Novel imidazo[1,2-a]pyridine derivatives induce apoptosis and cell cycle arrest in non-small cell lung cancer by activating NADPH oxidase mediated oxidative stress

Bhavya, Kumari; Mantipally, Manohar; Roy, Soumyajit; Arora, Leena; Badavath, Vishnu Nayak; Gangireddy, Madhusudhanareddy; Dasgupta, Suman; Gundla, Rambabu; Pal, Durba

doi:10.1016/j.lfs.2022.120334

Cited by 9 publications

(4 citation statements)

References 58 publications

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“… 74 Also, Bhavya et al have shown that novel imidazo [1,2- a ] pyridine derivatives enhance pro-apoptotic BAX expression, and reduce Bcl-2 expression in A549 cells. 75 In this investigation, the impacts of MIA on the BAX and Bcl-2 protein expression was assessed in IL-6-induced breast and ovarian cancer cells. The western blot results revealed that MIA suppressed Bcl-2 expression while boosting BAX protein expression.…”

Section: Discussionmentioning

confidence: 99%

A novel imidazo[1,2-a]pyridine derivative and its co-administration with curcumin exert anti-inflammatory effects by modulating the STAT3/NF-κB/iNOS/COX-2 signaling pathway in breast and ovarian cancer cell lines

Noori¹,

Daraei²,

Movahed³

et al. 2023

Bioimpacts

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Imidazo[1,2-a]pyridine derivatives with diverse pharmacological properties and Curcumin, as a potential natural anti-inflammatory compound, are promising compounds for cancer treatment. This study aimed to synthesize a novel imidazo[1,2-a]pyridine derivative, (MIA), and evaluate its anti-inflammatory activity and effects on nuclear factor-kB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways, and their target genes, alone and in combination with curcumin, in MDA-MB-231 and SKOV3 cell lines. Methods: We evaluated the interaction between imidazo[1,2-a]pyridine ligand, curcumin, and NF-κB p50 protein using the molecular docking studies. MTT assay was used to investigate the impacts of compounds on cell viability. To evaluate the NF-κB DNA binding activity and the level of inflammatory cytokines in response to the compounds, ELISA-based methods were performed. In addition, quantitative polymerase chain reaction (qPCR) and western blotting were carried out to analyze the expression of genes and investigate NF-κB and STAT3 signaling pathways. Results: Molecular docking studies showed that MIA docked into the NF-κB p50 subunit, and curcumin augmented its binding. The MTT assay results indicated that MIA and its combination with curcumin reduced cell viability. According to the results of the ELISA-based methods, MIA lowered the levels of inflammatory cytokines and suppressed NF-κB activity. In addition, real-time PCR and Griess test results showed that the expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) genes, and nitrite production were reduced by MIA. Furthermore, the western blotting analysis demonstrated that MIA increased the expression of inhibitory κB (IκBα) and B-cell lymphoma 2 (Bcl-2)-associated X proteins (BAX), and suppressed the STAT3 phosphorylation, and Bcl-2 expression. Our findings revealed that curcumin had a potentiating role and enhanced all the anti-inflammatory effects of MIA. Conclusion: This study indicated that the anti-inflammatory activity of MIA is exerted by suppressing the NF-κB and STAT3 signaling pathways in MDA-MB-231 and SKOV3 cancer cell lines.

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Section: Discussionmentioning

confidence: 99%

A novel imidazo[1,2-a]pyridine derivative and its co-administration with curcumin exert anti-inflammatory effects by modulating the STAT3/NF-κB/iNOS/COX-2 signaling pathway in breast and ovarian cancer cell lines

Noori¹,

Daraei²,

Movahed³

et al. 2023

Bioimpacts

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“…Lung cancer, the most common form of cancer, is the leading cause of cancer-related death [1]. Among them, NSCLC is the most common type of lung cancer, accounting for about 85% of the total [2].…”

Section: Introductionmentioning

confidence: 99%

METTL3-mediated m6A modification enhances ZDHHC16 expression in nonsmall- cell lung cancer patients, attenuating ferroptosis by suppressing CREB ubiquitination

Zeyu Liu,

Chuanqing Jing,

Wei Zhang

2024

Cell Mol Biol (Noisy-le-grand)

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At present, the early diagnosis and treatment of non-small cell lung cancer (NSCLC) is still an urgent problem to be solved worldwide, including in China. The present work investigated the possible protective effect of ZDHHC16 in cell proliferation and metastasis of NSCLC and explored its possible mechanisms. ZDHHC16 expression level in patients with Non-Small-Cell Lung Cancer was up-regulation. ZDHHC16 gene is stabilized by m6A methylation. ZDHHC16 gene reduced ferroptosis of NSCLC by the rehabilitation of the mitochondrial structure. ZDHHC16 promoted CREB expression through the inhibition of CREB Ubiquitination. Confocal microscopy showed that ZDHHC16 reduced the CREB expression of NSCLC. ZDHHC16 up-regulation reduced CREB Ubiquitination, and down-regulation of ZDHHC16 promoted CREB Ubiquitination of NSCLC. CREB Agonists reduced the effects of ZDHHC16 on ferroptosis, not affecting the Warburg effect of NSCLC. CREB inhibitor reduced the effects of si-ZDHHC16 on ferroptosis, not affecting the Warburg effect of NSCLC. METTL3-mediated m6A modification increases ZDHHC16 stability. Our study revealed that the m6A-forming enzyme METTL3 upregulates ZDHHC16 expression in NSCLC patients, leading to the reduction of ferroptosis by inhibiting CREB ubiquitination.

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“…Molecular hybridization of two or more heterocyclic rings enhances biological activity, such as antimalarial, tubulin inhibition, antibacterial, antidiabetic and anticancer activities [22][23][24][25][26][27]. Several studies have reported that thiazole-pyridine hybrids exhibit cytotoxicity towards cancer cells and can induce apoptosis in cancer cells (Figure 1) [28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, In Vitro Evaluation and Molecular Docking Studies of Novel Thiophenyl Thiazolyl-Pyridine Hybrids as Potential Anticancer Agents

Ashmawy,

Gomha,

Abdallah

et al. 2023

Molecules

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Many literature reports revealed the anticancer activity of pyridine and thiazole derivatives, especially in lung cancer. Therefore, a new series of thiazolyl pyridines linked with thiophene moiety via hydrazone group was prepared by one-pot multi-component reaction of (E)-1-(4-methyl-2-(2-(1-(thiophen-2-yl)ethylidene)hydrazinyl)thiazol-5-yl)ethanone with benzaldehyde derivatives and malononitrile in a good yield. Then, the thiazolyl pyridines were investigated for their in vitro anticancer activity against lung cancer (A549) cell line using MTT assay compared to doxorubicin as a reference drug. The structure of all the newly synthesized compounds was established based on spectroscopic data and elemental analyses. For better insight to investigate their mechanism of action on A549 cell line, docking studies were performed, targeting epidermal growth factor receptor (EGFR) tyrosine kinase. The results obtained revealed that the tested compounds displayed excellent anticancer activities against lung cancer cell line except 8c and 8f compared to reference drug. Based on the data obtained, it can be inferred that the novel compounds, as well as their key intermediate, compound 5, demonstrated potent anticancer activity against lung carcinoma by inhibiting EGFR.

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Novel imidazo[1,2-a]pyridine derivatives induce apoptosis and cell cycle arrest in non-small cell lung cancer by activating NADPH oxidase mediated oxidative stress

Cited by 9 publications

References 58 publications

A novel imidazo[1,2-a]pyridine derivative and its co-administration with curcumin exert anti-inflammatory effects by modulating the STAT3/NF-κB/iNOS/COX-2 signaling pathway in breast and ovarian cancer cell lines

A novel imidazo[1,2-a]pyridine derivative and its co-administration with curcumin exert anti-inflammatory effects by modulating the STAT3/NF-κB/iNOS/COX-2 signaling pathway in breast and ovarian cancer cell lines

METTL3-mediated m6A modification enhances ZDHHC16 expression in nonsmall- cell lung cancer patients, attenuating ferroptosis by suppressing CREB ubiquitination

Synthesis, In Vitro Evaluation and Molecular Docking Studies of Novel Thiophenyl Thiazolyl-Pyridine Hybrids as Potential Anticancer Agents

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