Analogues of the marine alkaloids oroidin, clathrodin, and hymenidin induce apoptosis in human HepG2 and THP-1 cancer cells

作者：Tomasic Tihomir; Nabergoj Dominik; Vrbek Sanja; Zidar Nace; Jakopin Ziga; Zula Ales; Hodnik Ziga; Jukic Marko; Anderluh Marko; Ilas Janez; Dolenc Marija Sollner; Peluso Jean; Ubeaud Sequier Genevieve; Muller Christian D^*; Masic Lucija Peterlin; Kikelj Danijel

来源：Medchemcomm, 2015, 6(1): 105-110.

DOI：10.1039/c4md00286e

The marine alkaloids clathrodin, oroidin, and hymenidin, which were isolated from Agelas sponges, possess diverse biological activities. Herein, we describe the design of a library of their analogues and the evaluation of their apoptosis-inducing activities against the human hepatocellular carcinoma HepG2 and acute monocytic leukaemia THP-1 cell lines. The screening of the complete library of 96 compounds using the HepG2 cell line allowed us to determine key structural elements and physicochemical properties that are responsible for the apoptosis-inducing activity. The indole-based compounds 24c, 28c, 29c, and 34c were found to be the most potent inducers of apoptosis in HepG2 and THP-1 cell lines with EC50 values in the low micromolar range. Cell cycle analysis assays confirmed that compounds 24c, 28c, 29c, and 34c induce the apoptosis of THP-1 cells at 25 mu M, which highlights these oroidin analogues as interesting candidates for further evaluation of their anticancer activity.

• 出版日期2015