This study investigated the analgesic, anti‐inflammatory, and antiulcer activities of thioxo‐thiazolidinone derivatives ( 2a , 2b , and 2c ) and synthesized from glycine, alanine, and phenylalanine. Male Wistar rats (240–290 g; n = 5/group) and Swiss mice (25–35 g; n = 6/group) were used for anti‐inflammatory and analgesic tests, respectively, under approved ethical protocol (CEUA/UFRN n ° 004/2012) and following the ARRIVE and 3 Rs guidelines. Analgesic activity was assessed using the hot plate and acetic acid‐induced writhing tests; anti‐inflammatory effects were evaluated in carrageenan‐induced paw edema and peritonitis models; and antiulcer potential was tested against indomethacin‐induced gastric lesions. In the rat paw edema model, Compound 2c (200 mg/kg, p.o.) and sodium diclofenac reduced edema. In the peritonitis model, Compound 2c decreased the number of leukocytes ( p < 0.05), similar to indomethacin ( p < 0.05). In the hot plate test, Compound 2c (200 mg/kg) produced significant antinociceptive effects at 30, 90, and 120 min ( p < 0.05), partially reversed by naloxone, suggesting opioid involvement. Compounds 2a (50 mg/kg:, p < 0.01) and 2b (50 mg/kg:; 100 mg/kg: p < 0.05) and indomethacin at a dose of 10 mg/kg ( p < 0.05) significantly reduced writhing responses comparable to control. Unlike indomethacin (ulcer score: 63.4 ± 5.2), all compounds showed minimal gastric damage (scores ≤ 8.1 ± 1.3, p < 0.001). In silico analysis revealed that 2c exhibited strong binding affinities to PLA2 (−10.38 kcal/mol) and ADA (−9.78 kcal/mol), supporting its pharmacological profile. Together, these quantitative and comparative findings demonstrate that 2c exhibits potent analgesic and anti‐inflammatory activities with markedly reduced gastric toxicity, reinforcing its potential as a safe multitarget anti‐inflammatory candidate.
Araújo et al. (Thu,) studied this question.