Design, synthesis and biological evaluation of novel indanone containing spiroisoxazoline derivatives with selective COX-2 inhibition as anticancer agents

Abolhasani, Hoda; Zarghi, Afshin; Movahhed, Tahereh Komeili; Abolhasani, Ahmad; Daraei, Bahram; Dastmalchi, Siavoush

doi:10.1016/j.bmc.2020.115960

Cited by 18 publications

(9 citation statements)

References 36 publications

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“…Despite the presence of several NSAIDs, the development of new NSAIDs is attractive, owing to the diverse inflammatory conditions and the need for optimized application in relation to disease and patient conditions. The recent development of NSAIDs comprises modified methyl sulphonyl [ 17 ]; pyrimidine-5-carbonitrile hybrids [ 18 ], pyrazole derivatives [ 19 ], indanone containing spiroisoxazoline derivatives [ 20 ], triazole, and oxadiazole compounds [ 21 , 22 ]. Despite the growing repository of newly synthesized NSAIDs, the development of new compounds is strictly required due to the side effects of the currently approved NSAIDs.…”

Section: Discussionmentioning

confidence: 99%

Drug Discovery of New Anti-Inflammatory Compounds by Targeting Cyclooxygenases

2022

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The goal of achieving anti-inflammatory efficacy with the fewest possible adverse effects through selective COX-2 inhibition is still being investigated in order to develop drugs with safe profiles. This work shows the efficacy and safety profile of two novel benzimidazole piperidine and phenoxy pyridine derivatives in reaching this goal, which would be considered a major achievement in inflammatory therapy. The compounds were evaluated by virtual screening campaign, in vitro cyclooxygenase 1 and 2 (COX-1 and COX-2) inhibition, in vivo carrageenan-induced rat paw edema assay, cytotoxicity against Raw264.7 cells, and histopathological examination of rat paw and stomach. Two new compounds, compound 1 ([(2-{[3-(4-methyl-1H-benzimidazol-2-yl)piperidin-1-yl]carbonyl}phenyl)amino]acetic acid) and compound 2 (ethyl 1-(5-cyano-2-hydroxyphenyl)-4-oxo-5-phenoxy-1,4-dihydropyridine-3-carboxylate) showed high selectivity against COX-2, favourable drug-likeness and ADME descriptors, a lack of cytotoxicity, relived paw edema, and inflammation without noticeable side effects on the stomach. These two compounds are promising new NSAIDs.

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Section: Discussionmentioning

confidence: 99%

Drug Discovery of New Anti-Inflammatory Compounds by Targeting Cyclooxygenases

2022

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“…Furthermore, compound 110 exhibited the highest COX-2 inhibitory activity, and displayed the most potent cytotoxicity on MCF-7 cells, with an IC 50 value of 0.03 ± 0.01 µM which was comparable to that of doxorubicin (IC 50 of 0.062 ± 0.012 µM). Moreover, it can lead to apoptosis of MCF-7 cells, which may be mediated by upregulating the expression of Bax/Bcl-2 and activating the caspase-3 pathway 125 .…”

Section: Recent Development In Anti-inflammatory Agentsmentioning

confidence: 99%

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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“…Chen et al designed and synthesized 37 new resveratrol flavanol derivatives, of which compound 7f ( Figure 1 A) could inhibit the transduction of NF-κB cell signaling pathway caused by TLR4 activation and attenuate lipopolysaccharide-induced acute lung injury (ALI) in mice [ 22 ]. Indanones are also pharmacophores often embedded in more complex molecules with broad biological activities, including small molecules with anti-oxidative, antibacterial, and anti-inflammatory activities [ 24 ]. Man Kadayat et al designed and synthesized a series of indanone derivatives linked to pyridine, of which compounds 5b and 5d ( Figure 1 B) exhibited the most potent inhibitory activity against TNF-α-induced monocyte adhesion to colonic epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Novel Pterostilbene Derivatives That Might Treat Sepsis by Attenuating Oxidative Stress and Inflammation through Modulation of MAPKs/NF-κB Signaling Pathways

et al. 2021

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Sepsis remains one of the most common life-threatening illnesses that is characterized by a systemic inflammatory response syndrome (SIRS) and usually arises following severe trauma and various septic infections. It is still in urgent need of new effective therapeutic agents, and chances are great that some candidates can be identified that can attenuate oxidative stress and inflammatory responses. Pterostilbene, which exerts attractive anti-oxidative and anti-inflammatory activities, is a homologue of natural polyphenolic derivative of resveratrol. Starting from it, we have made several rounds of rational optimizations. Firstly, based on the strategy of pharmacophore combination, indanone moiety was introduced onto the pterostilbene skeleton to generate a novel series of pterostilbene derivatives (PIF_1–PIF_16) which could possess both anti-oxidative and anti-inflammatory activities for sepsis treatment. Then, all target compounds were subjected to their structure–activity relationships (SAR) screening of anti-inflammatory activity in mouse mononuclear macrophage RAW264.7 cell line, and their cytotoxicities were determined after. Finally, an optimal compound, PIF_9, was identified. It decreased the mRNA levels of lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2). We also found that the anti-inflammatory effects might be contributed by its suppression on the nuclear factor-κB (NF-κB) and MAPKs signaling pathway. Moreover, PIF_9 also demonstrated potent anti-oxidative activity in RAW264.7 macrophages and the sepsis mouse model. Not surprisingly, with the benefits mentioned above, it ameliorated LPS-induced sepsis in C57BL/6J mice and reduced multi-organ toxicity. Taken together, PIF_9 was identified as a potential sepsis solution, targeting inflammation and oxidative stress through modulating MAPKs/NF-κB.

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Design, synthesis and biological evaluation of novel indanone containing spiroisoxazoline derivatives with selective COX-2 inhibition as anticancer agents

Cited by 18 publications

References 36 publications

Drug Discovery of New Anti-Inflammatory Compounds by Targeting Cyclooxygenases

Drug Discovery of New Anti-Inflammatory Compounds by Targeting Cyclooxygenases

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

Discovery of Novel Pterostilbene Derivatives That Might Treat Sepsis by Attenuating Oxidative Stress and Inflammation through Modulation of MAPKs/NF-κB Signaling Pathways

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