New 1,2,3-triazole/1,2,4-triazole hybrids linked to oxime moiety as nitric oxide donor selective COX-2, aromatase, B-RAFV600E and EGFR inhibitors celecoxib analogs: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis and molecular modeling study

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 mu M compared to tamoxifen (IC50 = 27.9 mu M). and showed good inhibitory activity against HEP-3B with IC50 = 4.5-14 mu M compared to sorafenib (IC50 = 3.5 mu M) (HEP-3B). Moreover, derivatives 19e, 19j, 19k, 19 l inhibit HCT-116 with IC50 = 5.3-13.7 mu M compared to 5-FU with IC50 = 4.8 mu M (HCT-116). Compounds 19c, 19f, 19h, 19 l showed excellent inhibitory activity against A549 with IC50 = 3-4.5 mu M compared to 5-FU with IC50 = 6 mu M (A549). Compounds 19c, 19f, 19h, 19 l inhibit aromatase (IC50 of 22.40, 23.20, 22.70, 30.30 mu M), EGFR (IC50 of 0.112, 0.205, 0.169 and 0.066 mu M) and B-RAF(V600E) (IC50 of 0.09, 0.06, 0.07 and 0.05 mu M).