Design, Synthesis, and Structure–Activity Optimization of Marine-Inspired Macrolactones as Nanomolar Anticancer Agents
Inspired by the anticancer marine natural product superstolide A, we previously designed and synthesized a truncated analogue, designated ZJ-101, that retains the potent anticancer activity of the original natural product. In this study, using ZJ-101 as a lead compound, we conducted molecular design, convergent synthesis, and structure–activity optimization, resulting in the discovery of new analogues exhibiting anticancer activity approximately 30–80-fold more potent than ZJ-101, with IC50 values predominantly in the single-digit nanomolar range.
Authors
- Shan Qian (ORCID: https://orcid.org/0000-0002-9550-6885)
- J Liu
- Sarah A. Head (ORCID: https://orcid.org/0000-0002-8942-7785)
- Phillip R. Sanchez (ORCID: https://orcid.org/0000-0002-6354-0368)
- Ruth Hartke
- Wei Zheng (ORCID: https://orcid.org/0000-0003-1226-070X)
- Zhendong Jin (ORCID: https://orcid.org/0000-0003-1672-513X)
- Haibo Qiu
Institutions
- University of Iowa (US)
- National Institutes of Health (US)
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- National Center for Advancing Translational Sciences (US)
Publication Details
- Journal
- ACS Medicinal Chemistry Letters
- Published
- 2026-05-16
- DOI
- https://doi.org/10.1021/acsmedchemlett.6c00222
- Primary Topic
- Marine Sponges and Natural Products
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Flight Attendant Medical Research Institute
- National Cancer Institute
- National Center for Advancing Translational Sciences