title: Developing piperlongumine-directed glutathione S-transferase inhibitors by an electrophilicity-based strategy.
abstract: We report a case of successful design of glutathione S-transferase (GST) inhibitors via a natural product-inspired and electrophilicity-based strategy. Based on this strategy, a novel piperlongumine analog (PL-13) bearing a para-trifluoromethyl group and an α-chlorine on its aromatic and lactam rings, respectively, surfaced as a promising GST inhibitor, thereby overcoming cisplatin resistance in lung cancer A549 cells.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu 730000, China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu 730000, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu 730000, China.
authors.forename: Jia-Fang
authors.initials: JF
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu 730000, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu 730000, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu 730000, China. Electronic address: bozhou@lzu.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000072283:A549 Cells; D002945:Cisplatin; D004148:Dioxolanes / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D006801:Humans; D010881:Piperidones
chemical_list: D002945:Cisplatin; D004148:Dioxolanes; D004791:Enzyme Inhibitors; D005982:Glutathione Transferase; C498077:piperlongumine; D010881:Piperidones
keywords: Electrophilicity; Glutathione S-transferases; Multiple drug resistance; Piperlongumine