Identification of new 3-phenyl-1H-indole-2-carbohydrazide derivatives and their structure–activity relationships as potent tubulin inhibitors and anticancer agents: A combined in silico, in vitro and synthetic study

Saruengkhanphasit, Rungroj; Butkinaree, Chutikarn; Ornnork, Narittira; Lirdprapamongkol, Kriengsak; Niwetmarin, Worawat; Svasti, Jisnuson; Ruchirawat, Somsak; Eurtivong, Chatchakorn

doi:10.1016/j.bioorg.2021.104795

Cited by 14 publications

(17 citation statements)

References 57 publications

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“…Among the synthesized compounds, St.30 ( Figure 7 ) was able to induce cell cycle arrest at the G2/M phase on A549 cancer cell line. Additionally, this structure also exhibited tubulin polymerization inhibitory activities, whereas when the bromine substitution was added to indole ring and methoxy on furan ring ( St.31 ; Figure 7 ) and the anticancer activities were better than St.30 with IC 50 value under 0.5 μM against HuCCA-1 and HepG2 cancer cell lines [ 92 ].…”

Section: Indole Analoguesmentioning

confidence: 99%

Recent Advances of Tubulin Inhibitors Targeting the Colchicine Binding Site for Cancer Therapy

Hawash

2022

Biomolecules

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Cancer accounts for numerous deaths each year, and it is one of the most common causes of death worldwide, despite many breakthroughs in the discovery of novel anticancer candidates. Each new year the FDA approves the use of new drugs for cancer treatments. In the last years, the biological targets of anticancer agents have started to be clearer and one of these main targets is tubulin protein; this protein plays an essential role in cell division, as well as in intracellular transportation. The inhibition of microtubule formation by targeting tubulin protein induces cell death by apoptosis. In the last years, numerous novel structures were designed and synthesized to target tubulin, and this can be achieved by inhibiting the polymerization or depolymerization of the microtubules. In this review article, recent novel compounds that have antiproliferation activities against a panel of cancer cell lines that target tubulin are explored in detail. This review article emphasizes the recent developments of tubulin inhibitors, with insights into their antiproliferative and anti-tubulin activities. A full literature review shows that tubulin inhibitors are associated with properties in the inhibition of cancer cell line viability, inducing apoptosis, and good binding interaction with the colchicine binding site of tubulin. Furthermore, some drugs, such as cabazitaxel and fosbretabulin, have been approved by FDA in the last three years as tubulin inhibitors. The design and development of efficient tubulin inhibitors is progressively becoming a credible solution in treating many species of cancers.

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Section: Indole Analoguesmentioning

confidence: 99%

Recent Advances of Tubulin Inhibitors Targeting the Colchicine Binding Site for Cancer Therapy

Hawash

2022

Biomolecules

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“…The synthesized compounds were docked with the CBS of tubulin protein and indole ring was found to occupy the hydrophobic pockets of the active site. [63] 2. Compounds 53 and 54 were found with the most potent activity, with IC 50 values from 10 to 15 μM (Figure 11).…”

Section: -Phenyl-1h-indole-2-carbohydrazide Derivativesmentioning

confidence: 99%

“…The synthesized compounds were docked with the CBS of tubulin protein and indole ring was found to occupy the hydrophobic pockets of the active site. [ 63 ]…”

Section: Indole Derivatives As Potent Inhibitors Of Cbsmentioning

confidence: 99%

Indole derivatives targeting colchicine binding site as potential anticancer agents

Goel

Jaiswal

Jain

2023

Archiv der Pharmazie

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Microtubules are appealing as intracellular targets for anticancer activity due to their importance in cell division. Three important binding sites are present on the tubulin protein: taxane, vinca, and colchicine binding sites (CBS). Many USFDA‐approved drugs such as paclitaxel, ixabepilone, vinblastine, and combretastatin act by altering the dynamics of the microtubules. Additionally, a large number of compounds have been synthesized by medicinal chemists around the globe that target different tubulin binding sites. Although CBS inhibitors have proved their cytotoxic potential, no CBS‐targeting drug had been able to reach the market. Several studies have reported design, synthesis, and biological evaluation of indole derivatives as potential anticancer agents. These compounds have been shown to inhibit cancer cell proliferation, induce apoptosis, and disrupt microtubule formation. Moreover, the binding affinity of these compounds to the CBS has been demonstrated using molecular docking studies and competitive binding assays. The present work has reviewed indole derivatives as potential colchicine‐binding site inhibitors. The structure–activity relationship studies have revealed the crucial pharmacophoric features required for the potent and selective binding of indole derivatives to the CBS. The development of these compounds with improved efficacy and reduced toxicity could potentially lead to the development of novel and effective cancer therapies.

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“…Molecular docking studies, predicted that indole derivatives 11–13 (Figure 6) inhibited colchicine binding and formed hydrogen bonds and hydrophobic interactions with protein residues that contributed to perturbing microtubule dynamics. As determined by the tubulin polymerization assay, bromine substitution at C5 was the most favorable [40] …”

Section: Carbohydrazide Substituted Indole Derivativesmentioning

confidence: 99%

“…As determined by the tubulin polymerization assay, bromine substitution at C5 was the most favorable. [40]…”

Section: Chemistryselectmentioning

confidence: 99%

Indole Derived Anticancer Agents

et al. 2022

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Indole moiety is a magnificent nucleus in the development of anticancer drugs. The pharmacological profile of indole is excellent in targeting a wide range of proteins, enzymes. An indole has a nitrogen atom that is capable of forming hydrogen bonds with the targets emphasizing its potential. Many studies have demonstrated the effectiveness of indole in the treatment of cancer by working through various pathways. Indole-based drugs got market approval to be used as chemotherapeutics, such as vincristine and vinblastine which encourage researchers to work on indole derivatives for cancer treatment with a better pharmacokinetic profile. This prompted us to review on indole derivatives as anticancer agents to bring out their potential derivatives under study. This study encompasses literature published between 2014 and 2021 on indole scaffold that exhibits in vitro and in vivo potential against cancer by searching PubMed, Google Scholar, and Science Direct databases. The search terms were "anticancer", "indole", "cell lines", "structure-activity relationship" and "cytotoxic activity."[a] A.

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Identification of new 3-phenyl-1H-indole-2-carbohydrazide derivatives and their structure–activity relationships as potent tubulin inhibitors and anticancer agents: A combined in silico, in vitro and synthetic study

Cited by 14 publications

References 57 publications

Recent Advances of Tubulin Inhibitors Targeting the Colchicine Binding Site for Cancer Therapy

Recent Advances of Tubulin Inhibitors Targeting the Colchicine Binding Site for Cancer Therapy

Indole derivatives targeting colchicine binding site as potential anticancer agents

Indole Derived Anticancer Agents

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