A Review on Biological Active Scaffold Isatin and its Derivatives
Sravanthi Avunoori*
Department of Pharmaceutical Chemistry,
Dr. Gurachar Nargund College of Pharmacy, Muradi, Karnataka, India – 583237.
*Corresponding Author E-mail:
ABSTRACT:
Isatin is an indoledione, a 2,3-diketo derivative figure 1 of indole belonging to the class of indolines. It was first obtained by Erdman and Laurent in 1841 as an oxidation product of indigo dye with nitric acid and chromic acids. It occurs as a natural compound in marine animals and was significantly found in many plants of the genus Isatis, in Couroupita guianensis, and also in humans, as a metabolic derivative of adrenaline and amino acids. Isatin has emerged as a promising scaffold for the design and development of new medicinal agents. Many isatin derivatives have been synthesized on the purpose of achieving effective and selective medicinal agents, with different substituents at any site of its core structure. Numerous reviews on the natural isatins1, synthetic isatin2, synthesis of isatins3,4, reactivity and chemistry of isatins5, biologically active isatin and isatin derivatives have been reported6.
Fig 1: Isatin
NATURAL ISATINS:
Some of the natural isatins include melosatin alkaloids contain methoxy phenyl pentyl isatin a was isolated from Melochia tomentosa, a caribbean tumorigenic plant, 6-(3′-methylbuten-2′-yl) isatin b, a bacterial metabolite was found in Streptomyces albus and 5-(3′-methylbut-2′-yl) isatin c was isolated from Chaetomium globosum. The chemical structures were shown in figure 2.
Fig. 2: Natural Isatins
Synthesis of Isatin:
Many methods have been employed for the synthesis of isatins by utilizing various reagents under variable reaction conditions. Some of the significant synthetic methods have been reported.
Sandmeyer Method:
Most common and the oldest method of synthesis of isatin. It involves condensation between chloral hydrate and a primary arylamine in the presence of hydroxylamine hydrochloride, in aqueous sodium sulfate to form an α‐isonitroso acetanilide followed by subsequent electrophilic cyclization promoted by strong acids (Sandmeyer., 1919)7, the synthetic scheme was depicted in figure 3.
Fig 3: Synthesis of Isatin
Methoxy isatins can also be used for the synthesis of isatin (Stolle method: Stolle.,1922)8, from indoles (Zi. et al., 2014)9, (Bredenkamp. et al., 2015)10, from oxindoles (Wei. et al., 2017)11, (Ying. et al., 2018)12, from acetophenones (Ilangovan. et al., 2014)13, (Ilangovan. et al., 2013)14, (Qian. et al., 2017)15, from 2′-aminophenylacetylenes, 2′-aminostyrenes, and 2′-amino-β-ketoesters (Satish. et al., 2015)16, from α-hydroxy N-arylamides (Li. et al., 2016)17, from α-formyl amides (Yue. et al., 2016)18.
Isatin is considered as one of the significant building blocks in organic synthesis, because of its unique reactive nature19. Aromatic ring (electrophilic aromatic substitution at 5 and 7 position), a ketone 2 and 3 ( nucleophilic addition , chemoselective reductions, oxidations, ring expansions and spioroannulations) and a γ-lactam moiety of isatin (N-substitution) has good reactivity and can be used both as an electrophile and a nucleophile20. Reactivity at 2 and 3 positions of isatin is of significant value which has led to the development of novel compounds with variable biological activities. N-substitution of isatin leads to the substituon at 1 position depicted in figure 421.
Fig 4: N-substitution at 1 position
C2 and C3 substituted derivatives leads to the formation of thiosemicarbazones d (Amna. et al., 2014)22, oxindoles e (Pablo. et al., 2020)23, imines f, hydrazones g, acyl hydrazones h, oximes i, oxidation products j and dimers k which have exhibited the potential biological and pharmacological activities24. The reactivity and the reaction compounds at C2 and C3 are shown in figure 5.
Fig 5: Reactivity at C2 AND C3
Biological Activity of Isatin:
Literature survey suggests that isatin is a versatile scaffold exhibiting tremendous biological and pharmacological properties. (Ajmer singh. et al., 2014) 25 have reviewed the biological activities of various isatin derivatives. Imino isatins have emerged as an important anti-convulsant drugs 26. N-methylisatin-beta-4':4'- diethyl thiosemicarbazone and N-allylisatin-beta-4':4'- diallyl thiosemicarbazone inhibit the production of human immunodeficiency virus (HIV) 27. (5′Z)-5′- (benzylidene) -3′-(4- chlorophenyl) spiro [3H-indole-3,2′-thia-zolidine]-2,4′(1H)-dione and (5′Z)-3′-(4- chlorophenyl) -5′- [4- (1-methylethyl) -benzylidene] spiro [3H-indole-3,2′-thiazolidine]-2,4′(1H)-dione were superior in anticancer activity28. Schiffs bases and mannich bases of isatin was shown to possess superior antimicrobial properties towards different forms of bacteria. Schiff bases of nalidixic acid carbohydrazide and isatin derivatives were synthesized. Anti-TB activity of the synthesized derivatives was investigated against four Mycobacterium strains: Mycobacterium intercellulari, Mycobacterium xenopi, Mycobacterium cheleneo and Mycobacterium smegmatis 29. The structures of the significant biological active isatin were shown in figure 6.
Fig 6: Biological Activities of Isatin
Isatin Schiff Bases:
Schiff bases (–C=N–) carrying imine or azomethine moiety are the important biological compounds and was developed as a versatile pharmacophore building blocks in the design and development of novel biological scaffolds with significant pharmacological activities including antimicrobial, antiviral and anticancer. Isatin-based schiff bases are generally synthesized by condensation of the keto group of isatin with different aromatic primary amines in presence of ethanol, methanol, tetrahydrofuran and 1,2 dichloroethane carrying imine or azomethine (–C=N–) functional group. Isatin schiff bases possesses numerous biological properties like antitumor, antimicrobial, anti-inflammatory, anticonvulsant, antiviral, anti-HIV, antioxidant, CNS depressant activities. Antimicrobial, (Aliasghar.et al., 2007)30 i, (Tayseer. et al., 2020) 31, ia, Antioxidant, (Vairalakshmi. et al., 2019)32 ii, Antibacterial, (Kamaleddin. et al., 2015)33 iii, (Sallam. et al., 2012)34 iiia, (Kamaleddin. et al., 2016)35 iiib, Antiproliferative, (Eman. et al., 2021)36 iv, NSAID (Sheshaiah. et al., 2001)37 v, Anticonvulsant (Hind. et al., 2021)38 vi, activities of the schiffs bases were reported and the structures of the same was depicted in figure 7.
Fig 7: Biologically Active Isatin Schiff Bases
CONCLUSION:
The present review highlights the biological importance of the active scaffold isatin and its various derivatives possessing tremendous activities. The literature reveals that isatin can be transformed into different active compounds which exhibit significant pharmacological activities. Owing to the various synthetic routes brought about by this compound to develop active moieties it became an interest to the chemists, pharmacologists and researchers to create novel isatin derivatives. Many isatin schiff bases can be prepared easily at lower reaction times compared to other derivatives.
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Received on 25.10.2025 Revised on 13.11.2025 Accepted on 28.11.2025 Published on 31.01.2026 Available online from February 07, 2026 Asian J. Research Chem.2026; 19(1):69-72. DOI: 10.52711/0974-4150.2026.00012 ©A and V Publications All Right Reserved
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