Insights into the structure-activity relationship of the anticancer compound ZJ-101, a derivative of marine natural product superstolide A: A critical role played by the conjugated trienyl lactone moiety

Shan Qian; Aashay K Shah; Sarah A Head; Jun O Liu; Zhendong Jin

doi:10.1016/j.bmcl.2016.06.057

Insights into the structure-activity relationship of the anticancer compound ZJ-101, a derivative of marine natural product superstolide A: A critical role played by the conjugated trienyl lactone moiety

Bioorg Med Chem Lett. 2016 Aug 1;26(15):3411-3. doi: 10.1016/j.bmcl.2016.06.057. Epub 2016 Jun 22.

Authors

Shan Qian¹, Aashay K Shah¹, Sarah A Head², Jun O Liu³, Zhendong Jin⁴

Affiliations

¹ Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA.
² Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe St., Baltimore, MD 21205, USA.
³ Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe St., Baltimore, MD 21205, USA; Department of Onocology, Johns Hopkins University School of Medicine, 725 North Wolfe St., Baltimore, MD 21205, USA.
⁴ 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.

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, two new analogs, ZJ-105 and ZJ-106, were designed and synthesized to probe the importance of the conjugated trienyl lactone moiety of the molecule by replacing the C2-C3 double bond in ZJ-101 with a single bond and switching the geometry of the C4-C5 double bond in ZJ-101 from Z to E, respectively. Biological evaluation showed that ZJ-105 completely loses antiproliferative activity whereas ZJ-106 is significantly less active against cancer cells in vitro than ZJ-101, suggesting that the conjugated trienyl lactone moiety of the molecule is critical for its anticancer activity.

Keywords: Anticancer agent; Asymmetric synthesis; Drug design; Structure–activity relationship; Superstolide A analog.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / isolation & purification
Antineoplastic Agents / pharmacology*
Biological Products / chemistry
Biological Products / isolation & purification
Biological Products / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Lactones / chemistry
Lactones / pharmacology*
Macrolides / chemistry
Macrolides / isolation & purification
Macrolides / pharmacology*
Molecular Structure
Porifera / chemistry*
Structure-Activity Relationship
Tetrahydronaphthalenes / chemistry
Tetrahydronaphthalenes / isolation & purification
Tetrahydronaphthalenes / pharmacology*

Substances

Antineoplastic Agents
Biological Products
Lactones
Macrolides
Tetrahydronaphthalenes
ZJ-101

Grants and funding

R21 CA204836/CA/NCI NIH HHS/United States