Discovery of small molecule acting as multitarget inhibitor of colorectal cancer by simultaneous blocking of the key COX-2, 5-LOX and PIM-1 kinase enzymes

El-Miligy, Mostafa M.M.; Al-Kubeisi, Ahmed K; El-Zemity, Saad R.; Nassra, Rasha A.; Abu‐Serie, Marwa M.; Hazzaa, A. A. B.

doi:10.1016/j.bioorg.2021.105171

Cited by 15 publications

(17 citation statements)

References 36 publications

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“…Moreover, compounds 5g and 5e induced apoptosis in CRC cell lines and induced caspase activation. Compounds 5d, 5g, and 5e inhibited PIM1 and PIM2 kinase, which was comparable to the reference staurosporine ( El-Miligy et al, 2021 ).…”

Section: Quercetin and Gastrointestinal Cancersupporting

confidence: 61%

Application of Quercetin in the Treatment of Gastrointestinal Cancers

et al. 2022

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Many cellular signaling pathways contribute to the regulation of cell proliferation, division, motility, and apoptosis. Deregulation of these pathways contributes to tumor cell initiation and tumor progression. Lately, significant attention has been focused on the use of natural products as a promising strategy in cancer treatment. Quercetin is a natural flavonol compound widely present in commonly consumed foods. Quercetin has shown significant inhibitory effects on tumor progression via various mechanisms of action. These include stimulating cell cycle arrest or/and apoptosis as well as its antioxidant properties. Herein, we summarize the therapeutic effects of quercetin in gastrointestinal cancers (pancreatic, gastric, colorectal, esophageal, hepatocellular, and oral).

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Section: Quercetin and Gastrointestinal Cancersupporting

confidence: 61%

Application of Quercetin in the Treatment of Gastrointestinal Cancers

et al. 2022

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“…The aforementioned in vitro data revealed that the ibuprofen analogue 6b , the salicylic acid analogue 6j together with the diclofenac analogue 6e expressed excellent human COX-2 selectivity and inhibitory activities. Hence, an in vivo carrageenan-induced paw edema bioassay in mice was implemented [ 24 , 25 ] on the three analogues 6b , 6j and 6e in order to fulfill their anti-inflammatory potency. The capacity of the targeted compounds to relieve mouse paw edema thickness (mm) during specified time intervals (2, 4, 6 and 8 h) after injecting carrageenan was measured, and the protection percent against edema (anti-inflammatory activity; AI%) was calculated.…”

Section: Resultsmentioning

confidence: 99%

Rational Design and Synthesis of New Selective COX-2 Inhibitors with In Vivo PGE2-Lowering Activity by Tethering Benzenesulfonamide and 1,2,3-Triazole Pharmacophores to Some NSAIDs

et al. 2022

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New selective COX-2 inhibitors were designed and synthesized by tethering 1,2,3-triazole and benzenesulfonamide pharmacophores to some NSAIDs. Compounds 6b and 6j showed higher in vitro COX-2 selectivity and inhibitory activity (IC50 = 0.04 µM and S.I. = 329 and 312, respectively) than celecoxib (IC50 = 0.05 µM and S.I. = 294). Compound 6e revealed equipotent in vitro COX-2 inhibitory activity to celecoxib. Furthermore, 6b and 6j expressed more potent relief of carrageenan-induced paw edema thickness in mice than celecoxib, with ED50 values of 11.74 µmol/kg and 13.38 µmol/kg vs. 16.24 µmol/kg, respectively. Compounds 6b and 6j inhibited the production of PGE2 with a % inhibition of PGE2 production of 90.70% and 86.34%, respectively, exceeding celecoxib’s percentage (78.62%). Moreover, 6b and 6j demonstrated a gastric safety profile comparable to celecoxib. In conclusion, compounds 6b and 6j better achieved the target goal as more potent and selective COX-2 inhibitors than celecoxib in vitro and in vivo.

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“…The docking studies in the active site of target enzymes were supported by the biological results. In conclusion, Compound 73g was found as effective inhibitor of three targets that lead to inhibition of human colorectal cancer cell proliferation [67].…”

Section: Anti-inflammatory and Analgesic Propertiesmentioning

confidence: 89%

“…Additionally, Compounds 5c, 5d, 5i, 5r and 5s were 2-fold more active ascorbic acid with IC50 values in the range of 12. 67 Sava et al conducted synthesis of thiazolidin-4-one-indometacin hybrids and ev ated their antioxidant activity with use of DPPH radical scavenging method [21]. The active derivatives from whole series were Compounds 7 and 8 with IC50 values 0.54 ± and 1.82 ± 0.05 mM, respectively (Figure 3).…”

Section: Biological Activities Of Thiazolidin-4-ones 21 Antioxidant Activitymentioning

confidence: 99%

The Bioactivity of Thiazolidin-4-Ones: A Short Review of the Most Recent Studies

Mech

Kurowska

Trotsko

2021

IJMS

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Thiazolidin-4-ones is an important heterocyclic ring system of a pharmacophore and a privileged scaffold in medicinal chemistry. This review is focused on the latest scientific reports regarding biological activities of thiazolidin-4-ones published in 2020 and 2021. The review covers recent information about antioxidant, anticancer, anti-inflammatory, analgesic, anticonvulsant, antidiabetic, antiparasitic, antimicrobial, antitubercular and antiviral properties of thiazolidin-4-ones. Additionally, the influence of different substituents in molecules on their biological activity was discussed in this paper. Thus, this study may help to optimize the structure of thiazolidin-4-one derivatives as more efficient drug agents. Presented information may be used as a practical hint for rational design of new small molecules with biological activity, especially among thiazolidin-4-ones.

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Discovery of small molecule acting as multitarget inhibitor of colorectal cancer by simultaneous blocking of the key COX-2, 5-LOX and PIM-1 kinase enzymes

Cited by 15 publications

References 36 publications

Application of Quercetin in the Treatment of Gastrointestinal Cancers

Application of Quercetin in the Treatment of Gastrointestinal Cancers

Rational Design and Synthesis of New Selective COX-2 Inhibitors with In Vivo PGE2-Lowering Activity by Tethering Benzenesulfonamide and 1,2,3-Triazole Pharmacophores to Some NSAIDs

The Bioactivity of Thiazolidin-4-Ones: A Short Review of the Most Recent Studies

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