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Updated: Jul 14, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Antitumor agents 259. Design, syntheses, and structure-activity relationship study of desmosdumotin C analogs
Kyoko Nakagawa-Goto1, Tzu-Hsuan Chen, Chieh-Yu Peng
1Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Abstract:
Desmosdumotin C (1) and its analogs previously showed potent, selective in vitro anticancer activity. To explore structure-activity relationships of 1 and further increase potency and selectivity, 15 novel analogs (7-15 and 21-26) were synthesized and evaluated for cytotoxity against several human tumor cell lines, as well as inhibition of human endothelial (HUVEC) replication. 4-Bromo-3',3',5'-tripropyl analog 26 showed significant cytotoxity against A549, A431, 1A9, and HCT-8 with ED50 values of 1.0, 1.2, 0.9, and 1.3 mug/mL, respectively. Compound 26 also strongly inhibited the growth of matched tumor cells, KB-VIN and its parent cell KB. Furthermore, analogs 13 and 21 were over 5-fold more potent against KB-VIN than KB. Bromination of ring-B and tripropyl functionalization of ring-A enhanced activity, while alkylation of ring-B promoted KB-VIN/KB selectivity. 2-Furyl analog 16 showed selective activity against HUVEC, suggesting that it may have potential as a new prototype for angiogenesis inhibition.
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