Synthesis and biological evaluation of benzamide‐chalcone hybrids as potential c‐Met kinase and COX‐2 inhibitors

Bhojwani, Heena R.; Begwani, Khushboo V.; Bhor, Vikrant M.; Bedi, Parul; Balasinor, Nafisa; Raut, Sanketa; Joshi, Urmila J.

doi:10.1002/ardp.202200405

Cited by 3 publications

(1 citation statement)

References 69 publications

(91 reference statements)

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“…Previous research has demonstrated that the overexpression of COX-2, and subsequent production of PGE 2 , can enhance cell motility in colorectal cancer cell lines [ 12 ]. Various studies examined the antimigratory potential of COX-2 inhibitors [ 12 , 13 ]. For the natural dual COX-2 and 5-LOX inhibitor psoralidin, potent cytotoxicity against HT-29 and MCF-7 cancer cell lines, as well as attenuation of fibroblast migration caused by radiation therapy, was demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma

Bošković,

Dobričić,

Keta

et al. 2024

Pharmaceutics

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Apart from cytotoxicity, inhibitors of the COX-2 enzyme have demonstrated additional effects important for cancer treatment (such as radiosensitization of tumor cells and cell antimigratory effects); however, the relationship between the inhibition of other inflammation-related enzyme 5-LOX inhibitors and anticancer activity is still not well understood. In our study, the cytotoxicity of thirteen COX-2 and 5-LOX inhibitors previously presented by our group (1–13) was tested on three cancer cell lines (HCT 116, HT-29 and BxPC-3) and one healthy cell line (MRC-5). Compounds 3, 5, 6 and 7 showed moderate cytotoxicity, but good selectivity towards cancer cell lines. IC50 values were in the range of 22.99–51.66 µM (HCT 116 cell line), 8.63–41.20 µM (BxPC-3 cell line) and 24.78–81.60 µM (HT-29 cell line; compound 7 > 100 µM). In comparison to tested, commercially available COX-2 and 5-LOX inhibitors, both cytotoxicity and selectivity were increased. The addition of compounds 6 and 7 to irradiation treatment showed the most significant decrease in cell proliferation of the HT-29 cell line (p < 0.001). The antimigratory potential of the best dual COX-2 and 5-LOX inhibitors (compounds 1, 2, 3 and 5) was tested by a wound-healing assay using the SW620 cell line. Compounds 1 and 3 were singled out as compounds with the most potent effect (relative wound closure was 3.20% (24 h), 5,08% (48 h) for compound 1 and 3.86% (24 h), 7.68% (48 h) for compound 3). Considering all these results, compound 3 stood out as the compound with the most optimal biological activity, with the best dual COX-2 and 5-LOX inhibitory activity, good selectivity towards tested cancer cell lines, significant cell antimigratory potential and a lack of toxic effects at therapeutic doses.

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Section: Introductionmentioning

confidence: 99%

Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma

Bošković,

Dobričić,

Keta

et al. 2024

Pharmaceutics

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Mechanistic and kinetic aspects of Natamycin interaction with serum albumin using spectroscopic and molecular docking methods

Azimirad

Javaheri-Ghezeldizaj

Yekta

et al. 2023

Arabian Journal of Chemistry

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Dual-Target Inhibitors Based on COX-2: A Review from Medicinal Chemistry Perspectives

Zhang,

Zhu,

et al. 2023

Future Med. Chem.

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Inhibitors of COX-2 constitute a class of anti-inflammatory analgesics, showing potential against certain types of cancer. However, such inhibitors are associated with cardiovascular toxicity. Moreover, although single-target molecules possess specificity for particular targets, they often lead to poor safety, low efficacy and drug resistance due to compensatory mechanisms. A new generation of dual-target drugs that simultaneously inhibit COX-2 and another target is showing strong potential to treat cancer or reduce adverse cardiac effects. The present perspective focuses on the structure and functions of COX-2, and its role as a therapeutic target. It also explores the current state and future possibilities for dual-target strategies from a medicinal chemistry perspective.

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Synthesis and biological evaluation of benzamide‐chalcone hybrids as potential c‐Met kinase and COX‐2 inhibitors

Cited by 3 publications

References 69 publications

Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma

Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma

Mechanistic and kinetic aspects of Natamycin interaction with serum albumin using spectroscopic and molecular docking methods

Dual-Target Inhibitors Based on COX-2: A Review from Medicinal Chemistry Perspectives

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