Cover image for Vol. 10 Issue 4

Editor-in-Chief: Natalia Ortúzar

Impact Factor: 3.046

ISI Journal Citation Reports © Ranking: 2013: 18/58 (Chemistry Medicinal); 75/256 (Pharmacology & Pharmacy)

Online ISSN: 1860-7187

Associated Title(s): Angewandte Chemie International Edition, Chemistry - A European Journal, Chemistry – An Asian Journal, ChemBioChem, Medicinal Research Reviews, Molecular Informatics

February 14, 2013

VIP: Optimization of the Marine Triterpene Sipholenols as Inhibitors of Breast Cancer Migration and Invasion

VIP: Optimization of the Marine Triterpene Sipholenols as Inhibitors of Breast Cancer Migration and InvasionAhmed I. Foudah, Sandeep Jain, Belnaser Busnena, Khalid A. El Sayed

Marine natural products are among the most important resources for anticancer drug discovery. The marine-sponge-derived triterpene sipholenols can inhibit the migration and invasion of breast cancer cells, impeding their expected metastasis. Several sipholenol derivatives were prepared in order to improve their activity. Breast tumor kinase (Brk), also known as protein tyrosine kinase 6 (PTK6), was identified as a possible molecular target of sipholenols. Overexpressed Brk acts as a mediator of cancer cell phenotypes, inducing their proliferation, survival, and migration. Inhibition of Brk activity provides a new approach toward sensitizing tumor cells to other chemotherapeutics and controlling the metastasis of breast cancer.

A collaborative research effort led by Dr. El Sayed and colleagues at the University of Louisiana at Monroe (USA) has revealed sipholenol analogues as novel scaffolds for drugs that inhibit breast cancer cell migration and invasion. By using a combination of high-throughput screening, spectroscopic analysis, and subsequent modification of initial hits, the team was able to generate a series of active entities. Their results show the potential of these compounds to act as potent and selective inhibitors of Brk activity, with the potential for use in controlling Brk-dependent metastatic malignancies.

Received November 6, 2012; published online February 12, 2013, DOI: 10.1002/cmdc.201200516.

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