Triad pyrazole–thiazole–coumarin heterocyclic core effectively inhibit HSP and drive cancer cells to apoptosis

Gümüş, Mehmet; Koca, İrfan; Sert, Yusuf; Dişli, Ali; Tunoglu, Ezgi Nurdan Yenilmez; Tutar, Lütfi; Tutar, Yusuf

doi:10.1080/07391102.2023.2181643

Cited by 10 publications

(6 citation statements)

References 49 publications

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“…After pretreatment with different concentrations of the compounds for 48 h, 10 µl of 5 mg/mL MTT solution was added to each well and incubated for 4 h at 37 ○ C, and 100 µl of DMSO was used in each well to dissolve the blue formazan crystals. Then, the absorbance was measured at 570 nm [ 61 ]. The cell viability percentages of compound 4o against MCF-7 cancer cell lines and L929 normal cell lines were presented in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…MCF-7 cancer cell lines were cultured at Dulbecco’s Modified Eagle Medium High Glucose (DMEM) (EuroClone, Via Figino, Italy); fetal bovine serum (FBS) and MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyl Tetrazolium Bromide) were provided by Sigma-Aldrich (Darmstadt, Germany); ApopNexin Annexin-V-FITC with PI Apoptosis Kit was obtained from Merck (Darmstadt, Germany); Total RNA Isolation Kit was provided by Analytic Jena (Jena, Germany), SensiFast cDNA Synthesis Kit was provided by Meridian Bioscience (Cincinati, USA), SybrGreen Master Mix was obtained from EuroClone (Via Figino, Italy) [ 61 , 62 ].…”

Section: Methodsmentioning

confidence: 99%

“…RNA extracted from MCF-7 cells treated with 4o converted to cDNA. The expression level of the cell line was compared to non-treated cells to evaluate the effect of the compound with previously established methods [ 61 , 62 ]. The results were analyzed using gene enrichment analysis (Reactome and EnrichR pathways).…”

Section: Methodsmentioning

confidence: 99%

“…In the absence of 4o, the expression level of each gene is taken as a unity by using b-actin housekeeping gene expression. Gene expression in the presence of the compound was taken relative to unity (See supplementary file for primers and fold expression change) [ 61 – 63 ].…”

Section: Methodsmentioning

confidence: 99%

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Synthesis of novel carbazole hydrazine-carbothioamide scaffold as potent antioxidant, anticancer and antimicrobial agents

Çapan,

Hawash,

Qaoud

et al. 2024

BMC Chemistry

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Background Carbazole-based molecules containing thiosemicarbazide functional groups are recognized for their diverse biological activities, particularly in enhancing therapeutic anticancer effects through inhibiting crucial pathways. These derivatives also exhibit noteworthy antioxidant properties. Objectives This study aims to synthesize, characterize, and evaluate the antioxidant and anticancer activities of 18 novel carbazole derivatives. Methods The radical scavenging capabilities of the compounds were assessed using the 2,2-diphenyl-1-picrylhydrazyl assay. Antiproliferative activities were evaluated on MCF-7 cancer cell lines through viability assays. Additionally, the modulation of the PI3K/Akt/mTOR pathway, apoptosis/necrosis induction, and cell cycle analysis were conducted for the most promising anticancer agents. Results nine compounds showed potent antioxidant activities with IC50 values lower than the positive control acarbose, with compounds 4 h and 4y exhibiting the highest potency (IC50 values of 0.73 and 0.38 µM, respectively). Furthermore, compounds 4o and 4r displayed significant anticancer effects, with IC50 values of 2.02 and 4.99 µM, respectively. Compound 4o, in particular, exhibited promising activity by targeting the PI3K/Akt/mTOR signaling pathway, inhibiting tumor survival, inducing apoptosis, and causing cell cycle arrest in MCF-7 cell lines. Furthermore, compound 4o was showed significant antimicrobial activities against S. aureus and E. coli, and antifungal effect against C. albicans. Its potential to overcome drug resistance through this pathway inhibition highlights its promise as an anticancer agent. Molecular docking simulations supported these findings, revealing favorable binding profiles and interactions within the active sites of the enzymes PI3K, AKT1, and mTOR. Moreover, assessing the druggability of the newly synthesized thiosemicarbazide derivatives demonstrated optimal physicochemical properties, further endorsing their potential as drug candidates.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis of novel carbazole hydrazine-carbothioamide scaffold as potent antioxidant, anticancer and antimicrobial agents

Çapan,

Hawash,

Qaoud

et al. 2024

BMC Chemistry

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“…Heat shock proteins (HSPs) are intracellular proteins whose expression increases in response to stresses such as heat [33]. In the context of cancer, HSPs play critical roles in cell survival, proliferation, and therapeutic resistance [34,35]. They also help in maintaining intracellular homeostasis by preventing the accumulation of harmful ROS [36].…”

Section: Introductionmentioning

confidence: 99%

Inhibiting AGS Cancer Cell Proliferation through the Combined Application of Aucklandiae Radix and Hyperthermia: Investigating the Roles of Heat Shock Proteins and Reactive Oxygen Species

Ahn,

Ha,

Kim

et al. 2024

Antioxidants

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Cancer is a major global health concern. To address this, the combination of traditional medicine and newly appreciated therapeutic modalities has been gaining considerable attention. This study explores the combined effects of Aucklandiae Radix (AR) and 43 °C hyperthermia (HT) on human gastric adenocarcinoma (AGS) cell proliferation and apoptosis. We investigated the synergistic effects of AR and HT on cell viability, apoptosis, cell cycle progression, and reactive oxygen species (ROS)-dependent mechanisms. Our findings suggest that the combined treatment led to a notable decrease in AGS cell viability and increased apoptosis. Furthermore, cell cycle arrest at the G2/M phase contributed to the inhibition of cancer cell proliferation. Notably, the roles of heat shock proteins (HSPs) were highlighted, particularly in the context of ROS regulation and the induction of apoptosis. Overexpression of HSPs was observed in cells subjected to HT, whereas their levels were markedly reduced following AR treatment. The suppression of HSPs and the subsequent increase in ROS levels appeared to contribute to the activation of apoptosis, suggesting a potential role for HSPs in the combined therapy’s anti-cancer mechanisms. These findings provide valuable insights into the potential of integrating AR and HT in cancer and HSPs.

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Insight into the therapeutic potential of pyrazole‐thiazole hybrids: A comprehensive review

Sumran,

Sharma,

Aggarwal

2024

Archiv der Pharmazie

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Several pyrazole‐thiazole hybrids featuring two potentially bioactive pharmacophores with or without linker have been synthesized using the molecular hybridization approach as target structures by medicinal chemists to modulate multiple drug targets simultaneously. The presented review aims to provide an overview of the diversified and wide array of pharmacological activities of these hybrids bestowing anticancer, antifungal, antibacterial, analgesic, anti‐inflammatory, antioxidant, antitubercular, antiviral, antiparasitic, and miscellaneous activities. The structure–activity relationships and potential mechanism of action are also reviewed to shed light on the development of more effective and biotargeted candidates. This review focuses on the latest research advances in the biological profile of pyrazole‐thiazole hybrids reported from 2015 to the present, providing medicinal researchers with a comprehensive platform to rationally design and develop more promising pyrazole‐thiazole hybrids.

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Triad pyrazole–thiazole–coumarin heterocyclic core effectively inhibit HSP and drive cancer cells to apoptosis

Cited by 10 publications

References 49 publications

Synthesis of novel carbazole hydrazine-carbothioamide scaffold as potent antioxidant, anticancer and antimicrobial agents

Synthesis of novel carbazole hydrazine-carbothioamide scaffold as potent antioxidant, anticancer and antimicrobial agents

Inhibiting AGS Cancer Cell Proliferation through the Combined Application of Aucklandiae Radix and Hyperthermia: Investigating the Roles of Heat Shock Proteins and Reactive Oxygen Species

Insight into the therapeutic potential of pyrazole‐thiazole hybrids: A comprehensive review

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