Isatin and its derivatives: a survey of recent syntheses, reactions, and applications

Abstract

Isatin (1H-indole-2,3-dione) and its derivatives represent an important class of heterocyclic compounds that can be used as precursors for drug synthesis.

A Series of Isatin-Hydrazones with Cytotoxic Activity and CDK2 Kinase Inhibitory Activity: A Potential Type II ATP Competitive Inhibitor

“…Various substituents on the isatin nucleus displayed numerous biological activities [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ], including antimicrobial activity[ 31 , 37 ], topoisomerase inhibitory activity [ 7 , 38 ], epidermal growth factor receptor (EGFR) inhibitory activity [ 39 ], inhibitory activities on histone deacetylase (HDAC) [ 40 , 41 ], carbonic anhydrase [ 42 , 43 , 44 ], tyrosine kinase [ 45 , 46 , 47 ], cyclin-dependent kinases (CDKs) [ 9 , 48 , 49 ], adenylate cyclase inhibition [ 50 ] and protein tyrosine phosphatase (Shp2) [ 51 ]. A number of isatin-based marketed drugs and potential anticancer agents [ 41 ] are illustrated in Figure 1 . Considering the importance of the development of anticancer therapeutics and the various biological properties of isatin and isatin nucleus-containing derivatives, a series of isatin-hydrazones were designed and synthesized, their cytotoxicities against two different cancer cell lines, namely MCF7 (human breast adenocarcinoma) and A2780 (human ovary adenocarcinoma), were evaluated, their structure–activity relationships (SARs) were studied, their ADME properties were studied using in silico ADME tools and cyclin-dependent kinases 2 inhibitory activities were performed using an enzyme inhibition assay.…”

Recent advances in isatin hybrids as potential anticancer agents

“…[9][10][11][12] Thus, isatin derivatives possess broadspectrum therapeutic properties, such as antibacterial, [12,13] antimalarial, [14,15] antitubercular, [16,17] and anticancer [18][19][20][21][22] activities. Moreover, many anticancer agents such as semaxanib, sunitinib, nintedanib, and hesperadin ( Figure 1) bear an isatin moiety, [23] demonstrating that isatin is a fruitful matrix for the development of novel anticancer drugs.…”

Isatin dimers and their biological activities

“…[ 1 ] Isatin derivatives have the potential to inhibit many enzymes and receptors such as acetylcholinesterase, [ 2 ] butyrylcholinesterase, [ 3 ] carbonic anhydrase, [ 4 ] DNA gyrase, [ 5 ] histone deacetylase, [ 6 ] reverse transcriptase, [ 7 ] serine proteases, [ 8 ] tyrosine kinase, [ 9 ] and tubulin, [ 10 ] so this kind of compound possesses a variety of pharmacological properties. [ 11–16 ] Moreover, various isatin‐containing derivatives such as hesperadin, intedanib, nintedanib, semaxanib, and sunitinib have already been used in the clinical practice, [ 17,18 ] revealing their potential in the development of novel drugs.…”