Discovery and SAR study of 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide: A potent inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) for the treatment of cancer

Zhu, Qihua; Wang, Xueyan; Hu, Yan; He, Xiaorong; Gong, Guoqing; Xu, Yungen

doi:10.1016/j.bmc.2015.09.026

Cited by 16 publications

(8 citation statements)

References 28 publications

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“…It plays a crucial role in tumorigenesis and other diseases. − Once activated by damaged DNA, quadruplexes, or specific dsDNA, PARP-1 cleaves nicotinamide adenine dinucleotide (NAD + ) and polymerizes the resulting ADP-ribose moiety (50–200 molecules) onto target proteins, ultimately forming a hyperbranched poly(ADP-ribose) polymer (PAR). , The large, negatively charged PAR dramatically changes the charge properties of the acceptor proteins and initiates immediate cellular response to DNA damage . Because PARP-1 activity level was related to tumor grade and the efficacy outcome of inhibitor therapy. − It is of great significance to develop some sensitive and accurate PARP-1 activity detection method for clinical diagnosis and drug screening in the treatment of various cancers. − …”

mentioning

confidence: 99%

Quartz Crystal Microbalance Detection of Poly(ADP-ribose) Polymerase-1 Based on Gold Nanorods Signal Amplification

Yang

Wang

et al. 2019

Anal. Chem.

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Recent findings have thrust poly(ADP-ribose) polymerase-1 (PARP-1) into the limelight as a potential biomarker and chemotherapeutic target for cancer. Thus, a sensitive method for detection of PARP-1 is necessary for early diagnosis of cancer and drug development. However, the poor electrochemical and optical activity of PARP-1 and its product poly(ADP-ribose) (PAR) prompted researchers to develop more methods. Here, we developed an efficient method for the determination of PARP-1 by using quartz crystal microbalance (QCM) because it is mass-sensitive. Once activated by the specific DNA, PARP-1 cleaves nicotinamideadenine dinucleotide (NAD + ) into nicotinamide and ADP-ribose to synthesize a hyperbranched poly(ADP-ribose) polymer. Although QCM is mass-sensitive, it is not sensitive enough to discern PAR effectively. So, positively charged cetyltrimethylammonium bromide (CTAB)-coated gold nanorods (GNRs) were introduced to increase the frequency change significantly because of the strong electrostatic interaction between them with negatively charged PAR. PARP-1 ranging from 0.06 to 3 nM can be facilely detected with a low detection limit of 0.04 nM. The strategy has been used to evaluate PARP-1 inhibitors and to detect PARP-1 activity in real cancer cells lysate with satisfactory results, indicating that it was a promising candidate for clinical diagnosis and drug screening in the future.

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confidence: 99%

Quartz Crystal Microbalance Detection of Poly(ADP-ribose) Polymerase-1 Based on Gold Nanorods Signal Amplification

Yang

Wang

et al. 2019

Anal. Chem.

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“…The obtained compound was also tested in the combination with temozolomide on three human tumor cell lines MDA-MB-468, SW-620 and A549. Research revealed an appreciable increase in the potency of growth inhibition of tumor cells in comparison with the application of only temozolomide [ 30 ].…”

Section: Biological Properties Of Imidazo[45- B mentioning

confidence: 99%

Pharmacological Potential and Synthetic Approaches of Imidazo[4,5-b]pyridine and Imidazo[4,5-c]pyridine Derivatives

2017

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The structural resemblance between the fused imidazopyridine heterocyclic ring system and purines has prompted biological investigations to assess their potential therapeutic significance. They are known to play a crucial role in numerous disease conditions. The discovery of their first bioactivity as GABAA receptor positive allosteric modulators divulged their medicinal potential. Proton pump inhibitors, aromatase inhibitors, and NSAIDs were also found in this chemical group. Imidazopyridines have the ability to influence many cellular pathways necessary for the proper functioning of cancerous cells, pathogens, components of the immune system, enzymes involved in carbohydrate metabolism, etc. The collective results of biochemical and biophysical properties foregrounded their medicinal significance in central nervous system, digestive system, cancer, inflammation, etc. In recent years, new preparative methods for the synthesis of imidazopyridines using various catalysts have been described. The present manuscript to the best of our knowledge is the complete compilation on the synthesis and medicinal aspects of imidazo[4,5-b]pyridines and imidazo[4,5-c]pyridines reported from the year 2000 to date, including structure–activity relationships.

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“…Approximately 90% of the total PARylation in a living cell is assumed by poly(ADP-ribose) polymerase-1 (PARP), which plays important roles not only in DNA repair, − transcriptional control, and DNA damage-induced cell death but also in the restriction of aging rate . Recent research demonstrates that the inhibitors of PARP are effective adjuvant therapeutics for various cancers. − Thus, the studies on PARylation, especially the fabrication of biosensors for PARP and its inhibitors, are of great importance.…”

Section: Introductionmentioning

confidence: 99%

Stable and Reusable Electrochemical Biosensor for Poly(ADP-ribose) Polymerase and Its Inhibitor Based on Enzyme-Initiated Auto-PARylation

Liu

Wang

et al. 2016

ACS Appl. Mater. Interfaces

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A stable and reusable electrochemical biosensor for the label-free detection of poly(ADP-ribose) polymerase (PARP) is designed in this work. C-kit-1, a thiol-modified G-quadruplex oligonucleotide, is first self-assembled on a gold electrode surface. The G-quadruplex structure of c-kit-1 can specifically tether and activate PARP, resulting in the generation of negatively charged poly(ADP-ribose) polymer (PAR). On the basis of electrostatic attraction, PAR facilitates the surface accumulation of positively charged electrochemical signal molecules. Through the characterization of electrochemical signal molecules, the label-free quantification of PARP is simply implemented. On the basis of the proposed method, selective quantification of PARP can be achieved over the linear range from 0.01 to 1 U with a calculated detection limit of 0.003U. Further studies also demonstrate the applicability of the proposed method to biosamples revealing the broad potential in practical applications. Furthermore, inhibitor of PARP has also been detected with this biosensor. Meanwhile, benefited from self-assembly on solid surface, this biosensor possesses two important features, i.e., reusability and stability, which are desirable in related biosensors.

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Discovery and SAR study of 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide: A potent inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) for the treatment of cancer

Cited by 16 publications

References 28 publications

Quartz Crystal Microbalance Detection of Poly(ADP-ribose) Polymerase-1 Based on Gold Nanorods Signal Amplification

Quartz Crystal Microbalance Detection of Poly(ADP-ribose) Polymerase-1 Based on Gold Nanorods Signal Amplification

Pharmacological Potential and Synthetic Approaches of Imidazo[4,5-b]pyridine and Imidazo[4,5-c]pyridine Derivatives

Stable and Reusable Electrochemical Biosensor for Poly(ADP-ribose) Polymerase and Its Inhibitor Based on Enzyme-Initiated Auto-PARylation

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