Synthesis and Evaluation of the Cytotoxic Activities of Some Isatin Derivatives

Reddy, S. Subba; Pallela, Ramjee; Kim, Dong-Min; Won, Mi‐Sook; Shim, Yoon‐Bo

doi:10.1248/cpb.c13-00400

Cited by 10 publications

(4 citation statements)

References 30 publications

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“…Recently, Reddy et al reported the synthesis of chloro/fluoro‐substituted 6‐ N ‐butyl‐6 H ‐indolo[2,3‐ b ]quinoxalines, which exhibited significant in vitro cytotoxic activity against HeLa cells . To the best of our knowledge, the synthesis of bromo‐ and tert ‐butyl‐functionalized indolo[2,3‐ b ]quinoxaline derivatives is still unprecedented.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of New tert‐Butyl‐ and Bromo‐functionalized [1,2,4]Triazino [5,6‐b]indole‐3‐thiols and Indolo[2,3‐b]quinoxalines

Wang

2017

Journal of Heterocyclic Chem

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In the present investigation, the synthesis of a series of structurally new and interesting tert‐butyl‐ and bromo‐functionalized [1,2,4]triazino[5,6‐b]indoles (6a–f) and indolo[2,3‐b]quinoxalines (8a–f) has been achieved, involving the condensation reaction of 7‐bromo‐5‐tert‐butylisatins (4a–f) with thiosemicarbazide (5) and benzene‐1,2‐diamine (7). The substrates 4a–f were prepared through bromination reaction of 5‐tert‐butylisatin (3) with NBS in PEG‐400 followed by alkylation reaction. The molecular structures of these newly synthesized compounds were elucidated on the basis of their elemental analyses and spectral data.

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Section: Resultsmentioning

confidence: 99%

Synthesis of New tert‐Butyl‐ and Bromo‐functionalized [1,2,4]Triazino [5,6‐b]indole‐3‐thiols and Indolo[2,3‐b]quinoxalines

Wang

2017

Journal of Heterocyclic Chem

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“…Isatins have been reported in the literature to possess cytotoxic effects across a range of microorganisms and various cancer cell lines. − The mechanism of cytotoxic action of isatins is unknown, and it is tempting to speculate that one mechanism of cytotoxicity is due to the depletion of AIR resulting in the inhibition of purine biosynthesis. While plausible, the reactivity of isatins with biological sulfhydryl groups complicates the determination of the effect of isatin on purine biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Isatins Inhibit N⁵-CAIR Synthetase by a Substrate Depletion Mechanism

2019

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The continued rise of antibiotic-resistant infections coupled with the limited pipeline of new antimicrobials highlights the pressing need for the development of new antibacterial agents. One potential pathway for new agents is de novo purine biosynthesis as studies have shown that bacteria and lower eukaryotes synthesize purines differently than humans. Microorganisms utilize two enzymes, N 5 -CAIR synthetase and N 5 -CAIR mutase, to convert 5-aminoimidazole ribonucleotide (AIR) into 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) through the intermediate N 5 -carboxy-5-aminoimidazole ribonucleotide (N 5 -CAIR). In contrast, vertebrates directly convert AIR to CAIR via the enzyme AIR carboxylase. A high-throughput screen against N 5 -CAIR synthetase identified a group of compounds with a 2,3-indolinedione (isatin) core that inhibited the enzyme. While initial studies suggested that isatins inhibited the enzyme by a noncompetitive mechanism, here we show that isatins inhibit N 5 -CAIR synthetase by a substrate depletion mechanism. Unexpectedly, we found that isatin reacts rapidly and reversibly with the substrate AIR. The rate of the reaction is dependent upon the substituents on the phenyl moiety of isatin, with 5-and 7-bromoisatin being faster than 4-bromoisatin. These studies suggest that care should be taken when exploring isatin compounds because the biological activity could be a result of their reactivity.

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“…The biological data used in this study was the anti-cancer activity against MCF7, (in terms of -log IC 50 ), of a set of 109 isatin derivatives [43][44][45][46][47][48][49][50][51]. The data set was classified into calibration and prediction set by kenardston algorithm of the 20 prediction molecules from the spaces of the calculated descriptors.…”

Section: Data Setmentioning

confidence: 99%

QSAR and Docking Study of Isatin Analogues as Cytotoxic Agents

Sabet

Khabnadideh

Fathi

et al. 2019

JPRI

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Computational chemistry is a unique method in the drug discovery process?? Explain Why?. In this study 109 molecules containing the isatin backbone were subjected to quantitative structure-activity relationship analysis to find the structure requirements for ligand binding. The structures were sketched and optimized in Hyperchem. The structural invariants used in this study were those obtained from whole molecular structures: by both hyperchem and dragon software (16 types of descriptors). Four chemometrics methods including MLR, FA-MLR, PCR and GA-PLS were employed to make connections between structural parameters and anticancer effects. MLR models revealed the effects of constitutional, functional, geometrical, WHIM and GETAWAY descriptors having higher impact on anticancer activity of the compounds. GA-PLS showed functional, constitutional and chemical descriptor indices to be the most significant parameters on anticancer activity. Moreover, the result of FA-MLR analysis revealed the effects of functional descriptors on the anticancer activity. A comparison between the different statistical methods employed and the results indicated that GA-PLS represented superior results and could explain and predict 81% and JPRI, 27(5): 1-22, 2019; Article no.JPRI.48076 2 78% variances in the PIC 50 data, respectively. Docking studies of these compounds were also investigated and promising results were obtained showing that some compounds were introduced as a good candidate for cancer agents. Original Research Article

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Synthesis and Evaluation of the Cytotoxic Activities of Some Isatin Derivatives

Cited by 10 publications

References 30 publications

Synthesis of New tert‐Butyl‐ and Bromo‐functionalized [1,2,4]Triazino [5,6‐b]indole‐3‐thiols and Indolo[2,3‐b]quinoxalines

Synthesis of New tert‐Butyl‐ and Bromo‐functionalized [1,2,4]Triazino [5,6‐b]indole‐3‐thiols and Indolo[2,3‐b]quinoxalines

Isatins Inhibit N⁵-CAIR Synthetase by a Substrate Depletion Mechanism

QSAR and Docking Study of Isatin Analogues as Cytotoxic Agents

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Synthesis and Evaluation of the Cytotoxic Activities of Some Isatin Derivatives

Cited by 10 publications

References 30 publications

Synthesis of New tert‐Butyl‐ and Bromo‐functionalized [1,2,4]Triazino [5,6‐b]indole‐3‐thiols and Indolo[2,3‐b]quinoxalines

Synthesis of New tert‐Butyl‐ and Bromo‐functionalized [1,2,4]Triazino [5,6‐b]indole‐3‐thiols and Indolo[2,3‐b]quinoxalines

Isatins Inhibit N5-CAIR Synthetase by a Substrate Depletion Mechanism

QSAR and Docking Study of Isatin Analogues as Cytotoxic Agents

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Isatins Inhibit N⁵-CAIR Synthetase by a Substrate Depletion Mechanism