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

• Published in: Journal of enzyme inhibition and medicinal chemistry 2023-12, Vol.38 (1), p.2290461
• Main Authors: Fadaly, Wael A A, Nemr, Mohamed T M, Zidan, Taha H, Mohamed, Fatma E A, Abdelhakeem, Marwa M, Abu Jayab, Nour N, Omar, Hany A, Abdellatif, Khaled R A
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents - pharmacology; Antineoplastic Agents - pharmacology; Apoptosis; Aromatase - metabolism; Celecoxib; Cell Line, Tumor; Cyclooxygenase 2 - metabolism; ErbB Receptors - metabolism; Fluorouracil; Molecular Docking Simulation; Molecular Structure; Nitric Oxide Donors - pharmacology; Structure-Activity Relationship; Triazoles - pharmacology
• ISSN: 1475-6366; 1475-6374
• DOI: 10.1080/14756366.2023.2290461

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).