New 1,2,3-triazole/1,2,4-triazole hybrids linked to oxime moiety as nitric oxide donor selective COX-2, aromatase, B-RAF^V600E and EGFR inhibitors celecoxib analogs: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis and molecular modeling study.

ABSTRACT: A new series of bis-triazole 19a-l was synthesised for the purpose of being hybrid molecules with both anti-inflammatory and anti-cancer activities and assessed for cell cycle arrest, NO release. Compounds 19c, 19f, 19h, 19 l exhibited COX-2 selectivity indexes in the range of 18.48 to 49.38 compared to celecoxib S.I. = 21.10), inhibit MCF-7 with IC₅₀ = 9-16 μM compared to tamoxifen (IC₅₀ = 27.9 μM). and showed good inhibitory activity against HEP-3B with IC₅₀ = 4.5-14 μM compared to sorafenib (IC₅₀ = 3.5 μM) (HEP-3B). Moreover, derivatives 19e, 19j, 19k, 19 l inhibit HCT-116 with IC₅₀ = 5.3-13.7 μM compared to 5-FU with IC₅₀ = 4.8 μM (HCT-116). Compounds 19c, 19f, 19h, 19 l showed excellent inhibitory activity against A549 with IC₅₀ = 3-4.5 μM compared to 5-FU with IC₅₀ = 6 μM (A549). Compounds 19c, 19f, 19h, 19 l inhibit aromatase (IC₅₀ of 22.40, 23.20, 22.70, 30.30 μM), EGFR (IC₅₀ of 0.112, 0.205, 0.169 and 0.066 μM) and B-RAF^V600E (IC₅₀ of 0.09, 0.06, 0.07 and 0.05 μM).

SUBMITTER: Fadaly WAA 

PROVIDER: S-EPMC11003496 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature