Department of Microbiology, Panjab University, Chandigarh, India.
Department of Applied Sciences, Punjab Engineering College (Deemed to be University), Chandigarh, India.
Drug Dev Res. 2021 Jun;82(4):605-615. doi: 10.1002/ddr.21781. Epub 2021 Jan 4.
In this article, we report the chemical synthesis of pyochelin-zingerone conjugate via a hydrolysable ester linkage for drug delivery as a "Trojan Horse Strategy." It is a new therapeutic approach to combat microbial infection and to address the issue of multi drug resistance in Gram-negative, nosocomial pathogen Pseudomonas aeruginosa. Pyochelin (Pch) is a catecholate type of phenolate siderophore produced and utilized by the pathogen P. aeruginosa to assimilate iron when colonizing the vertebrate host. Zingerone, is active component present in ginger, a dietary herb known for its anti-virulent approach against P. aeruginosa. In the present study, zingerone was exploited to act as a good substitute for existing antibiotics, known to have developed resistance by most pathogens. Encouraging results were obtained by docking analysis of pyochelin-zingerone conjugate with FptA, the outer membrane receptor of pyochelin. Conjugate also showed anti-quorum sensing activity and also inhibited swimming, swarming, and twitching motilities as well as biofilm formation in vitro.
本文报道了一种通过可水解酯键将吡咯并苯并二氮卓-肉桂醇缀合物用于药物输送的化学合成方法，作为一种“特洛伊木马策略”。这是一种对抗微生物感染和解决革兰氏阴性、医院病原体铜绿假单胞菌多药耐药问题的新治疗方法。吡咯并苯并二氮卓（Pch）是一种由病原体铜绿假单胞菌产生和利用的儿茶酚型酚盐类铁载体，在定殖脊椎动物宿主时用于摄取铁。肉桂醇是姜中的一种活性成分，姜是一种饮食草本植物，以其针对铜绿假单胞菌的抗毒作用而闻名。在本研究中，肉桂醇被用作现有抗生素的替代品，大多数病原体对现有抗生素已经产生了耐药性。通过与外膜受体 FptA 的对接分析，吡咯并苯并二氮卓-肉桂醇缀合物得到了令人鼓舞的结果。该缀合物还表现出抗群体感应活性，并且还抑制体外的游泳、群集和蠕动运动以及生物膜形成。
