5-Fluorouracil (5-FU) is an antimetabolite widely prescribed in cancer treatments, but its use in highly proliferative tissues can cause significant problems such as mucositis. Bacillus clausii is a probiotic commonly used for protection against acute diarrhea, gastrointestinal dysbiosis and inflammatory bowel diseases. We investigated the effect of B. clausii on 5-FU intestinal mucositis in mice. B. clausii was administered concomitantly with 5-FU on the first day and alone for the other two days. After the third day of 5-FU (450 mg/kg, ip), the animals were euthanized. Ileum samples were removed for evaluation for histopathological and biochemical analyses (myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), catalase (CAT), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α). In addition, we investigated gastric emptying and intestinal transit, intestinal permeability, intestinal smooth muscle contractility, transepithelial electrical resistance and intestinal transport of water and electrolytes. B. clausii reduced histopathological scores and increased the villus/crypt ratio in all intestinal segments after mucositis. B. clausii attenuated 5-FU-induced weight loss. The probiotic treatment increased GSH levels, reduced MPO and CAT activity, and also reduced MDA, IL-1β and TNF-α levels. B. clausii attenuated the delay in gastric emptying, water and electrolyte secretion and intestinal hypercontractility, and increased 5-FU-induced intestinal permeability. Thus, our data suggest that B. clausii may be a potential candidate for the treatment of chemotherapy-induced intestinal mucositis.

Acylhydrazones are still an important framework to the design of new bioactive compounds. As treatment of chronic pain represents a clinical challenge, we decided to modify the structure of LASSBio-1514 (1), previously described as anti-inflammatory and analgesic prototype. Applying the homologation as a strategy for molecular modification, we designed a series of cyclopentyl- (2a–e), cyclobutyl- (3a–e), and cyclopropylacylhydrazones (4a–e) that were synthetized and evaluated in murine models of inflammation and pain. A comparison of their in silico physicochemical and drug-like profile was conducted, as well as their anti-inflammatory and analgesic effect. Compounds 4a (LASSBio-1755) and 4e (LASSBio-1757) displayed excellent in silico drug-like profiles and were identified as new analgesic lead-candidates in acute and chronic model of pain, through oral administration.