Indole-imidazolone derivatives as dual Mcl-1/COX-2 inhibitors: Design-oriented synthesis, molecular docking, and dynamics studies with potential anticancer and anti-inflammatory activities.

A novel series of indole-imidazolone derivatives (6a-l) was synthesized and evaluated for Mcl-1 inhibition. Compounds 6c, 6 g, and 6 k showed strong binding affinities (Ki = 0.02-0.

Optimization of pyrazole/1,2,4-triazole as dual EGFR/COX-2 inhibitors: Design, synthesis, anticancer potential, apoptosis induction and cell cycle analysis.

A novel series of pyrazol-4-yl-1,2,4-triazole-3-thiol derivatives 14a-l was designed, prepared and characterized by many spectroscopic techniques. All the novel compounds were screened for their anti-proliferative activity towards breast cancer cell line (MCF-7), colon cancer cell line (HT-29) and lung cancer cell line (A-549) utilizing celecoxib, erlotinib and osimertinib as standards. Compounds 14b, 14g and 14k were the most active towards HT-29, MCF-7 and A-549 cell lines, sequentially with IC = 1.

Discovery of novel thiazole derivatives containing pyrazole scaffold as PPAR-γ Agonists, α-Glucosidase, α-Amylase and COX-2 inhibitors; Design, synthesis and in silico study.

A novel series of thiazole derivatives with pyrazole scaffold 16a-l as hybrid rosiglitazone/celecoxib analogs was designed, synthesized and tested for its PPAR-γ activation, α-glucosidase, α-amylase and COX-2 inhibitory activities. Regarding the anti-diabetic activity, all compounds were assessed in vitro against PPAR-γ activation, α-glucosidase and α-amylase inhibition in addition to in vivo hypoglycemic activity (one day and 15 days studies). Compounds 16b, 16c, 16e and 16 k showed good PPAR-γ activation (activation % ≈ 72-79 %) compared to that of the reference drug rosiglitazone (74 %).

Discovery of novel pyrazole based Urea/Thiourea derivatives as multiple targeting VEGFR-2, EGFR, EGFR tyrosine kinases and COX-2 Inhibitors, with anti-cancer and anti-inflammatory activities.

A novel series of pyrazole derivatives with urea/thiourea scaffolds 16a-l as hybrid sorafenib/erlotinib/celecoxib analogs was designed, synthesized and tested for its VEGFR-2, EGFR, EGFR tyrosine kinases and COX-2, pro-inflammatory cytokines TNF-α and IL-6 inhibitory activities. All the tested compounds showed excellent COX-2 selectivity index in range of 18.04-47.

New pyrazolyl-thiazolidinone/thiazole derivatives as celecoxib/dasatinib analogues with selective COX-2, HER-2 and EGFR inhibitory effects: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis, molecular modelling and ADME studies.

Two new series of pyrazolyl-thiazolidinone/thiazole derivatives and were synthesised, merging the scaffolds of celecoxib and dasatinib. Compounds , and inhibit with S.I.

Design, synthesis, and pharmacological evaluation of novel and selective COX-2 inhibitors based on celecoxib scaffold supported with in vivo anti-inflammatory activity, ulcerogenic liability, ADME profiling and docking study.

Four new series of 1,2,4 triazole derivatives 4a,b 5a-d, 6a-f, and 7a,b possessing methylsulphonylphenyl moiety as COX-2 pharmacophore were designed and synthesized. The target compounds were prepared and evaluated in-vitro against COX-1 and COX-2 enzymes. Compounds 4a, 5b, 6a, and 7a showed the highest selectivity towards the COX-2 enzyme (S.

Optimization of pyrazole-based compounds with 1,2,4-triazole-3-thiol moiety as selective COX-2 inhibitors cardioprotective drug candidates: Design, synthesis, cyclooxygenase inhibition, anti-inflammatory, ulcerogenicity, cardiovascular evaluation, and molecular modeling studies.

The cardiovascular side effects associated with COX-2 selective drugs were the worst for coxibs leading to their withdrawal from the market a few years after their discovery. Therefore, the design of new series of pyrazole (4a,b 5a,b, 7a,b, 9a,b, 10a-h, and 11a-f) substituted with a triazole moiety as selective COX-2 inhibitors with cardioprotective effect was aimed in this paper. The target compounds were prepared and evaluated in-vitro against COX-1 and COX-2 enzymes.