Background The search for new antitumour drugs is creating new pyrimidine antimetabolites that will affect the structure and functions of nucleonic acids. It is known that some tumours metabolise uracil more actively than normal cells. Therefore 5-FU (5-fluorouracil) and its derivatives will act as substrates and/or inhibitors of ferments and will be taken up by tumour cells.
Lectins are multivalent proteins that interact with glycosylated surfaces and nanomaterials.
Purpose To report the synthesis, characterisation, toxicity and antitumour activity of a new chemical-biological adduct: bacterial lectin (Bacillus subtilis 668 IMV) - bis-derivative of 5-FU).
Materials and methods Object of the investigation: new bis derivative of 5-FU, its adduct with bacterial lectin (Bacillus subtilis 668 IMV). White Wistar male rats mice (300 animals) and an experimental tumour model (LS Plissa) were used as described below. The experimental tumours used for investigations were obtained from the cancer material bank of the Oncological Centre of the Russian Federation’s Academy of Medical Sciences. The efficiency parameter [% of growth relaxation of LS Plissa, (volume, mass)] was less than 50%.
The new bis-derivative of 5-FU (bis-5-FU) and halothane was obtained under phase-transfer conditions with catalysis by an 18-crown-6 complex. The new chemical-biological adducts were created by joining bis-derivative of 5-FU and Bacillus subtilis 668 IMV (lectin 668).
Results Data from toxicity studies of the compounds confirmed their low toxicity: LD50 of lectin 668 is 89 mg/kg, LD50 of bis-5-FU is 125 mg/kg, LD50 of the adduct (lectin 668-bis-5-FU) is 137 mg/kg. The adduct (lectin 668- bis-5-FU) was found to have a strongly antitumour effect on LS Plissa – 62.8% (for 5-FU, the control is 55%).
Conclusions Derivatives of 5-FU and their adducts with bacterial lectin (B. subtilis 668 IMV) are substances for further investigation as potential drugs with antitumour activity.
No conflict of interest.
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