Shtyrlin Nikita V, Sapozhnikov Sergey V, Koshkin Sergey A, Iksanova Alfiya G, Sabirov Arthur H, Kayumov Airat R, Nureeva Aliya A, Zeldi Marina I, Shtyrlin Yurii G
Research and Educational Center of Pharmacy, Kazan Federal University, Kazan, 420008, Russian Federation.
Med Chem. 2015;11(7):656-65. doi: 10.2174/1573406411666150504122930.
A series of 26 quaternary ammonium pyridoxine derivatives were synthesized and their cytotoxicity and antibacterial activities against clinically relevant bacterial strains were tested in vitro. The antibacterial activity of mono-ammonium salts increased with the rise of the lipophilicity and compound 3,3,5-trimethyl-8,8-dioctyl-1,7,8,9-tetrahydro-[1,3]dioxino[5,4-d]pyrrolo[3,4-b]pyridin-8-ium chloride (2d) reaches a maximum among them. Bis-ammonium salt of pyridoxine 4 with two dimethyloctylamine groups also demonstrated high antibacterial activity despite lower lipophilicity. The results of MTT assay indicated that HEK 293 cells were more sensitive than HSF to quaternary ammonium pyridoxine derivatives. Compounds 2d and 4 did not induce the damage of the DNA and might be of interest in the development of new antimicrobials.
合成了一系列26种季铵化吡哆醇衍生物，并在体外测试了它们对临床相关细菌菌株的细胞毒性和抗菌活性。单铵盐的抗菌活性随亲脂性的增加而增强，其中3,3,5-三甲基-8,8-二辛基-1,7,8,9-四氢-[1,3]二氧杂环戊烯并[5,4-d]吡咯并[3,4-b]吡啶-8-氯化铵（2d）的抗菌活性最高。含有两个二甲基辛胺基团的吡哆醇双铵盐4尽管亲脂性较低，但也表现出较高的抗菌活性。MTT分析结果表明，HEK 293细胞比HSF对季铵化吡哆醇衍生物更敏感。化合物2d和4不会诱导DNA损伤，可能在新型抗菌剂的开发中具有应用价值。
