Fragment merging approach for the design of thiazole/thiazolidine clubbed pyrazoline derivatives as anti-inflammatory agents: Synthesis, biopharmacological evaluation and molecular modeling studies

Design, Synthesis, and Biological Evaluation of Novel Phenoxy Acetic Acid Derivatives as Selective COX-2 Inhibitors Coupled with Comprehensive Bio-Pharmacological Inquiry, Histopathological Profiling, and Toxicological Scrutiny

“…In continuation of our previous research on developing selective COX-2 candidates [24,25], we reported phenoxyacetic acid (XIV), which revealed potent COX-2 activity compared to celecoxib with an IC 50 of 0.06 µM, due to the coupling between the chlorophenyl structural motif and the p-phenoxy acetic acid moiety (Figure 1).…”

New Thiazolyl-Pyrazoline Derivatives as Potential Dual EGFR/HER2 Inhibitors: Design, Synthesis, Anticancer Activity Evaluation and In Silico Study

“…For compound VI, it displayed antiproliferative activity for the breast cancer T-47D cell line with inhibition activity toward EGFR (IC 50 = 83 nM) [42] (Figure 1). According to the above data and in continuation of our scholarly interest in the chemistry of thiazolyl-pyrazolines and their biological activities [43][44][45], especially as possible anticancer agents [27,46,47], our objective was to enhance and modify a novel series of innovative thiazolyl-pyrazoline derivatives (4a-d, 5a-d, 6a, b, 7a-d, 8a, b, and 10a, b) as According to the above data and in continuation of our scholarly interest in the chemistry of thiazolyl-pyrazolines and their biological activities [43][44][45], especially as possible anticancer agents [27,46,47], our objective was to enhance and modify a novel series of innovative thiazolyl-pyrazoline derivatives (4a-d, 5a-d, 6a, b, 7a-d, 8a, b, and 10a, b) as potential dual-inhibitors against EGFR/HER2 with possible enhancement of their antiproliferative activities depending on introducing bioactive fragments like aryl-diazinyl, arylidene, isatin, or coumarin substitutions into the thiazole-pyrazoline combination as the core center (Figure 1). So, the basis and rationale of the design of target compounds as potential anticancer agents for breast cancer depend on the hybridization of the two bioactive scaffolds thiazole and pyrazoline which give greater anticancer activity by optimization of previous compounds by adding extra hydrophobic binding site and choosing the most active substituents (Cl and OCH 3 ) in the previous work [48] which depends on inhibiting MCF-7 which represent a very important candidate as they are used ubiquitously in research for estrogen receptor (ER)-positive breast cancer cell experiments and many sub-clones, which have been established, represent different classes of ER-positive tumors with varying nuclear receptor expression levels.…”

“…For chemistry apparatus, see the supplementary file (page 65) Carbothioamides 1a, b [40,43], N-arylpropanehydrazonoyl chlorides 2a-d [44], and 2-bromoacetyl coumarin 9 [45] were prepared following the reported methods. IR ν max /cm −1 3077 (N-H), 3001 (C-H Ar), 2962 (C-H Ali.…”