A Mini Review on Isatin, an Anticancer Scaffold with Potential Activities against Neglected Tropical Diseases (NTDs)

Chowdhary, Shefali; Shalini, .; Arora, Amandeep; Kumar, Vipan

doi:10.3390/ph15050536

Cited by 35 publications

(26 citation statements)

References 132 publications

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“…Isatin is also probably one of the most important compounds among the biologically active indoles. In recent years, isatin and isatin-based molecular hybrids have found a variety of applications in pharmacy and drug design [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ].…”

Section: Introductionmentioning

confidence: 99%

New 6′-Amino-5′-cyano-2-oxo-1,2-dihydro-1′H-spiro[indole-3,4′-pyridine]-3′-carboxamides: Synthesis, Reactions, Molecular Docking Studies and Biological Activity

et al. 2023

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The purpose of this work was to prepare new isatin- and monothiomalondiamide-based indole derivatives, as well as to study the properties of the new compounds. The four-component reaction of 5-R-isatins (R = H, CH3), malononitrile, monothiomalonamide (3-amino-3-thioxo- propanamide) and triethylamine in hot EtOH yields a mixture of isomeric triethylammonium 6′-amino-3′-(aminocarbonyl)-5′-cyano-2-oxo-1,2-dihydro-1′H- and 6′-amino-3′-(aminocarbonyl)- 5′-cyano-2-oxo-1,2-dihydro-3′H-spiro[indole-3,4′-pyridine]-2′-thiolates. The reactivity and structure of the products was studied. We found that oxidation of spiro[indole-3,4′-pyridine]-2′-thiolates with DMSO-HCl system produced only acidification products, diastereomeric 6′-amino-5′-cyano-5-methyl-2-oxo-2′-thioxo-1,2,2′,3′-tetrahydro-1′H-spiro-[indole-3,4′-pyridine]- 3′-carboxamides, instead of the expected isothiazolopyridines. The alkylation of the prepared spiro[indole-3,4′-pyridine]-2′-thiolates upon treatment with N-aryl α-chloroacetamides and α-bromoacetophenones proceeds in a regioselective way at the sulfur atom. In the case of α-bromoacetophenones, ring-chain tautomerism was observed for the S-alkylation products. According to NMR data, the compounds consist of a mixture of stereoisomers of 2′-amino-6′-[(2-aryl- 2-oxoethyl)thio]-3′-cyano-2-oxo-1′H-spiro[indoline-3,4′-pyridine]-5′-carboxamides and 5′-amino- 3′-aryl-6′-cyano-3′-hydroxy-2-oxo-2′,3′-dihydrospiro[indoline-3,7′-thiazolo[3,2-a]pyridine]-8′-carboxamides in various ratios. The structure of the synthesized compounds was confirmed by IR spectroscopy, HRMS, 1H and 13C DEPTQ NMR studies and the results of 2D NMR experiments (1H-13C HSQC, 1H-13C HMBC). Molecular docking studies were performed to investigate suitable binding modes of some new compounds with respect to the transcriptional regulator protein PqsR of Pseudomonas aeruginosa. The docking studies revealed that the compounds have affinity for the bacterial regulator protein PqsR of Pseudomonas aeruginosa with a binding energy in the range of −5.8 to −8.2 kcal/mol. In addition, one of the new compounds, 2′-amino-3′-cyano-5-methyl- 2-oxo-6′-{[2-oxo-2-(p-tolylamino)ethyl]thio}-1′H-spiro-[indoline-3,4′-pyridine]-5′-carboxamide, showed in vitro moderate antibacterial effect against Pseudomonas aeruginosa and good antioxidant properties in a test with 1,1-diphenyl-2-picrylhydrazyl radical. Finally, three of the new compounds were recognized as moderately active herbicide safeners with respect to herbicide 2,4-D in the laboratory experiments on sunflower seedlings.

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Section: Introductionmentioning

confidence: 99%

New 6′-Amino-5′-cyano-2-oxo-1,2-dihydro-1′H-spiro[indole-3,4′-pyridine]-3′-carboxamides: Synthesis, Reactions, Molecular Docking Studies and Biological Activity

et al. 2023

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“…The thiosemicarbazone linkage group, >N−C(=S)NH−NN−, was attached to isatin ring, usually by condensation reaction of different thiosemicarbazides with isatins to produce corresponding isatin β‐thiosemicarbazones. These compounds of isatins have been extensively synthesized, possessing many interesting biological activities, either due to the activity of the isatin ring itself, or from new organic frameworks attached to this linkage group along with isatin ring, as mentioned above [17] . They are also widely used as ligands in complex chemistry [23] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Potential Dual Inhibitory Activity Against Acetylcholinesterase and Butyrylcholinesterase of Galactose‐Conjugated Isatin β‐Thiosemicarbazones

et al. 2023

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A series of different isatin-thiosemicarbazones 4 a-4 t derived from corresponding substituted isatins and N- (2,3,4,thiosemicarbazide had been synthesized. Their anti-Alzheimer activity were studied through the inhibitions of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of these compounds exhibited inhibitory activities against these enzymes. Of these isatin N- (2,3,4,6-tetra-O-acetyl-β-d-galactoranosyl)thiosemicarbazones 4 a-4 t, in IC 50 range below 0.05 μM, some thiosemicarbazones exhibited potent inhibitory activity against AChE enzyme, including 4 s (1-benzyl) > 4 t (1-phenthyl) > 4 p (1-allyl) > 4 r (1-t-butyl), and others exhibited potent inhibitory activity against BChE, including 4 t (1-phenthyl) > 4 o (1-propyl) > 4 q (1-butyl) > 4 s (1-benzyl). Enzymic kinetics of AChE and BChE inhibition of 4 s and 4 t, were studied. These compounds with strong inhibitory activity had been further investigated in induced fit docking studies as well as molecular dynamics simulations. The obtained resulting simulations indicate that strong ligandresidues interactions were decisive factors to inhibitory activity of 4 s and 4 t against AChE and BChE enzymes, respectively.

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“…Isatin is found in numerous naturally occurring substances, including marine natural products, alkaloids, and fungal metabolites, in addition to being endogenously present in mammalian tissues and fluids, including those of humans and other mammals [21]. Isatin nucleus represents a versatile scaffold for chemical modifications, where its derivatives disclosed diverse pharmacological actions for the treatment of diverse diseases and disorders [21][22][23][24][25][26][27]. Isatin-tethered molecules such as nintedanib, sunitinib, semaxanib, and orantinib have either received clinical approval (nintedanib and sunitinib) or are currently the subject of clinical trials (semaxanib and orantinib) [28,29].…”

Section: Introductionmentioning

confidence: 99%

Development of Novel Isatin-Tethered Quinolines as Anti-Tubercular Agents against Multi and Extensively Drug-Resistant Mycobacterium tuberculosis

et al. 2022

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We describe the design and synthesis of two isatin-tethered quinolines series (Q6a–h and Q8a–h), in connection with our research interest in developing novel isatin-bearing anti-tubercular candidates. In a previous study, a series of small molecules bearing a quinoline-3-carbohydrazone moiety was developed as anti-tubercular agents, and compound IV disclosed the highest potency with MIC value equal to 6.24 µg/mL. In the current work, we adopted the bioisosteric replacement approach to replace the 3,4,5-trimethoxy-benzylidene moiety in the lead compound IV with the isatin motif, a privileged scaffold in the TB drug discovery, to furnish the first series of target molecules Q6a–h. Thereafter, the isatin motif was N-substituted with either a methyl or benzyl group to furnish the second series Q8a–h. All of the designed quinoilne-isatin conjugates Q6a–h and Q8a–h were synthesized and then biologically assessed for anti-tubercular actions towards drug-susceptible, MDR, and XDR strains. Superiorly, the N-benzyl-bearing compound Q8b possessed the best activities against the examined M. tuberculosis strains with MICs equal 0.06, 0.24, and 1.95 µg/mL, respectively.

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A Mini Review on Isatin, an Anticancer Scaffold with Potential Activities against Neglected Tropical Diseases (NTDs)

Cited by 35 publications

References 132 publications

New 6′-Amino-5′-cyano-2-oxo-1,2-dihydro-1′H-spiro[indole-3,4′-pyridine]-3′-carboxamides: Synthesis, Reactions, Molecular Docking Studies and Biological Activity

New 6′-Amino-5′-cyano-2-oxo-1,2-dihydro-1′H-spiro[indole-3,4′-pyridine]-3′-carboxamides: Synthesis, Reactions, Molecular Docking Studies and Biological Activity

Synthesis and Potential Dual Inhibitory Activity Against Acetylcholinesterase and Butyrylcholinesterase of Galactose‐Conjugated Isatin β‐Thiosemicarbazones

Development of Novel Isatin-Tethered Quinolines as Anti-Tubercular Agents against Multi and Extensively Drug-Resistant Mycobacterium tuberculosis

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