Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Profesor García González 2, 41012 Sevilla, Spain.
Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Profesor García González 2, 41012 Sevilla, Spain.
Mater Sci Eng C Mater Biol Appl. 2021 Jun;125:112113. doi: 10.1016/j.msec.2021.112113. Epub 2021 Apr 17.
Novel linear cationic poly(amide aminotriazole)s (PATnD) with secondary amine groups in the backbone were obtained by using azide-alkyne 1,3-dipolar cycloaddition reactions: metal- and solvent-free (thermal conditions, PATTnD) or copper(I)-catalyzed (Sharpless conditions, PATCnD). PATnD were investigated in vitro against strains of E. coli, P. aeruginosa, S. aureus, and S. epidermidis. Hemolytic activity was tested using human red blood cells (hRBC), and very low or no hemolytic activity was observed. The cytotoxicity of PATnD polymers against Human Gingival Fibroblasts (HGnF) cells was concentration-dependent, and significant differences between PATT1D and PATC1D were observed. The ability of these polymers to induce resistance against both Gram-positive and Gram-negative bacteria was also assessed. Studied bacterial strains acquired resistance to catalytic polymers (PATCnD) in initial passages meanwhile resistance to thermal polymers (PATTnD) appears in later passages, being the increase of the minimum inhibitory concentration lower than in catalytic polymers. This result, together with the higher biocidal capacity of thermal polymers compared to catalytic ones, seems to suggest an influence of the regiospecificity of the polymers on their antibacterial characteristics. This study also demonstrates that PAT1D polymers, which do not appear to have strong hydrophobic residues, can exert significant antimicrobial activity against Gram-positive bacteria such as S. epidermidis. This pair of polymers, PATC1D and PATT1D, displays the greatest antimicrobial activity while not causing significant hemolysis along with the lowest susceptibility for resistance development of the polymers evaluated.
新型线性阳离子聚（酰胺叠氮化物）（PATnD）具有在骨架中仲胺基团，通过叠氮化物-炔烃 1,3-偶极环加成反应获得：无金属和无溶剂（热条件，PATTnD）或铜（I）催化（Sharpless 条件，PATCnD）。PATnD 对大肠杆菌、铜绿假单胞菌、金黄色葡萄球菌和表皮葡萄球菌进行了体外测试。用人类红细胞（hRBC）测试溶血活性，观察到非常低或没有溶血活性。PATnD 聚合物对人牙龈成纤维细胞（HGnF）细胞的细胞毒性呈浓度依赖性，PATT1D 和 PATC1D 之间存在显著差异。还评估了这些聚合物对革兰氏阳性和革兰氏阴性细菌的诱导抗性能力。研究的细菌菌株在初始传代中对催化聚合物（PATCnD）产生了抗性，而在随后的传代中对热聚合物（PATTnD）产生了抗性，最低抑菌浓度的增加低于催化聚合物。这一结果，再加上热聚合物比催化聚合物具有更高的杀菌能力，似乎表明聚合物的区域特异性对其抗菌特性有影响。这项研究还表明，PAT1D 聚合物似乎没有强疏水性残基，对革兰氏阳性细菌如表皮葡萄球菌具有显著的抗菌活性。这对聚合物，PATC1D 和 PATT1D，显示出最大的抗菌活性，同时不会引起显著的溶血，并且评估的聚合物对抗性发展的敏感性最低。
