Dual Anti-Cancer and Anti-Inflammatory Activity of Some New Benzofuran-Thiazole Hybrids With Promising COX-2...

Chronic inflammation, arising from unregulated inflammatory responses to tissue damage, is linked to 25% of all cancers. Some new benzofuran-thiazole hybrids, H1-H4, were prepared herein and assessed as dual anticancer and anti-inflammatory agents. All hybrids tested displayed good potency against Caco2 cells. Particularly, H4 outperformed doxorubicin in potency, with an IC₅₀ of 0.24 μM. Moreover, H2 and H3 exhibited excellent antiproliferative activity against RAW 264.7 cells, which was found comparable to celecoxib, with IC₅₀ values of 160.75 and 115.76 μM, respectively. The safety of the new hybrids was evaluated against HFB4 cells, as we found that H2 and H3 showed superior selectivity against cancer cells. H2 and H3 were found to significantly increase apoptosis in RAW 264.7 cells, confirming their potential as cytotoxic agents. The anti-inflammatory efficacy of some hybrids was screened. The inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells was measured to assess the anti-inflammatory effects, where H2 showed significant inhibition at a dose of 100 µM. Also, H3 exhibited comparable cyclooxygenase-2 (COX-2) inhibitory potency to celecoxib with an IC₅₀ of 0.69 μM. At a dose of 1/20 LD₅₀, both H2 and H3 were safe for kidney function in an animal model. However, H2 was safer for gastric tissue, while H3 showed adverse gastric effects at this same concentration. The molecular docking of both hybrids displayed important binding modes with the mouse COX-2 (PDB ID: 7O37).