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Design, Synthesis, and Structure-Activity Optimization of Marine-Inspired Macrolactones as Nanomolar Anticancer
Shan Qian1, Haibo Qiu1, Phillip R Sanchez2
1Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa 52242, United States.
Abstract:
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.
