2-Phenylindole derivatives as anticancer agents: synthesis and screening against murine melanoma, human lung and breast cancer cell lines

Gaikwad, Ruchi; Bobde, Yamini; Routholla, Ganesh; Patel, Tarun; Rathore, Anju; Ghosh, Balaram; Das, Kalpataru; Gayen, Shovanlal

doi:10.1080/00397911.2019.1620282

Cited by 9 publications

(2 citation statements)

References 38 publications

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“…Next, we optimized the reaction conditions for compounds 2a,b and 3a,b using different Lewis acids. In our hands, under the previously described reaction conditions (ZnCl 2 /180 °C), we observed the formation of a complex product mixture as concluded from HPLC and 1 H NMR analyses, and unfortunately, the overall yields of the target 2-arylindoles 5a–c did not exceed 10%. Similar results were obtained when the synthesis was performed according to a two-step procedure via isolation of the intermediate hydrazones 4a–c (Scheme , Path B; for analytical data see the Supporting Information).…”

Section: Resultssupporting

confidence: 62%

N-Substituted 5-(1H-Indol-2-yl)-2-methoxyanilines Are Allosteric Inhibitors of the Linoleate Oxygenase Activity of Selected Mammalian ALOX15 Orthologs: Mechanism of Action

et al. 2022

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Here, we describe the first systematic study on the mechanism of substrate-selective inhibition of mammalian ALOX15 orthologs. For this purpose, we prepared a series of N-substituted 5-(1H-indol-2-yl)anilines and found that (N-(5-(1H-indol-2-yl)-2-methoxyphenyl)sulfamoyl)carbamates and their monofluorinated analogues are potent and selective inhibitors of the linoleate oxygenase activity of rabbit and human ALOX15. Introduction of a 2-methoxyaniline moiety into the core pharmacophore plays a crucial role in substrate-selective inhibition of ALOX15-catalyzed oxygenation of linoleic acid at submicromolar concentrations without affecting arachidonic acid oxygenation. Steady-state kinetics, mutagenesis studies, and molecular dynamics (MD) simulations suggested an allosteric mechanism of action. Using a dimer model of ALOX15, our MD simulations suggest that the binding of the inhibitor at the active site of one monomer induces conformational alterations in the other monomer so that the formation of a productive enzyme–linoleic acid complex is energetically compromised.

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Section: Resultssupporting

confidence: 62%

N-Substituted 5-(1H-Indol-2-yl)-2-methoxyanilines Are Allosteric Inhibitors of the Linoleate Oxygenase Activity of Selected Mammalian ALOX15 Orthologs: Mechanism of Action

et al. 2022

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“…Reviewing the synthesis methods of 2-phenylindole compounds over the past two decades is indeed valuable for researchers looking to develop new indole-based drugs. The wide utilization of the 2-phenylindole skeleton in studying anticancer, bacteriostatic, and anti-inflammatory activities underscores its importance in drug discovery and development. ,,− By examination of various synthesis approaches outlined in the literature, researchers can gain insights into efficient and sustainable methods for producing these pharmacologically significant compounds, facilitating the exploration of novel indole-based therapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis on the Synthesis Methods of 2-Phenylindole Derivatives with Pharmacological Importance for Green Synthesis

Wu,

Shen,

Zhao

et al. 2024

Org. Process Res. Dev.

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2-Phenylindoles, as a special subset of indole compounds, stand out as some of the most promising candidates for drug development. To guide researchers toward developing new 2-phenylindole drugs in a more environmentally friendly and costeffective manner, we have summarized and analyzed synthesis methods for 2-phenylindole over the past two decades. Our key findings are as follows: First, among the two methods discussed in this paper, the one-step method is often suitable for the synthesis of 2-phenylindole derivatives with a small amount of substitutions on both sides, whereas the indole C-2 coupling reaction is preferable for indole or C-2 benzene rings with more complex substitutions. Second, the primary challenge in synthesizing 2phenylindole compounds lies in achieving selectivity at the indole C-2 and C-3 sites. Lastly, to achieve more efficient, economical, and environmentally friendly methods, researchers have developed new catalytic systems, including nontoxic catalysts, metal-free catalysts, recyclable metal catalysts, or nanocrystallized transition metals, as well as new methodologies such as photoinduced reactions, electrocatalytic reactions, magnetocatalytic methods, and aqueous-phase catalytic methods. These avenues may represent future research directions for chemists. In conclusion, there remains ample room for research and development in the green synthesis of 2-phenylindole derivatives.

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The application of the Fischer indole synthesis in medicinal chemistry

Seen¹,

Gong²,

Ashton³

2023

Advances in Heterocyclic Chemistry

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2-Phenylindole derivatives as anticancer agents: synthesis and screening against murine melanoma, human lung and breast cancer cell lines

Cited by 9 publications

References 38 publications

N-Substituted 5-(1H-Indol-2-yl)-2-methoxyanilines Are Allosteric Inhibitors of the Linoleate Oxygenase Activity of Selected Mammalian ALOX15 Orthologs: Mechanism of Action

N-Substituted 5-(1H-Indol-2-yl)-2-methoxyanilines Are Allosteric Inhibitors of the Linoleate Oxygenase Activity of Selected Mammalian ALOX15 Orthologs: Mechanism of Action

Comprehensive Analysis on the Synthesis Methods of 2-Phenylindole Derivatives with Pharmacological Importance for Green Synthesis

The application of the Fischer indole synthesis in medicinal chemistry

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