title: Insights into the structure-activity relationship of the anticancer compound ZJ-101: A critical role played by the cyclohexene ring.
abstract: Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure-activity relationship study, a new analog ZJ-102 was designed and synthesized to probe the importance of the cyclohexenyl group through its replacement to a phenyl group using a concise and convergent synthetic approach. The biological evaluation showed that this new analog ZJ-102 is significantly less active against cancer cells in vitro than ZJ-101, suggesting that the cyclohexenyl ring (along with its two stereogenic centers) present in ZJ-101 is important for its anticancer activity.
authors.affiliation: Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Aashay K
authors.initials: AK
authors.lastname: Shah
authors.affiliation: Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Qian
authors.affiliation: Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe St., Baltimore, MD 21205, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Head
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe St., Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, 725 North Wolfe St., Baltimore, MD 21205, USA.
authors.forename: Jun O
authors.initials: JO
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA. Electronic address: zhendong-jin@uiowa.edu.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Jin
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053138:Cyclohexenes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D053138:Cyclohexenes; D018942:Macrolides; D013764:Tetrahydronaphthalenes; C000621213:ZJ-101; C052568:cyclohexene
keywords: Anticancer agent; Asymmetric synthesis; Drug design; Structure–activity relationship; Superstolide A analog