods to Synthesize Substituted1H-Indole-2, 3-Dione (Isatin) Derivatives and Their Medicinal Significance. Am J PharmTech Res, 2012; 2(4): 288-310.

. Chinnasamy RP, Sundararajan R, Govindaraj S, Synthesis, characterization, and analgesic activity of novel schiff base of isatin derivatives. J Adv Pharm Tech & Res, 2010; 1(3): 342-347.

. Panneerselvam P, Reddy RS, Murali K, Kumar RR, Synthesis, analgesic, anti-inflammatory and antimicrobial activities of some novel Schiff’s bases of 5-subsituted Isatin. Der Pharma Chemica, 2010; 2(1): 28-37.

. Venkateshwarlu E, Venkateshwar RJ, Umasankar K, Dheeraj G, Study of anti-inflammatory, analgesic and antipyretic activity of novel isatin derivatives. Asian J Pharm & Clin Res, 2012; 5(4): 187-190.

. Hans RH, Wiid IJ, van Helden PD, et al. Novel thiolactone-isatin hybrids as potential antimalarial and antitubercular agents. Bioorg & Med Chem Lett, 2011; 21(7): 2055-2058.

. Raj R, Singh P, Singh P, Gut J, Rosenthal PJ, Kumar V, Azide-alkyne cycloaddition en route to 1H-1,2,3-triazole-tethered 7-chloroquinoline-isatin chimeras: synthesis and antimalarial evaluation. Euro J Med Chem, 2013; 62: 590-596.

. Chiyanzu I, Clarkson C, Smith PJ, Lehman J, Design, synthesis and anti-plasmodial evaluation in vitro of new 4-aminoquinoline isatin derivatives. Bioorg & Med Chem Lett, 2005; 13(9): 3249-3261.

. Andreani A, Burnelli S, Granaiola M, et al. New isatin derivatives with antioxidant activity. Eur J Med Chem, 2010: 45(4): 1374-1378.

. Kiran G, Maneshwar T, Rajeshwar Y, Sarangapani M, Microwave-Assisted Synthesis, Characterization, Antimicrobial and Antioxidant Activity of Some New Isatin Derivatives. J Chem, 2013, Article ID 192039, 7 pages, 2013. doi:10.1155/2013/192039.


  • There are currently no refbacks.

Copyright (c) 2017 Mohammad Asif

@2016 by Universal Publishing & Research Organization

For any Technical Support contact us at editor@uproonline.com, editorupro@gmail.com