Biphasic Dose‐Dependent G0/G1 and G2/M Cell‐Cycle Arrest by Synthetic 2,3‐Arylpyridylindole Derivatives in A549 Lung Cancer Cells

Chaiputtanapun, Pongtai; Lirdprapamongkol, Kriengsak; Thanaussavadate, Bongkotrat; Phongphankhum, Thanyaporn; Thippong, Thanawit; Thangsan, Poomsith; Montatip, Phreeranat; Ngiwsara, Lukana; Svasti, Jisnuson; Chuawong, Pitak

doi:10.1002/cmdc.202200127

Cited by 8 publications

(7 citation statements)

References 47 publications

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“…Notably, p53 plays such a key role in cell cycle controlling (Cappadone et al, 2015;Ho et al, 2021;Hu et al, 2021), that might directly influence different steps of the cell cycle. On the other hand, compounds induce the steps of cell cycle arrest in a dose-dependent manner (Chaiputtanapun et al, 2022). The different concentration of CI in both cell lines may also contribute to its effects on cycle arrest.…”

Section: Discussionmentioning

confidence: 99%

Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway

et al. 2023

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Cinobufacini injection (CI), an aqueous extract of Cutis Bufonis, is clinically used for cancer therapy in China, but its molecular mechanism for the treatment of osteosarcoma (OS) remains unclear. We constructed U2OS ectopic subcutaneous tumor model to verify the anti-OS effect of CI in vivo. Meanwhile, cell proliferation of U2OS and MG63 cells was monitored in vitro using the CCK-8 assay, colony formation and morphological changes. Cell cycle arrest and apoptosis were detected by flow cytometry and western blot, which showed that CI significantly inhibited proliferation, induced cell cycle arrest and apoptosis in human OS cells. The further RNA-seq results identified that the Hippo signaling pathway was involved in the anti-OS effect of CI. YAP/TAZ are two major components of the Hippo pathway in breast cancer and are positively regulated by prolyl isomerase PIN1, we assessed their role in OS using both clinicopathological sections and western blots. CI also inhibited PIN1 enzyme activity in a dose-dependent manner, which resulted in impaired PIN1, YAP, and TAZ expression in vitro and in vivo. Additionally, 15 potential compounds of CI were found to occupy the PIN1 kinase domain and inhibit its activity. In summary, CI plays an anti-OS role by down-regulating the PIN1-YAP/TAZ pathway.

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Section: Discussionmentioning

confidence: 99%

Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway

et al. 2023

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“…Based on the binding site, the synthesis of small molecules must be carried out for the MDM2-p53 interaction inhibition and a better understanding of the molecular mechanism of p53 activation. [96][97][98][99]…”

Section: Future Perspectivesmentioning

confidence: 99%

Insight on Heterocycles as p53‐MDM2 Protein‐Protein Interaction Inhibitors: Molecular Mechanism for p53 Activation

Basha,

Mohan

2024

ChemistrySelect

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Transcription factor p53, also known as tumor suppressor protein. Encoded by the TP53 gene, the guardian of genome p53 regulates many gene pathways. Nevertheless, the molecular mechanisms of p53 functioning have been known for a few decades, and the exact role of p53 in cancer therapy is unclear. Also, comprehensive literature on heterocycles as p53‐MDM2 protein‐protein interaction inhibitors is limited. This review covers the molecular mechanism for the p53‐MDM2 interaction and its inhibition by the heterocyclic small molecules. We hope the present comprehensive study will help to develop heterocycles as anticancer drugs that induce apoptosis in tumor cells.

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“…The same group recently developed 2,3‐arylpyridylindole derivatives and investigated for their in vitro cytotoxic activity against A549 human lung cancer cells. The methyl 4‐(2‐(pyridin‐3‐yl)‐1 H ‐indol‐3‐yl)benzoate and methyl 4‐(2‐(pyridin‐4‐yl)‐1 H ‐indol‐3‐yl)benzoate ( 41 ) expressed good cytotoxicity with IC 50 values of 1.18 and 0.87 μM respectively and inhibited tubulin polymerization in vitro , with molecular docking studies suggesting the binding modes of the compounds in the Colchicine binding site [82] . The structures of indole derivatives ( 37 – 41 ) displayed anticancer activities are shown in Figure 8.…”

Section: Bioactivity Evaluationmentioning

confidence: 99%

The Multi‐Pharmacological Targeted Role of Indole and its Derivatives: A review

Mathada¹,

Yernale

Basha³

2023

ChemistrySelect

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Heterocycles are a privileged motif that appears as a momentous objective in medicinal chemistry. An important class of compounds for drug discovery and design is indole and its derivatives, which have been examined for a variety of biological activities. Therefore, it is noteworthy in the modern progress of synthetic, medicinal chemistry; the last decade has been onlooker with a multitude of reports on several indole derivatives corroborating these chemical entities to be a renowned target for the discovery of new drugs. The current study includes brief natural sources of indole, and a new range of commercially available indole‐based drugs. Additionally, this review discusses the numerous facets of the structure‐activity relationship study (SARs) and provides information about the varied pharmacological effects of indole derivatives. The literature data presented for the anti‐pharmacological agents herein covers largely from the year 2015 to mid of 2022.

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Biphasic Dose‐Dependent G0/G1 and G2/M Cell‐Cycle Arrest by Synthetic 2,3‐Arylpyridylindole Derivatives in A549 Lung Cancer Cells

Cited by 8 publications

References 47 publications

Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway

Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway

Insight on Heterocycles as p53‐MDM2 Protein‐Protein Interaction Inhibitors: Molecular Mechanism for p53 Activation

The Multi‐Pharmacological Targeted Role of Indole and its Derivatives: A review

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