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

A new series of bis-triazole 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 , , , 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 IC = 9-16 μM compared to tamoxifen (IC = 27.9 μM). and showed good inhibitory activity against HEP-3B with IC = 4.5-14 μM compared to sorafenib (IC = 3.5 μM) (HEP-3B). Moreover, derivatives , , , inhibit HCT-116 with IC = 5.3-13.7 μM compared to 5-FU with IC = 4.8 μM (HCT-116). Compounds , , , showed excellent inhibitory activity against A549 with IC = 3-4.5 μM compared to 5-FU with IC = 6 μM (A549). Compounds inhibit aromatase (IC of 22.40, 23.20, 22.70, 30.30 μM), EGFR (IC of 0.112, 0.205, 0.169 and 0.066 μM) and B-RAF (IC of 0.09, 0.06, 0.07 and 0.05 μM).