抗生素耐药是临床医学难题，慢性难愈合创面是耐药菌感染的突出代表。已有文献研究表明慢性难愈合创面感染既需要抑制耐药菌，又需要抗炎治疗，提示研发既抗菌又抗炎的新药可能是治疗此类感染的有效策略。本课题组前期研究发现木豆素合成类似物具有优良的抗菌活性，且能通过激动PPARgamma发挥抗炎作用，可作为抗菌抗感染的先导物。但目前该类化合物抗菌作用靶标尚不清楚，且对革兰氏阴性菌的抑制效果较差。本课题将进一步对木豆素进行系统结构改造，设计合成抗革兰氏阳性菌、阴性菌以及抗细菌生物膜的广谱抗耐药菌化合物；通过靶标垂钓和系统研究阐明该类化合物的抗菌作用靶标和作用机制。同时，基于该类化合物具有抗菌及抗炎双重作用，探索研究该类化合物作为慢性难愈合创面抗感染药物的可行性，以期发现新药苗头化合物。本课题通过系统研究将揭示木豆素合成类似物抗耐药菌的构效关系，为研究设计新型抗耐药菌感染药物提供重要的科学基础。

Antibiotic resistance is a clinical problem, especially the drug-resistant bacterial infection in chronic wounds. Accumulated literatures show that the treatment of chronic wounds that accompanied by drug-resistant bacterial infection requires both antibacterial and anti-inflammatory, which suggests that design and development of novel agents that with both antibacterial and anti-inflammatory activities is likely to be an effective strategy for the treatment of such infections. Our previous studies found that the synthetic cajaninstilbene acid analogues show excellent antimicrobial activity, and they can act as PPARgamma agonist to exhibit anti-inflammatory effects, it is suggested that cajaninstilbene acid could probably be used as antibacterial leading compound. While their antibacterial target and action mechanism are not clear yet, and they show poor inhibitory effect against the gram-negative bacteria. Therefore, this project will design and synthesize series of new cajaninstilbene acid derivatives to get broad-spectrum antibacterial compounds with effects against both gram-positive and gram-negative pathogens as well as bacterial biofilm inhibitory effect, and try to clarify their antibacterial target and action mechenism by target fishing using probe molecule. Meanwhile, as our synthetic cajaninstilbene acid analogues show both antibacterial and anti-inflammatory activities, we will further explore the anti-infective prospects of these compounds in chronic wounds and expect to find promising drug candicates. And the structure-activity relationships of the synthetic cajaninstilbene acid analogues against resistant bacterial infection will be revealed throughout a comprehensive research. This study will provide an important scientific basis for drug design of antibacterial agents against drug-resistant bacterial infection.