Boholamide A, an APD-Class, Hypoxia-Selective Cyclodepsipeptide. J Nat Prod 2020 Apr 24;83(4):1249-1257
Date
03/19/2020Pubmed ID
32186874Pubmed Central ID
PMC10172148DOI
10.1021/acs.jnatprod.0c00038Scopus ID
2-s2.0-85082040097 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
Calcium homeostasis is implicated in some cancers, leading to the possibility that selective control of calcium might lead to new cancer drugs. On the basis of this idea, we designed an assay using a glioblastoma cell line and screened a collection of 1000 unique bacterial extracts. Isolation of the active compound from a hit extract led to the identification of boholamide A (1), a 4-amido-2,4-pentadieneoate (APD)-class peptide. Boholamide A (1) applied in the nanomolar range induces an immediate influx of Ca2+ in glioblastoma and neuronal cells. APD-class natural products are hypoxia-selective cytotoxins that primarily target mitochondria. Like other APD-containing compounds, 1 is hypoxia selective. Since APD natural products have received significant interest as potential chemotherapeutic agents, 1 provides a novel APD scaffold for the development of new anticancer compounds.
Author List
Torres JP, Lin Z, Fenton DS, Leavitt LU, Niu C, Lam PY, Robes JM, Peterson RT, Concepcion GP, Haygood MG, Olivera BM, Schmidt EWAuthor
Pui Ying Lam PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antineoplastic AgentsBiological Products
Calcium
Cytotoxins
Depsipeptides
Hypoxia
Molecular Structure
Neoplasms
