Inhibition with the cyclooxynase-1 (COX-1) enzyme [168]. In 350 of sufferers. Nonetheless, oral Pyrotinib Protocol administration of indomethacin has been connected with systemic and nearby upper gastrointestinal side effects, for example erosions, ulcerative lesions, and petechial bleeding in the mucosa of the stomach [191]. Other research show that the oral administration of indomethacin in rats and humans causes ulcerative lesions in the gastric mucosa stemming in the generation of reactive oxygen species and lipid peroxidation [224]. 5-aminosalicyate (5-ASA) or its prodrugs (e.g., sulfasalazine, mesalazine, olsalazine, and balsalazide) have been employed as first-line medicines to treat ulcerative colitis for upkeep or remission [25,26]. These drugs can trigger some adverse effects, such as diarrhea, nausea, vomiting, headache, abdominal discomfort, fatigue, weakness, hepatic abnormalities, arthralgia, and myalgia [279]. Hence, it is actually essential to discover new option drugs capable of inhibiting myeloperoxidase (MPO) and producing an anti-inflammatory impact without the need of generating such serious adverse Lanabecestat Inhibitor effects [30,31]. For this goal, our research group has focused around the development of 5-ASA derivatives. Soon after becoming designed and synthesized in a earlier study, they were assessed in vitro and ex vivo [32,33]. The in vitro assays evidenced antioxidant properties when using the 2,2 –azino-bis(3-ethylbenzo thiazoline)-6-sulfonic acid (ABTS) and two,two -diphenyl-1-picrylhydrazyl (DPPH) solutions. Specifically, the compound 5-[(2E)3-bromo-3-carboxyprop-2-enoyl]amino-2-hydroxybenzoic acid (C1) (Figure 1), can minimize the production on the absolutely free radical DPPH about 90 in comparison to 5-ASA which generates a reduce reduction of this radical, becoming about 85 in the similar concentration (0.408 mM). Interestingly, C1 also exhibited anti-inflammatory activity within a 12-O-tetradecanoylphorbol acetate (TPA)-induced mouse ear edema model. As an inhibitor of MPO, its impact proved to become comparable to that of indomethacin based on an evaluation using the o-dianisidine method [32,33].Figure 1. Chemical structure of 5-[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino-2-hydroxybenzoic acid (C1).Inside the preclinical testing of a new drug candidate, the lack of in vivo activity is often attributed to inappropriate pharmacokinetic properties or toxicity (the formation of reactive metabolites) [34]. The aim with the current contribution was to take another step inside the preclinical evaluation of C1 by examining its acute toxicity and pharmacokinetic profile. Acute toxicity was explored together with the up-and-down OECD approach, although the pharmacokinetic profile was established by administering the compound to Wistar rats by way of the intravenous (i.v.), oral (p.o.), and intraperitoneal (i.p.) routes. After p.o. administration, the distribution of C1 was determined in organs and tissues. The boundMolecules 2021, 26,3 ofand unbound fraction of C1 in rat plasma was quantified plus the blood/plasma (BP) partition coefficient was calculated. 2. Benefits 2.1. Acute Toxicity of C1 Median lethal dose (LD50) values in Wistar rats have been 2000 mg/kg and 1098 mg/kg for p.o. and i.p. routes of administration, respectively. Animals did not show any indicators of toxicity together with the p.o. route. Through the necropsy, moreover, no macroscopic alterations were observed inside the liver, little intestine, colon, heart, spleen, stomach, or kidneys. Consequently, based on the Globally Harmonized Method (GHS) of Classification and Labeling of Chemical Pro.