A Novel Imidazo[1,2-a]pyridine Compound Reduces Cell Viability and Induces Apoptosis of HeLa Cells by p53/Bax-Mediated Activation of Mitochondrial Pathway.

Abstract

BACKGROUND:

Despite emerging research on new treatment strategies, chemotherapy remains one of the most important therapeutic modalities for cancers. Imidazopyridines are important targets in organic chemistry and, given their numerous applications, they are worthy of attention.

OBJECTIVE:

The objective of this study was to design and synthesize a novel series of imidazo[1,2-a]pyridine-derived compounds and investigate their antitumor effects and the underlying mechanisms.

METHODS:

Imidazo[1,2-a]pyridine-derived compounds were synthesized with new strategies and conventional methods. The antitumor activities of the new compounds were evaluated by MTT assay. Flow cytometry and immunofluorescence were performed to examine the effects of the most effective antiproliferative compound on cell apoptosis. Western blot analysis was used to assess the expression of apoptotic proteins.

RESULTS:

Fifty-two new imidazo[1,2-a]pyridine compounds were designed and successfully synthesized. The compound, 1-(imidazo[1,2-a]pyridin-3-yl)-2-(naphthalen-2-yl)ethane-1,2-dione, named La23, showed high potential for suppressing the viability of HeLa cells (IC50 15.32 μM). La23 inhibited cell proliferation by inducing cell apoptosis, and it reduced the mitochondrial membrane potential of HeLa cells. Moreover, treatment with La23 appeared to increase the expression of apoptotic-related protein P53, Bax, cleaved caspase-3, and cytochrome c at a low concentration range.

CONCLUSION:

The novel imidazo[1,2-a]pyridine compound, La23, was synthesized and it suppressed cell growth by inducing cell apoptosis via the p53/Bax mitochondrial apoptotic pathway.

• Authors: Yang Yu, Yanwen Li, Xinjie Yang, Qiuyi Deng, Bin Xu, Hua Cao, Jianwen Mao
• Journal: Anti-cancer agents in medicinal chemistry (Anticancer Agents Med Chem) Vol. 22 Issue 6 Pg. 1102-1110 ( 2022) ISSN: 1875-5992 [Electronic] Netherlands
• PMID: 34353269 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Antineoplastic Agents
• Pyridines
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• pyridine

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis
• Cell Proliferation
• Cell Survival
• HeLa Cells
• Humans
• Membrane Potential, Mitochondrial
• Pyridines
• Tumor Suppressor Protein p53 (metabolism)
• bcl-2-Associated X Protein (metabolism)