ABSTRACT
Photodynamic therapy (PDT) is a potential approach to resolve antibiotic resistance, and phenylene/thiophene-ethynylene oligomers have been widely studied as effective antibacterial reagents. Oligomers with thiophene moieties usually exhibit good antibacterial activity under light irradiation and dark conditions. In the previous study, we verified that neutral oligo-p-phenylene-ethynylenes (OPEs) exhibit better antibacterial activity than the corresponding cationic ones; however, whether this regular pattern also operates in other kinds of oligomers such as oligo-thiophene-ethynylene (OTE) is unknown. Also, the antibacterial activity comparison of OTEs bearing cyclic and acyclic amino groups will offer useful information to further understand the role of amino groups in the antibacterial process and guide the antibacterial reagent design as amino groups affect the antibacterial activity a lot. We synthesized four OTEs bearing neutral or cationic, cyclic, or acyclic amino groups and studied their antibacterial activity in detail. The experimental results indicated that the OTEs exhibited better antibacterial activity than the OPEs, the neutral OTEs exhibited better antibacterial activity in most cases, and OTEs bearing cyclic amino groups exhibited better antibacterial activity than those bearing acyclic ones in most cases. This study provides useful guidelines for further antibacterial reagent design and investigations.
Subject(s)
Alkynes/pharmacology , Anti-Bacterial Agents/pharmacology , Thiophenes/pharmacology , Alkynes/chemistry , Alkynes/radiation effects , Alkynes/toxicity , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/radiation effects , Anti-Bacterial Agents/toxicity , Cell Line , Escherichia coli/drug effects , Humans , Hydrophobic and Hydrophilic Interactions , Light , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects , Thiophenes/chemistry , Thiophenes/radiation effects , Thiophenes/toxicityABSTRACT
Bacterial contamination and the spread of antibiotic-resistant bacteria demand alternate methods to deal with bacterial infections. With particular advantages, photodynamic therapy (PDT) is a promising approach. As a kind of photosensitizer for PDT, light-induced antibacterial compounds like oligo-p-phenylene-ethynylenes (OPEs) have been widely investigated while these studies mainly focus on OPEs with quaternary ammonium salts. In our previous study, OPEs with tertiary amino groups (T-OPEs) were reported to exhibit a better antibacterial activity than the corresponding quaternary ammonium salts, which make it important to develop T-OPEs and further investigate their structure-activity relationship. Additionally, the terminal structure of the reported OPEs mainly consists of quaternary ammonium salts or tertiary amino groups, which could not be linked to other materials. Thus, to develop more effective and multifunctional antibacterial agents, we designed and synthesized four unsymmetrical OPEs having terminal amino groups, which could be linked to other functional units by covalent bonds. Their antibacterial activity against Gram-positive and Gram-negative bacteria and the mechanism have been investigated. The OPEs showed effective biocidal activity under fiber light irradiation, and no dark killing was observed. The mechanism study indicates that OPEs could penetrate and perturb the cell membrane and generate ROS under light irradiation, both of which could influence their antibacterial activity. The penetrating ability of OPEs is partly dependent on their lipophilicity and the structure and composition of the cell membrane.