New pyridazine derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents; design, synthesis and biological evaluation

Ahmed, Eman M.; Hassan, Marwa S.A.; El‐Malah, Afaf; Kassab, Asmaa E.

doi:10.1016/j.bioorg.2019.103497

Cited by 30 publications

(18 citation statements)

References 30 publications

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“…Simultaneously, western blot analysis (Fig. 3C) showed that the levels of invasion-related proteins were inhibited in the SW480 and LoVo cells by LUNAR1 knockdown (P<0.01), including cyclooxygenase 2 (Cox-2), matrix metalloprotein (MMP)-2 and MMP-9, which play pivotal roles in angiogenesis and tumor metastasis (30). Collectively, LUNAR1 knockdown inhibited CRC cell migration and invasion, indicating that LUNAR1 plays an active role in CRC progression.…”

Section: Resultsmentioning

confidence: 87%

lncRNA LUNAR1 accelerates colorectal cancer progression by targeting the miR‑495‑3p/MYCBP axis

Qian

Garg

et al. 2020

Int J Oncol

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Colorectal cancer (CRC) is a tumor type characterized by high patient morbidity and mortality. It has been reported that long non-coding (lncRNA) LUNAR1 (LUNAR1) participates in the regulation of tumor progression, such as diffuse large B-cell lymphoma. However, its role and underlying mechanisms in CRC progression have not been elucidated. The present study was designed to investigate the underlying mechanisms by which LUNAR1 regulates CRC progression. RT-qPCR and Pearson's correlation analysis revealed that LUNAR1 was highly expressed and was negatively associated with the overall survival of CRC patients. Moreover, CCK-8, clone formation, wound-healing migration, Transwell chamber and FACs assay analyses showed that LUNAR1 knockdown inhibited CRC cell proliferation, migration and invasion, while accelerating cell apoptosis. Additionally, LUNAR1 was found to function as a sponge of miR-495-3p, which was predicted by TargetScan and confirmed by luciferase reporter assay. Furthermore, functional studies indicated that miR-495-3p overexpression inhibited CRC cell proliferation, migration and invasion, while accelerating cell apoptosis. In addition, bioinformatics and luciferase reporter assays showed that miR-495-3p was found to negatively target Myc binding protein (MYCBP), and functional research showed that LUNAR1 accelerated CRC progression via the miR-495-3p/MYCBP axis. In conclusion, LUNAR1 accelerates CRC progression via the miR-495-3p/MYCBP axis, indicating that LUNAR1 may serve as a prognostic biomarker for CRC patients.

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Section: Resultsmentioning

confidence: 87%

lncRNA LUNAR1 accelerates colorectal cancer progression by targeting the miR‑495‑3p/MYCBP axis

Qian

Garg

et al. 2020

Int J Oncol

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“…Notably, the in vivo anti-inflammatory activity of compound 59b was comparable to indomethacin and equipotent to celecoxib. Moreover, compound 59b showed better gastric profile compared to both celecoxib and indomethacin 74 .…”

Section: Recent Development In Anti-inflammatory Agentsmentioning

confidence: 97%

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

Bian

Wu³

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Inflammation and disease are closely related. Inflammation can induce various diseases, and diseases can promote inflammatory response, and two possibly induces each other in a bidirectional loop. Inflammation is usually treated using synthetic anti-inflammatory drugs which are associated with several adverse effects hence are not safe for long-term use. Therefore, there is need for anti-inflammatory drugs which are not only effective but also safe. Several researchers have devoted to the research and development of effective anti-inflammatory drugs with little or no side effects. In this review, we studied some small molecules with reported anti-inflammatory activities and hence potential sources of anti-inflammatory agents. The information was retrieved from relevant studies published between January 2019 and May, 2021 for review. This review study was aimed to provide relevant information towards the design and development of effective and safe anti-inflammation agents.

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“…Rats were starved for 18 hr before the experiment and were divided into seven groups of six rats each, and the tested compounds, references (celecoxib and indomethacin), or saline as control were administered orally at a dose of 10 mg/kg body weight. [48] Then, 4 hr after the treatment, the animals were killed and their stomachs were removed and examined macroscopically using a magnifying lens. A longitudinal incision along the greater curvature was made with a fine scissor.…”

Section: Gastric Ulcerogenic Activitymentioning

confidence: 99%

Design, synthesis, and biological evaluation of new pyrazoloquinazoline derivatives as dual COX‐2/5‐LOX inhibitors

Shaaban

Kamal

Faggal

et al. 2020

Archiv der Pharmazie

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A new series of pyrazoloquinazoline derivatives equipped with different chalcones was designed, synthesized, and identified through 1 H nuclear magnetic resonance (NMR), 13 C NMR, and infrared spectroscopic techniques. Our design strategy of the quinazolinone-privileged scaffold as a new scaffold was based on merging pharmacophores previously reported to exhibit cyclooxygenase-2 (COX-2)/5lipoxygenase (5-LOX) inhibitory activity. All the newly synthesized derivatives were biologically evaluated for COX and 5-LOX inhibitory activity and COX-2 selectivity, using celecoxib and zileuton as reference drugs, as they exhibited promising antiinflammatory activity. Compound 3j was found to be the most promising derivative, with IC 50 values of 667 and 47 nM against COX-1 and COX-2, respectively, which are superior to that of celecoxib (IC 50 value against COX-2 = 95 nM), showing an SI of 14.2 that was much better than celecoxib. Compounds 3f and 3h exhibited COX-1 inhibition, with IC 50 values of 1,485 and 684 nM, respectively. The synthesized compounds showed a significant inhibitory activity against 5-LOX, with IC 50 values ranging from 0.6 to 4.3 µM, where compounds 3f and 3h were found to be the most potent derivatives, with IC 50 values of 0.6 and 1.0 µM, respectively, in comparison with that of zileuton (IC 50 = 0.8 µM). These promising derivatives, 3f, 3h, and 3j, were further investigated in vivo for anti-inflammatory, gastric ulcerogenic effects, and prostaglandin production (PGE2) in rat serum. The molecular docking studies concerning the binding sites of COX-2 and 5-LOX revealed similar orientation, compared with reported inhibitors, which encouraged us to design new leads targeting COX-2 and 5-LOX as dual inhibitors, as a new avenue in anti-inflammatory therapy.

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New pyridazine derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents; design, synthesis and biological evaluation

Cited by 30 publications

References 30 publications

lncRNA LUNAR1 accelerates colorectal cancer progression by targeting the miR‑495‑3p/MYCBP axis

lncRNA LUNAR1 accelerates colorectal cancer progression by targeting the miR‑495‑3p/MYCBP axis

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

Design, synthesis, and biological evaluation of new pyrazoloquinazoline derivatives as dual COX‐2/5‐LOX inhibitors

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