Synthesis, cytotoxicity, and antimicrobial activity of triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl analogues of pyrimidine nucleosides bearing N-acetyl-β-D-glucosamine residue.

Abstract

A series of triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl analogues of pyrimidine nucleosides was synthesized. In these compounds a TPP cation was attached via a decamethylene linker to the atom N-3 of the nucleic base (uracil, thymine) or its analog (6-methyluracil), and the N-acetyl-β-D-glucosamine residue with protected (or unprotected) hydroxyl groups was attached via a 1,2,3-triazolylmethyl or 1,2,3-triazolylbutyl linker to the atom N-1 of the listed pyrimidine derivatives. All synthesized TPP-conjugates caused the death of MCF-7 cancer cells within the range IC50 = 1.9-27 µM and PC-3 cancer cells within the range IC50 = 2.6-19.4 µM. Bacteriostatic and bactericidal activity against Gram-positive bacteria Staphylococcus aureus, Bacillus cereus, and methicillin-resistant strains of S. aureus MRSA-1 and MRSA-2 was detected for several TPP-conjugates within the concentration range (MIC and MBC) from 7.8 to 15.6 µM.