Novel indole hydrazide derivatives: Synthesis and their antiproliferative activities through inducing apoptosis and DNA damage

Kılıç-Kurt, Zühal; Acar, Cemre; Ergül, Mustafa; Bakar‐Ates, Filiz; Altuntas, T. Gul

doi:10.1002/ardp.202000059

Cited by 5 publications

(3 citation statements)

References 21 publications

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“…The effective pathway induced cell cycle arrest at the S-phase, and it led to apoptosis in the MCF-7 cells. EGFR, and its downstreaming pathway is considered one of the promising effective pathways for cancer treatment, and our results agreed with previous reported studies for the same compounds' scaffold affecting cytotoxic activities through apoptosis [33][34][35]. for cancer treatment, and our results agreed with previous reported studies for the same compounds' scaffold affecting cytotoxic activities through apoptosis [33][34][35].…”

Section: Molecular Dockingsupporting

confidence: 93%

Discovery of Potent Indolyl-Hydrazones as Kinase Inhibitors for Breast Cancer: Synthesis, X-ray Single-Crystal Analysis, and In Vitro and In Vivo Anti-Cancer Activity Evaluation

Salama,

Youssef,

Aboelmagd

et al. 2023

Pharmaceuticals

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According to data provided by the World Health Organization (WHO), a total of 2.3 million women across the globe received a diagnosis of breast cancer in the year 2020, and among these cases, 685,000 resulted in fatalities. As the incidence of breast cancer statistics continues to rise, it is imperative to explore new avenues in the ongoing battle against this disease. Therefore, a number of new indolyl-hydrazones were synthesized by reacting the ethyl 3-formyl-1H-indole-2-carboxylate 1 with thiosemicarbazide, semicarbazide.HCl, 4-nitrophenyl hydrazine, 2,4-dinitrophenyl hydrazine, and 4-amino-5-(1H-indol-2-yl)-1,2,4-triazole-3-thione to afford the new hit compounds, which were assigned chemical structures as thiosemicarbazone 3, bis(hydrazine derivative) 5, semicarbzone 6, Schiff base 8, and the corresponding hydrazones 10 and 12 by NMR, elemental analysis, and X-ray single-crystal analysis. The MTT assay was employed to investigate the compounds’ cytotoxicity against breast cancer cells (MCF-7). Cytotoxicity results disclosed potent IC50 values against MCF-7, especially compounds 5, 8, and 12, with IC50 values of 2.73 ± 0.14, 4.38 ± 0.23, and 7.03 ± 0.37 μM, respectively, compared to staurosproine (IC50 = 8.32 ± 0.43 μM). Consequently, the activities of compounds 5, 8, and 12 in relation to cell migration were investigated using the wound-healing test. The findings revealed notable wound-healing efficacy, with respective percentages of wound closure measured at 48.8%, 60.7%, and 51.8%. The impact of the hit compounds on cell proliferation was assessed by examining their apoptosis-inducing properties. Intriguingly, compound 5 exhibited a significant enhancement in cell death within MCF-7 cells, registering a notable increase of 39.26% in comparison to the untreated control group, which demonstrated only 1.27% cell death. Furthermore, the mechanism of action of compound 5 was scrutinized through testing against kinase receptors. The results revealed significant kinase inhibition, particularly against PI3K-α, PI3K-β, PI3K-δ, CDK2, AKT-1, and EGFR, showcasing promising activity, compared to standard drugs targeting these receptors. In the conclusive phase, through in vivo assay, compound 5 demonstrated a substantial reduction in tumor volume, decreasing from 106 mm³ in the untreated control to 56.4 mm³. Moreover, it significantly attenuated tumor proliferation by 46.9%. In view of these findings, the identified leads exhibit promises for potential development into future medications for the treatment of breast cancer, as they effectively hinder both cell migration and proliferation.

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Section: Molecular Dockingsupporting

confidence: 93%

Discovery of Potent Indolyl-Hydrazones as Kinase Inhibitors for Breast Cancer: Synthesis, X-ray Single-Crystal Analysis, and In Vitro and In Vivo Anti-Cancer Activity Evaluation

Salama,

Youssef,

Aboelmagd

et al. 2023

Pharmaceuticals

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“…Our results are in contrast with what has been observed for other indole derivatives. Indeed, a series of indole hydrazide (Kilic-Kurt et al,2020)and bisindolinone derivatives (Amato et al, 2014) induced DNA damage in breast adenocarcinoma MCF-7 cells and in human transformed fibroblasts (BJ-EHLT), as shown by a significant increase in H2AX phosphorylation (Kilic-Kurt et al,2020,Amato et al, 2014.…”

Section: 8compound 7c Lacks Genotoxic Activitymentioning

confidence: 99%

Synthesis, in vitro cytotoxicity, molecular docking and ADME study of some indolin-2-one linked 1,2,3-triazole derivatives

Das

Greco

Kumar

et al. 2022

Computational Biology and Chemistry

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“…Hydrazones have been demonstrated to possess antimicrobial, anti-inflammatory and antitumor activities. [31][32][33][34] Hydrazones possessing an azometine -NHN = CH-proton constitute an important class of compounds for drug development. In addition, the pharmacophore ingredient with CO-NH-N = CH (hydrazide-hydrazones) has received considerable attention due to its broad spectrum of biological applications.…”

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confidence: 99%

Synthesis and Cytotoxic Activity of Novel Betulin Derivatives Containing Hydrazide-Hydrazone Moieties

Wang

Han

et al. 2021

Natural Product Communications

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A series of novel betulin derivatives containing hydrazide-hydrazone moieties were synthesized. All compounds were evaluated for their cytotoxicity against four human carcinoma cell lines (HepG2, A549, MCF-7 and HCT-116) and a normal human gastric epithelial cell line (GES-1). Among them, compound 6i was the most potent against HepG2 and MCF-7 cell lines, with IC50 values of 9.27 and 8.87 μM, respectively. The results suggest that the incorporation of a hydrazide-hydrazone side chain at the C-28 position of betulin is beneficial for compounds to display significant cytotoxicity. Compound 6i may be used as a promising skeleton for antitumor agents with improved efficacy.

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Novel indole hydrazide derivatives: Synthesis and their antiproliferative activities through inducing apoptosis and DNA damage

Cited by 5 publications

References 21 publications

Discovery of Potent Indolyl-Hydrazones as Kinase Inhibitors for Breast Cancer: Synthesis, X-ray Single-Crystal Analysis, and In Vitro and In Vivo Anti-Cancer Activity Evaluation

Discovery of Potent Indolyl-Hydrazones as Kinase Inhibitors for Breast Cancer: Synthesis, X-ray Single-Crystal Analysis, and In Vitro and In Vivo Anti-Cancer Activity Evaluation

Synthesis, in vitro cytotoxicity, molecular docking and ADME study of some indolin-2-one linked 1,2,3-triazole derivatives

Synthesis and Cytotoxic Activity of Novel Betulin Derivatives Containing Hydrazide-Hydrazone Moieties

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