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 are worthy of attention given their numerous applications. Objective: 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 suppressed cell growth by inducing cell apoptosis via the p53/Bax mitochondrial apoptotic pathway.

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

“… 73 Previous study indicated that a new imidazo[1,2- a ]pyridine compound induced apoptosis via the p53/Bax pathway in HeLa cells. 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.…”

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

“…Imidazo[1,2- a ]pyridine is a privileged structure that plays an important role in organic synthesis and in the pharmaceutical industry. This scaffold is present in drugs with several biological activities, such as antiviral [ 1 ], anticonvulsant [ 2 ], antibacterial [ 3 ], antipyretic [ 4 ], antituberculosis [ 5 ], anticancer [ 6 ], anthelmintic [ 5 ], antifungal [ 7 ], analgesic [ 8 ], antiulcer [ 9 ], antiprotozoal [ 10 ], antitumor [ 11 ], and anti-inflammatory [ 12 ]. Examples of commercial drugs are depicted in Figure 1 [ 13 ] and include alpidem (anxiety disorders), minodronic acid (osteoporosis), miroprofen (non-steroidal anti-inflammatory drug, NSAID), necopidem (insomnia), olprinone (acute heart failure), saripidem (type A GABA receptor agonist), zolimidine (gastroesophageal reflux disease), and zolpidem (insomnia).…”