Isatin–azole hybrids and their anticancer activities

Hou, Yani; Shang, Congshan; Wang, Hui; Yun, Jie

doi:10.1002/ardp.201900272

Cited by 56 publications

(37 citation statements)

References 86 publications

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“…Isatin (1H-indole-2, 3-dione), a precursor for many pharmacologically active compounds, [2][3][4] is an important medicinal chemistry. 5 Isatin derivatives have extensive biological activities, such as antitumor, anti-HIV, antiinflammatory, anti-convulsion, antidepressant, and antifungal effects, 5 attracting much attention.…”

Section: Introductionmentioning

confidence: 99%

<p>The Acetone Indigo Red Dehydrating Agent IF203 Induces HepG2 Cell Death Through Cell Cycle Arrest, Autophagy and Apoptosis</p>

Shang¹,

Wang²,

Li³

et al. 2020

OTT

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Background: Isatin derivatives have extensive biological activities, such as antitumor. IF203, a novel isatin derivative, has not previously been reported to have antitumor activity. Methods: Acid phosphatase assays (APAs) and Ki-67 immunohistochemistry were used to detect the proliferation of HepG2 cells. Transmission electron microscope (TEM) was applied to detect ultrastructural changes. Flow cytometry (FCM) was used to detect cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) of HepG2 cells in vitro. TUNEL, MMP and ROS immunofluorescence assays were applied to assess apoptosis, MMP, and ROS of HepG2 cells in vivo. Western Blotting was applied to assess the levels of apoptosis-and autophagy-related proteins. Results: In this study, in vivo and in vitro experiments showed that IF203 possesses antitumor activity. The results of APAs and Ki-67 immunohistochemistry demonstrated that IF203 could inhibit the proliferation of HepG2 cells. Cell cycle assays, downregulation of Cyclin B1 and Cdc2, and upregulation of P53 suggested that IF203 could lead to G2/M cell cycle arrest. In addition, ultrastructural changes, apoptosis assays, TUNEL immunofluorescence results, upregulated expression of Bax, and downregulated expression of Bcl-2 suggest that IF203 can induce apoptosis in HepG2 cells. After IF203 treatment, intracellular ROS levels increased, MMP decreased, JC-1 green fluorescence was enhanced, and the levels of Caspase-9, Caspase-3 and Cytochrome C expression were upregulated, suggesting that IF203 could induce apoptosis of HepG2 cells through the mitochondrial apoptosis pathway. Moreover, characteristic apoptotic ultrastructural changes were accompanied by the appearance of many autophagy bubbles and upregulation of Atg5, Atg12, ULK1, Beclin-1 and LC3-II proteins, suggesting that IF203 could induce autophagy in HepG2 cells. Conclusion: This study showed that IF203 leads to the death of HepG2 cells through cell cycle arrest, apoptotic induction, and autophagy promotion.

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Section: Introductionmentioning

confidence: 99%

<p>The Acetone Indigo Red Dehydrating Agent IF203 Induces HepG2 Cell Death Through Cell Cycle Arrest, Autophagy and Apoptosis</p>

Shang¹,

Wang²,

Li³

et al. 2020

OTT

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“…These effects are aimed at interruption of pathological links that begin to form after initiation of pathological processes such as MPTP-induced parkinsonism [34,35]. It is possible that some of the recognized proteins and genes sensitive to the neuroprotective dose of isatin may be used as potential targets for numerous analogues synthesized in many laboratories worldwide [81][82][83].…”

Section: Discussionmentioning

confidence: 99%

A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research

Медведев

Kopylov

Buneeva

et al. 2020

IJMS

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Isatin (indole-2,3-dione) is an endogenous regulator, exhibiting a wide range of biological and pharmacological activities. At doses of 100 mg/kg and above, isatin is neuroprotective in different experimental models of neurodegeneration. Good evidence exists that its effects are realized via interaction with numerous isatin-binding proteins identified in the brain and peripheral tissues studied. In this study, we investigated the effect of a single dose administration of isatin to mice (100 mg/kg, 24 h) on differentially expressed proteins and a profile of the isatin-binding proteins in brain hemispheres. Isatin administration to mice caused downregulation of 31 proteins. However, these changes cannot be attributed to altered expression of corresponding genes. Although at this time point isatin influenced the expression of more than 850 genes in brain hemispheres (including 433 upregulated and 418 downregulated genes), none of them could account for the changes in the differentially expressed proteins. Comparative proteomic analysis of brain isatin-binding proteins of control and isatin-treated mice revealed representative groups of proteins sensitive to isatin administration. Control-specific proteins (n = 55) represent specific targets that interact directly with isatin. Appearance of brain isatin-binding proteins specific to isatin-treated mice (n = 94) may be attributed to the formation of new clusters of protein–protein interactions and/or novel binding sites induced by a high concentration of this regulator (ligand-induced binding sites). Thus, isatin administration produces multiple effects in the brain, which include changes in gene expression and also profiles of isatin-binding proteins and their interactomes. Further studies are needed for deeper insight into the mechanisms of the multilevel changes in the brain proteome induced by isatin. In the context of the neuroprotective action, these changes may be aimed at interruption of pathological links that begin to form after initiation of pathological processes.

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“…The pages of the literature is enriched with the glorious achievements of nitrogen-containing heterocycles among them azole is the most remarkable one present in many anticancer drugs such as carboxyamidotriazole, anastrozole, letrozole etc. [37][38][39] Thus, hybridization of quinoline with azole is a prototype for the development of novel anticancer agents that may act against both drug-resistant and drug-sensitive cancers.…”

Section: Quinoline-azole Hybridsmentioning

confidence: 99%

Navigating the Synthesis of Quinoline Hybrid Molecules as Promising Anticancer Agents

Panda

Chakroborty

2020

ChemistrySelect

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The emergence of drug resistance and low specificity with side effects are the significant challenges in pharmaceutical sectors for control of cancer nowadays. Notwithstanding, this is an imperative prerequisite to develop novel anticancer agents through mainstream medicinal chemistry approaches. The intriguing quinoline and its derivatives have demonstrated as significant building blocks for the locating of new promising anticancer agents. Consequently, quinoline moiety with the addition of suitable congeners would offer a strategy for the development of potential drug candidates. This present review article summarizes the recent advances (2018‐2020) of quinoline hybrids and their anticancer activity. The mechanism action and plausible structure‐activity relationship have discussed.

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Isatin–azole hybrids and their anticancer activities

Cited by 56 publications

References 86 publications

<p>The Acetone Indigo Red Dehydrating Agent IF203 Induces HepG2 Cell Death Through Cell Cycle Arrest, Autophagy and Apoptosis</p>

<p>The Acetone Indigo Red Dehydrating Agent IF203 Induces HepG2 Cell Death Through Cell Cycle Arrest, Autophagy and Apoptosis</p>

A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research

Navigating the Synthesis of Quinoline Hybrid Molecules as Promising Anticancer Agents

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