TY - JOUR
T1 - Insights into the structure–activity relationship of the anticancer compound ZJ-101, a derivative of marine natural product superstolide A
T2 - A critical role played by the conjugated trienyl lactone moiety
AU - Qian, Shan
AU - Shah, Aashay K.
AU - Head, Sarah A.
AU - Liu, Jun O.
AU - Jin, Zhendong
N1 - Funding Information:
This work was made possible by the generous support of the GAP funding from the Office of the Vice President for Research and Economic Development (OVPRED) at the University of Iowa and funding from InnoBioPharma , LLC (D2015070002). Aashay K. Shah was supported by a fellowship from the University of Iowa Center for Biocatalysis and Bioprocessing , and by activities of the Predoctoral Training program in Biotechnology, NIH grant 2T32GM008365 . Special thanks are due to the Graduate College and College of Pharmacy at the University of Iowa for providing a dissertation fellowship to Aashay K. Shah.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Anticancer agent
KW - Asymmetric synthesis
KW - Drug design
KW - Structure–activity relationship
KW - Superstolide A analog
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U2 - 10.1016/j.bmcl.2016.06.057
DO - 10.1016/j.bmcl.2016.06.057
M3 - Article
C2 - 27374243
AN - SCOPUS:84978811095
SN - 0960-894X
VL - 26
SP - 3411
EP - 3413
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 15
ER -