Quorum Sensing Laboratory, Centre for Research in Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, India.
Organometallics and Catalysis Laboratory, Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India.
Front Cell Infect Microbiol. 2024 Jan 15;13:1340135. doi: 10.3389/fcimb.2023.1340135. eCollection 2023.
leads to diverse infections, and their treatment relies on the use of antibiotics. Nevertheless, the rise of antibiotic resistance poses an escalating challenge and various mechanisms contribute to antibiotic resistance, including modifications to drug targets, enzymatic deactivation of drugs, and increased efflux of antibiotics. Hence, the quest for innovative antimicrobial solutions has intensified in the face of escalating antibiotic resistance and the looming threat of superbugs. The NorA protein of , classified as an efflux pump within the major facilitator superfamily, when overexpressed, extrudes various substances, including fluoroquinolones (such as ciprofloxacin) and quaternary ammonium. Addressing this, the unexplored realm of inorganic and organometallic compounds in medicinal chemistry holds promise. Notably, the study focused on investigating two different series of palladium-based metal complexes consisting of QSL_P and QSL_P ligands to identify a potent NorA efflux pump inhibitor that can restore the susceptibility to fluoroquinolone antibiotics. QSL_Pd was identified as a potent efflux pump inhibitor from the real-time efflux assay. QSL_Pd also resensitized SA1199B to ciprofloxacin at a low concentration of 0.125 µg/mL without elucidating cytotoxicity on the NRK-62E cell line. The findings were substantiated by docking results, indicating favorable interactions between QSL_Pd and the NorA efflux pump.
导致多种感染，其治疗依赖于抗生素的使用。然而，抗生素耐药性的上升带来了日益严峻的挑战，各种机制导致了抗生素耐药性，包括药物靶标修饰、药物酶失活和抗生素外排增加。因此，面对抗生素耐药性的不断升级和超级细菌的威胁，人们加紧寻找创新的抗菌解决方案。 属于主要易化子超家族中的外排泵，当过度表达时，会排出包括氟喹诺酮类（如环丙沙星）和季铵盐在内的各种物质。针对这一点，药物化学中无机和有机金属化合物的未探索领域具有很大的潜力。值得注意的是，这项研究专注于研究两种不同系列的钯基金属配合物，这些配合物由 QSL_P 和 QSL_P 配体组成，目的是确定一种有效的 NorA 外排泵抑制剂，以恢复对氟喹诺酮类抗生素的敏感性。 QSL_Pd 被鉴定为实时外排测定中的有效外排泵抑制剂。QSL_Pd 还能以低浓度 0.125 µg/mL 使 SA1199B 对环丙沙星重新敏感，而对 NRK-62E 细胞系没有阐明细胞毒性。对接结果证实了这一发现，表明 QSL_Pd 与 NorA 外排泵之间存在有利的相互作用。
