Antibacterial and Anticancer Activity, Acute Toxicity, and Solubility of Co-crystals of 5-Fluorouracil and Trimethoprim

Abstract

5-Fluorouracil is mainly used for the treatment of tumors and has relatively high toxicity. Trimethoprim is a common broad-spectrum antibiotic agent with extremely poor water solubility. We hoped to solve these problems by synthesizing cocrystals (compound 1) of 5-fluorouracil and trimethoprim. Solubility tests showed that the solubility of compound 1 was improved compared to that of trimethoprim. In vitro anticancer activity tests of compound 1 showed higher activity against human breast cancer cells than 5-fluorouracil. Acute toxicity showed that its toxicity was much lower than that of 5-fluorouracil. In the test of anti-Shigella dysenteriae activity, compound 1 showed much stronger antibacterial activity than trimethoprim.

Cocrystal of Naringenin and Norfloxacin: Crystal Transformation, Solubility, and Antibacterial and Anticancer Activities

“…1,2 In recent years, drug cocrystals have made great progress in modifying drug properties, such as improving the properties, stability, and solubility of drugs without affecting their pharmacological properties. 3,4 Since the first ionic cocrystal drug "sacubitril + valsartan" for the treatment of heart failure was approved by the FDA in 2015, cocrystals such as tramadol Hydrochloride− Celecoxib and egliptin-L-pyroglutamic acid have been discovered. The drug cocrystal of tramadol hydrochloride and celecoxib reduces the toxic and addictive properties of tramadol hydrochloride and enhances the analgesic effect of celecoxib.…”

“…Pharmaceutical cocrystals are novel solid forms based on the principles of crystal engineering and supramolecular chemistry, which consist of active pharmaceutical ingredients (APIs) and cocrystal formers (CCFs) bonded in a certain ratio within a crystal lattice through noncovalent bonds. , In recent years, drug cocrystals have made great progress in modifying drug properties, such as improving the properties, stability, and solubility of drugs without affecting their pharmacological properties. , Since the first ionic cocrystal drug “sacubitril + valsartan” for the treatment of heart failure was approved by the FDA in 2015, cocrystals such as tramadol Hydrochloride–Celecoxib and egliptin- l -pyroglutamic acid have been discovered. The drug cocrystal of tramadol hydrochloride and celecoxib reduces the toxic and addictive properties of tramadol hydrochloride and enhances the analgesic effect of celecoxib. , A drug cocrystal not only significantly improves the deficiencies in the physicochemical properties of two drugs but also realizes the concept of combined medicine with better efficacy, which makes it more promising and valuable in the pharmaceutical market.…”