Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression

Fogaça, Manoela V.; Cândido-Bacani, Priscila de Matos; Benicio, Lucas Milanez; Zapata, Lara Martinelli; Cardoso, Priscilla; Oliveira, Marcelo Tempesta de; Calvo, Tamara Regina; Varanda, Eliana Aparecida; Vilegas, Wagner; Cólus, Ilce Mara de Syllos

doi:10.1080/13880209.2017.1354387

Cited by 14 publications

(5 citation statements)

References 62 publications

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“…Identification of a representative group of isatin-binding proteins suggests that isatin acting on a large number of biological targets can exhibit many biological and potential pharmacological actions. Identification of some isatin responsive genes [22][23][24][25]48,96,97] and various nucleoproteins interacting with this regulator [49,50] opens a new direction in biomedical implications of this compound. Characterization of mechanisms responsible for implementation of isatin actions is especially important in the context of numerous isatin analogues, which are tested as potentially attracting pharmacological tools (e.g., [1][2][3][4][5]).…”

Section: Resultsmentioning

confidence: 99%

“…Thus, taken together, all these results suggest that isatin triggers antiproliferative/apoptotic mechanisms common for different cell types. Since it exhibits cytotoxic and antiproliferative activities and mutagenicity some authors believe that isatin is a good candidate for further research aimed at its potential use as a chemotherapeutic substance .…”

Section: Isatin As An Antitumor Agentmentioning

confidence: 99%

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Isatin, an endogenous nonpeptide biofactor: A review of its molecular targets, mechanisms of actions, and their biomedical implications

et al. 2018

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Isatin (indole-2,3-dione) is an oxidized indole. It is widely distributed in mammalian tissues and body fluids, where isatin concentrations vary significantly from <0.1 to > 10 µM. Isatin output is increased under conditions of stress. Exogenously administered isatin is characterized by low toxicity, mutagenicity, and genotoxicity in vivo. Cytotoxic effects of isatin on various cell cultures are usually observed at concentrations exceeding 100 µM. Binding of [ H]isatin to rat brain sections is consistent with its physiological concentrations. Proteomic analysis of mouse and rat brain isatin-binding proteins revealed about 90 individual proteins, which demonstrated significant interspecies differences (rat versus mouse). Certain evidence exist that redox state(s) and possibly other types of posttranslational modifications regulate affinity of target proteins to isatin. Recent data suggest that interacting with numerous intracellular isatin binding proteins, isatin can act as a regulator of complex protein networks in norm and pathology. Physiological concentrations of isatin in vitro inhibit monoamine oxidase B and natriuretic peptide receptor guanylate cyclase, higher (neuroprotective) concentrations (50-400 μM) cause apoptosis of various (including malignant tumor) cell lines and influence expression of certain apoptosis-related genes. Being administered in vivo, isatin exhibits various behavioral effects; it attenuates manifestations of MPTP-induced parkinsonism and tumor growth in experimental animal models. © 2017 BioFactors, 44(2):95-108, 2018.

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Section: Resultsmentioning

confidence: 99%

Section: Isatin As An Antitumor Agentmentioning

confidence: 99%

Isatin, an endogenous nonpeptide biofactor: A review of its molecular targets, mechanisms of actions, and their biomedical implications

et al. 2018

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“…Studies evaluating the genotoxicity of trypsin inhibitors are scarce. However, considering some studies that also evaluated the potential genotoxic effects but using plant extracts with antimicrobial activity, no genotoxic effect has been observed either 52–55 .…”

Section: Discussionmentioning

confidence: 99%

Prospecting in silico antibacterial activity of a peptide from trypsin inhibitor isolated from tamarind seed

Oliveira

Nascimento

Luz

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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Bacterial infections have become a global concern, stimulating the growing demand for natural and biologically safe therapeutic agents with antibacterial action. This study was evaluated the genotoxicity of the trypsin inhibitor isolated from tamarind seeds (TTI) and the antibacterial effect of TTI theoric model, number 56, and conformation number 287 (TTIp 56/287) and derived peptides in silico . TTI (0.3 and 0.6 mg.mL −1 ) did not cause genotoxicity in cells ( p > 0.05). In silico , a greater interaction of TTIp 56/287 with the Gram-positive membrane (GP) was observed, with an interaction potential energy (IPE) of −1094.97 kcal.mol −1 . In the TTIp 56/287-GP interaction, the Arginine, Threonine (Thr), and Lysine residues presented lower IPE. In molecular dynamics (MD), Peptidotrychyme59 (TVSQTPIDIPIGLPVR) showed an IPE of −518.08 kcal.mol −1 with the membrane of GP bacteria, and the Thr and Arginine residues showed the greater IPE. The results highlight new perspectives on TTI and its derived peptides antibacterial activity.

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“…In fact, this Chinese concoction composed of Radix psudostellariae and Salvia miltiorrhiza, has demonstrated compelling synergistic effects in inducing differentiation of acute promyelocytic leukemia cells in vitro. Additionally, it has shown significant therapeutic activity in murine acute promyelocytic leukemia animal models [58,59] and thus has advanced into clinical trials for treating childhood acute promyeloid leukemia in China [55,57].…”

Section: Classes Of Anticancer Oximesmentioning

confidence: 99%

The Fundamental Role of Oxime and Oxime Ether Moieties in Improving the Physicochemical and Anticancer Properties of Structurally Diverse Scaffolds

Fotie,

Matherne,

Mather

et al. 2023

IJMS

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The present review explores the critical role of oxime and oxime ether moieties in enhancing the physicochemical and anticancer properties of structurally diverse molecular frameworks. Specific examples are carefully selected to illustrate the distinct contributions of these functional groups to general strategies for molecular design, modulation of biological activities, computational modeling, and structure–activity relationship studies. An extensive literature search was conducted across three databases, including PubMed, Google Scholar, and Scifinder, enabling us to create one of the most comprehensive overviews of how oximes and oxime ethers impact antitumor activities within a wide range of structural frameworks. This search focused on various combinations of keywords or their synonyms, related to the anticancer activity of oximes and oxime ethers, structure–activity relationships, mechanism of action, as well as molecular dynamics and docking studies. Each article was evaluated based on its scientific merit and the depth of the study, resulting in 268 cited references and more than 336 illustrative chemical structures carefully selected to support this analysis. As many previous reviews focus on one subclass of this extensive family of compounds, this report represents one of the rare and fully comprehensive assessments of the anticancer potential of this group of molecules across diverse molecular scaffolds.

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Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression

Abstract: IRN and ISA have properties that make them candidates as chemotherapeutics for further pharmacological investigations.

Cited by 14 publications

References 62 publications

Isatin, an endogenous nonpeptide biofactor: A review of its molecular targets, mechanisms of actions, and their biomedical implications

Isatin, an endogenous nonpeptide biofactor: A review of its molecular targets, mechanisms of actions, and their biomedical implications

Prospecting in silico antibacterial activity of a peptide from trypsin inhibitor isolated from tamarind seed

The Fundamental Role of Oxime and Oxime Ether Moieties in Improving the Physicochemical and Anticancer Properties of Structurally Diverse Scaffolds

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