marine drugs Article The Maxi-K (BK) Channel Antagonist Penitrem A as a Novel Breast Cancer-Targeted Therapeutic Amira A. Goda 1, Abu Bakar Siddique 1 ID , Mohamed Mohyeldin 1,3, Nehad M. Ayoub 2 ID and Khalid A. El Sayed 1,* ID 1 Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA;
[email protected] (A.A.G.);
[email protected] (A.B.S.);
[email protected] (M.M.) 2 Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan;
[email protected] 3 Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt * Correspondence:
[email protected]; Tel.: +1-318-342-1725 Received: 6 April 2018; Accepted: 9 May 2018; Published: 11 May 2018 Abstract: Breast cancer (BC) is a heterogeneous disease with different molecular subtypes. The high conductance calcium-activated potassium channels (BK, Maxi-K channels) play an important role in the survival of some BC phenotypes, via membrane hyperpolarization and regulation of cell cycle. BK channels have been implicated in BC cell proliferation and invasion. Penitrems are indole diterpene alkaloids produced by various terrestrial and marine Penicillium species. Penitrem A (1) is a selective BK channel antagonist with reported antiproliferative and anti-invasive activities against multiple malignancies, including BC. This study reports the high expression of BK channel in different BC subtypes. In silico BK channel binding affinity correlates with the antiproliferative activities of selected penitrem analogs. 1 showed the best binding fitting at multiple BK channel crystal structures, targeting the calcium-sensing aspartic acid moieties at the calcium bowel and calcium binding sites.