Recent Advances in Anti-inflammatory Potential of Pyridazinone Derivatives

Saini, Minaxi; Mehta, Dinesh Kumar; Das, Rina; Saini, Gurnam

doi:10.2174/1389557516666160611015815

Cited by 16 publications

(25 citation statements)

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“…The pyridazinone nucleuses which are serve as therapeutic agents as nonsteroidal antiinflammatory drugs. This nucleus has a wide spectrum in bioorganic and medicinal chemistry and application in drug discovery (Saini at al., 2016). The aryl-pyridazinonesubstituted benzenesulphonylurea derivatives were tested for their anti-hyperglycaemic activity in glucose-fed hyperglycaemic normal rats.…”

Section: Biological Activitiesmentioning

confidence: 99%

Diverse chemical and biological potentials of various pyridazine and pyridazinone derivatives

Int¹

2019

Preprint

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A series of heterocyclic compounds incorporating pyridazine moiety were for diverse biological activities. Pyridazines and pyridazinones derivatives showed wide spectrum of biological activities such as vasodialator, cardiotonic, anticonvulsant, antihypertensive, antimicrobial, anti-inflammatory, analgesic, anti-feedant, herbicidal, and various other biological, agrochemical and industrial chemical activities. The results illustrated that the synthesized pyridazine/pyridazine compounds have diverse and significant biological activities. Mechanistic insights into the biological properties of pyridazinone derivatives and various synthetic techniques used for their synthesis are also described.

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Section: Biological Activitiesmentioning

confidence: 99%

Diverse chemical and biological potentials of various pyridazine and pyridazinone derivatives

Int¹

2019

Preprint

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“…The pyridazinone structure serves as a potential scaffold for the development of novel anti-inflammatory drugs [11,12]. For example, some pyridazinone derivatives have been reported to inhibit cyclooxygenase 2 (COX2) [13,14]; thus, they belong to the group of nonsteroidal anti-inflammatory drugs (NSAID).…”

Section: Introductionmentioning

confidence: 99%

Pyridazinones and Structurally Related Derivatives with Anti-Inflammatory Activity

et al. 2022

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Persistent inflammation contributes to a number of diseases; therefore, control of the inflammatory response is an important therapeutic goal. In an effort to identify novel anti-inflammatory compounds, we screened a library of pyridazinones and structurally related derivatives that were used previously to identify N-formyl peptide receptor (FPR) agonists. Screening of the compounds for their ability to inhibit lipopolysaccharide (LPS)-induced nuclear factor κB (NF-κB) transcriptional activity in human THP1-Blue monocytic cells identified 48 compounds with anti-inflammatory activity. Interestingly, 34 compounds were FPR agonists, whereas 14 inhibitors of LPS-induced NF-κB activity were not FPR agonists, indicating that they inhibited different signaling pathways. Further analysis of the most potent inhibitors showed that they also inhibited LPS-induced production of interleukin 6 (IL-6) by human MonoMac-6 monocytic cells, again verifying their anti-inflammatory properties. Structure–activity relationship (SAR) classification models based on atom pair descriptors and physicochemical ADME parameters were developed to achieve better insight into the relationships between chemical structures of the compounds and their biological activities, and we found that there was little correlation between FPR agonist activity and inhibition of LPS-induced NF-κB activity. Indeed, Cmpd43, a well-known pyrazolone-based FPR agonist, as well as FPR1 and FPR2 peptide agonists had no effect on the LPS-induced NF-κB activity in THP1-Blue cells. Thus, some FPR agonists reported to have anti-inflammatory activity may actually mediate their effects through FPR-independent pathways, as it is suggested by our results with this series of compounds. This could explain how treatment with some agonists known to be inflammatory (i.e., FPR1 agonists) could result in anti-inflammatory effects. Further research is clearly needed to define the molecular targets of pyridazinones and structurally related compounds with anti-inflammatory activity and to define their relationships (if any) to FPR signaling events.

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“…Recently, pyridazinone derivatives have received substantial attention due to their extensive biological activities. For example, they have been described as anti-inflammatory (Mogilski et al 2015; Saini et al 2016), analgesic (Mogilski et al 2015), anti-viral (Wang et al 2015), anti-parasitic (Jacomini et al 2016), anti-microbial (Faidallah et al 2013), antidiabetic (Rathish et al 2009), anti-cancer (Jin et al 2015; Zhou et al 2014), anti-tubercular (Li et al 2014), as protein kinase inhibitors (Dorsch et al 2015; Elagawany et al 2013; Liu et al 2016), and have also been shown to affect the cardiovascular system (Asif 2015; Costas et al 2015), among others.…”

Section: Introductionmentioning

confidence: 99%

A new pyridazinone exhibits potent cytotoxicity on human cancer cells via apoptosis and poly-ubiquitinated protein accumulation

et al. 2019

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In the last 15 years, pyridazinone derivatives have acquired extensive attention due to their widespread biological activities and pharmacological applications. Pyridazinones are well known for their antimicrobial, anti-viral, anti-inflammatory, anti-cancer, and cardiovascular activities, among others. In this study, we evaluated the anti-cancer activity of a new pyridazinone derivative and propose it as a potential anti-neoplastic agent in acute promyelocytic leukemia cells. Pyr-1 cytotoxicity was assessed on several human cancer and two non-cancerous cell lines by the DNS assay. Pyr-1 demonstrated potent cytotoxicity against 22 human cancer cell lines, exhibiting the most favorable selective cytotoxicity on leukemia (CEM and HL-60), breast (MDA-MB-231 and MDA-MB-468), and lung (A-549) cancer cell lines, when compared with non-cancerous breast epithelial MCF-10A cells. Analyses of apoptosis/necrosis pathways, reactive oxygen species (ROS) production, mitochondria health, caspase-3 activation, and cell cycle profile were performed via flow cytometry. Both hmox-1 RNA and protein expression levels were evaluated by quantitative real-time PCR and Western blotting assays, respectively. Pyr-1 induced apoptosis in acute promyelocytic leukemia cells as confirmed by phosphatidylserine externalization, mitochondrial depolarization, caspase-3 activation, DNA fragmentation, and disrupted cell cycle progression. Additionally, it was determined that Pyr-1 generates oxidative and proteotoxic stress by provoking the accumulation of ROS, resulting in the overexpression of the stress-related hmox-1 mRNA transcripts and protein and a marked increase in poly-ubiquitinated proteins. Our data demonstrate that Pyr-1 induces cell death via the intrinsic apoptosis pathway by accumulating ROS and by impairing proteasome activity.

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Recent Advances in Anti-inflammatory Potential of Pyridazinone Derivatives

Cited by 16 publications

References 0 publications

Diverse chemical and biological potentials of various pyridazine and pyridazinone derivatives

Diverse chemical and biological potentials of various pyridazine and pyridazinone derivatives

Pyridazinones and Structurally Related Derivatives with Anti-Inflammatory Activity

A new pyridazinone exhibits potent cytotoxicity on human cancer cells via apoptosis and poly-ubiquitinated protein accumulation

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