Insights into the structure-activity relationship of the anticancer compound ZJ-101, a derivative of marine natural product superstolide A: A role played by the lactone moiety.
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-109 was designed and synthesized to probe the importance of the lactone moiety of the molecule by replacing the lactone in ZJ-101 with a lactam. The biological evaluation showed that ZJ-109 is about 8-12 times less active against cancer cells in vitro than ZJ-101, suggesting that the lactone moiety of the molecule is important for its anticancer activity.
Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA.
Haibo
H
Qiu
Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA.
Shan
S
Qian
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe St., Baltimore, MD 21205, USA.
Sarah A
SA
Head
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.
Jun O
JO
Liu
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.
Zhendong
Z
Jin
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018942:Macrolides; D013764:Tetrahydronaphthalenes; C000621213:ZJ-101
Anticancer agent; Asymmetric synthesis; Drug design; Structure–activity relationship; Superstolide A analog