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

Varun, _; Sonam, -; Kakkar, Rita

doi:10.1039/c8md00585k

Cited by 261 publications

(128 citation statements)

References 131 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Isatin derivatives potentially act on various biological targets. In this article, a series of novel isatin-hydrazones were synthesized in excellent yields. Their cytotoxicity was tested against human breast adenocarcinoma (MCF7) and human ovary adenocarcinoma (A2780) cell lines using MTT assay. Compounds 4j (IC50 = 1.51 ± 0.09 µM) and 4k (IC50 = 3.56 ± 0.31) showed excellent activity against MCF7, whereas compound 4e showed considerable cytotoxicity against both tested cell lines, MCF7 (IC50 = 5.46 ± 0.71 µM) and A2780 (IC50 = 18.96± 2.52 µM), respectively. Structure-activity relationships (SARs) revealed that, halogen substituents at 2,6-position of the C-ring of isatin-hydrazones are the most potent derivatives. In-silico absorption, distribution, metabolism and excretion (ADME) results demonstrated recommended drug likeness properties. Compounds 4j (IC50 = 0.245 µM) and 4k (IC50 = 0.300 µM) exhibited good inhibitory activity against the cell cycle regulator CDK2 protein kinase compared to imatinib (IC50 = 0.131 µM). A molecular docking study of 4j and 4k confirmed both compounds as type II ATP competitive inhibitors that made interactions with ATP binding pocket residues, as well as lacking interactions with active state DFG motif residues.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…[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.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in isatin hybrids as potential anticancer agents

Ding

Zhou

Zeng

2020

Archiv der Pharmazie

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The isatin framework is a useful template for the development of novel anticancer agents. This is exemplified by the fact that several isatin‐based anticancer agents, such as semaxanib, sunitinib, nintedanib, and hesperadin, are already in use or under clinical trials for the treatment of diverse kinds of cancers. Isatin‐based hybrids could be obtained by incorporating other anticancer pharmacophores into the isatin skeleton and they have the potential to overcome drug resistance with reduced side effects. Thus, isatin‐based hybrids may provide attractive scaffolds for the development of novel anticancer agents. This review covers the recent advances of isatin‐based hybrids with anticancer activity, covering articles published between 2001 and 2019. The anticancer activities of these molecules and the structure–activity relationships are also discussed. The purpose of this review article is to set up the direction for the design and development of isatin‐based hybrids with high efficacy and low toxicity.

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“…[ 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.…”

Section: Introductionmentioning

confidence: 99%

Isatin dimers and their biological activities

Zhang

Liu

et al. 2020

Archiv der Pharmazie

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Dimerization is a promising strategy to develop novel drug candidates that could extend the biological spectrum, enhance the activity, overcome drug resistance, as well as improve pharmacological, pharmacokinetic, and physicochemical profiles. Isatin dimers possess a broad spectrum of biological properties and the isatin dimer indirubin has already been used in the clinic, revealing the potential of isatin dimers as putative drugs. This review covers the recent advances of isatin dimers as pharmacologically significant scaffolds and the structure–activity relationship to set up the direction for the design and development of isatin dimers with higher efficiency and lower toxicity.

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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.

Cited by 261 publications

References 131 publications

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

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

Recent advances in isatin hybrids as potential anticancer agents

Isatin dimers and their biological activities

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